Role of the Insulin-like growth factor axis and the Transforming growth factor-β in the regulation of the placenta and the pathogenesis of Gestational Trophoblastic Diseases
Main Article Content
Adriana Umana-Perez
http://orcid.org/0000-0001-9262-2699
Susana Novoa-Herran
http://orcid.org/0000-0003-2157-1008
Juan Jose Castro
http://orcid.org/0000-0002-7107-1303
Andres Correa-Sanchez
http://orcid.org/0000-0003-1423-3449
Valentina Guevara
http://orcid.org/0000-0003-1535-615X
David Alejandro Lopez-Gonzalez
http://orcid.org/0000-0003-3091-9950
Myriam Sanchez-Gomez
http://orcid.org/0000-0001-9262-2699
Susana Novoa-Herran
http://orcid.org/0000-0003-2157-1008
Juan Jose Castro
http://orcid.org/0000-0002-7107-1303
Andres Correa-Sanchez
http://orcid.org/0000-0003-1423-3449
Valentina Guevara
http://orcid.org/0000-0003-1535-615X
David Alejandro Lopez-Gonzalez
http://orcid.org/0000-0003-3091-9950
Myriam Sanchez-Gomez
Abstract
During human pregnancy, the trophoblast develops as the fetal compartment, while in bidirectional communication with the maternal decidua. The trophoblast is responsible for the adequate implantation of the embryo, supply of nutrients and environmental protection of the fetus along the progress of pregnancy. To perform these functions trophoblast cells, undergo a complex and finely tuned differentiation into specialized groups of cells, in a process regulated by several hormones, growth factors and cytokines. Abnormalities in trophoblast function result in several pregnancy complications.
In this review, we focus our attention on two growth factors with pivotal roles during human pregnancy. The Insulin-like growth factor (IGF) family and the Transforming growth factor (TGF-β) axis are important regulators of the proliferation, differentiation, apoptosis, migration and invasion of human trophoblasts. We summarize what is described in the literature on how these factors and their receptors are expressed on the different subsets of trophoblasts, the signaling pathways that transduce their corresponding actions and functional biological effects. We describe the associations that have been found between these growth factors and the group of pathologies known as Gestational Trophoblastic Diseases (GTD).
Keywords:
Trophoblasts, Placenta, Transforming Growth Factor beta, Insulin-Like Growth Factor I, Insulin-Like Growth Factor II, GTD
Article Details
How to Cite
UMANA-PEREZ, Adriana et al.
Role of the Insulin-like growth factor axis and the Transforming growth factor-β in the regulation of the placenta and the pathogenesis of Gestational Trophoblastic Diseases.
Medical Research Archives, [S.l.], v. 8, n. 10, oct. 2020.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2247>. Date accessed: 21 dec. 2024.
doi: https://doi.org/10.18103/mra.v8i10.2247.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Staun-Ram E, Shalev E. Human trophoblast function during the implantation process. Reproductive Biology and Endocrinology. 2005;3(1):56. DOI: https://doi.org/10.1186/1477-7827-3-56
2. Vlahos A, Mansell T, Saffery R, Novakovic B. Human placental methylome in the interplay of adverse placental health, environmental exposure, and pregnancy outcome. PLoS Genet. 2019;15(8):e1008236. DOI: https://doi.org/10.1371/journal.pgen.1008236
3. Lindhard A, Bentin-Ley U, Ravn V, et al. Biochemical evaluation of endometrial function at the time of implantation. 2002;78(2):221-233. DOI: https://doi.org//10.1016/S0015-0282(02)03240-5
4. Armant DR. Blastocysts don't go it alone. Extrinsic signals fine-tune the intrinsic developmental program of trophoblast cells. Developmental biology. 2005;280(2):260-280. DOI: https://doi.org/10.1016/j.ydbio.2005.02.009
5. Carter AM, Enders AC, Pijnenborg R. The role of invasive trophoblast in implantation and placentation of primates. Philosophical transactions of the Royal Society of London Series B, Biological sciences. 2015;370(1663):20140070. DOI: https://doi.org/10.1098/rstb.2014.0070
6. Cross JC, Werb Z, Fisher SJ. Implantation and the placenta: key pieces of the development puzzle. Science. 1994;266(5190):1508-1518. DOI: https://doi.org/10.1126/science.7985020
7. Jansson T, Powell TL. IFPA 2005 Award in Placentology Lecture. Human placental transport in altered fetal growth: does the placenta function as a nutrient sensor? -- a review. Placenta. 2006;27 Suppl A:S91-97. DOI: 10.1016/j.placenta.2005.11.010
8. Ferretti C, Bruni L, Dangles-Marie V, Pecking AP, Bellet D. Molecular circuits shared by placental and cancer cells, and their implications in the proliferative, invasive and migratory capacities of trophoblasts. Hum Reprod Update. 2007;13(2):121-141. DOI: https://doi.org/10.1093/humupd/dml048
9. Poste G, Fidler IJ. The pathogenesis of cancer metastasis. Nature. 1980;283(5743):139-146. DOI: https://doi.org/10.1038/283139a0
10. Weiss G, Sundl M, Glasner A, Huppertz B, Moser G. The trophoblast plug during early pregnancy: a deeper insight. Histochem Cell Biol. 2016;146(6):749-756. DOI: https://doi.org/10.1007/s00418-016-1474-z
11. Moser G, Windsperger K, Pollheimer J, de Sousa Lopes SC, Huppertz B. Human trophoblast invasion: new and unexpected routes and functions. Histochem Cell Biol. 2018;150(4):361-370. DOI: https://doi.org/10.1007/s00418-018-1699-0
12. Moser G, Gauster M, Orendi K, Glasner A, Theuerkauf R, Huppertz B. Endoglandular trophoblast, an alternative route of trophoblast invasion? Analysis with novel confrontation co-culture models. Hum Reprod. 2010;25(5):1127-1136. DOI: https://doi.org/10.1093/humrep/deq035
13. Huppertz B, Weiss G, Moser G. Trophoblast invasion and oxygenation of the placenta: measurements versus presumptions. J Reprod Immunol. 2014;101-102:74-79. DOI: https://doi.org/10.1016/j.jri.2013.04.003
14. Chakraborty C, Gleeson LM, McKinnon T, Lala PK. Regulation of human trophoblast migration and invasiveness. Can J Physiol Pharmacol. 2002;80(2):116-124. DOI: https://doi.org/10.1139/y02-016
15. LeRoith D, Roberts CT, Jr. The insulin-like growth factor system and cancer. Cancer Lett. 2003;195(2):127-137. DOI: https://doi.org/10.1016/s0304-3835(03)00159-9
16. LeRoith D, Werner H, Neuenschwander S, Kalebic T, Helman LJ. The role of the insulin-like growth factor-I receptor in cancer. Ann N Y Acad Sci. 1995;766:402-408. DOI: https://doi.org/10.1111/j.1749-6632.1995.tb26689.x
17. Samani AA, Yakar S, LeRoith D, Brodt P. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr Rev. 2007;28(1):20-47. DOI: https://doi.org/10.1210/er.2006-0001
18. Belfiore A, Frasca F, Pandini G, Sciacca L, Vigneri R. Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease. Endocr Rev. 2009;30(6):586-623. DOI: https://doi.org/10.1210/er.2008-0047
19. Pandini G, Frasca F, Mineo R, Sciacca L, Vigneri R, Belfiore A. Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved. J Biol Chem. 2002;277(42):39684-39695. DOI: https://doi.org/10.1074/jbc.M202766200
20. El-Shewy HM, Luttrell LM. Insulin-like growth factor-2/mannose-6 phosphate receptors. Vitamins and hormones. 2009;80:667-697. DOI: https://doi.org/10.1016/S0083-6729(08)00624-9
21. Han VK, Bassett N, Walton J, Challis JR. The expression of insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) genes in the human placenta and membranes: evidence for IGF-IGFBP interactions at the feto-maternal interface. J Clin Endocrinol Metab. 1996;81(7):2680-2693. DOI: https://doi.org/10.1210/jcem.81.7.8675597
22. Holmes R, Porter H, Newcomb P, Holly JM, Soothill P. An immunohistochemical study of type I insulin-like growth factor receptors in the placentae of pregnancies with appropriately grown or growth restricted fetuses. Placenta. 1999;20(4):325-330. DOI: https://doi.org/10.1053/plac.1998.0387
23. Forbes K, Westwood M, Baker PN, Aplin JD. Insulin-like growth factor I and II regulate the life cycle of trophoblast in the developing human placenta. American journal of physiology Cell physiology. 2008;294(6):C1313-1322. DOI: https://doi.org/10.1152/ajpcell.00035.2008
24. Kooijman R. Regulation of apoptosis by insulin-like growth factor (IGF)-I. Cytokine Growth Factor Rev. 2006;17(4):305-323. DOI: https://doi.org/10.1016/j.cytogfr.2006.02.002
25. Forbes K, Shah VK, Siddals K, Gibson JM, Aplin JD, Westwood M. Statins inhibit insulin-like growth factor action in first trimester placenta by altering insulin-like growth factor 1 receptor glycosylation. Mol Hum Reprod. 2015;21(1):105-114. DOI: https://doi.org/10.1093/molehr/gau093
26. Constancia M, Hemberger M, Hughes J, et al. Placental-specific IGF-II is a major modulator of placental and fetal growth. Nature. 2002;417(6892):945-948. DOI: https://doi.org/10.1038/nature00819
27. Buckberry S, Bianco-Miotto T, Hiendleder S, Roberts CT. Quantitative allele-specific expression and DNA methylation analysis of H19, IGF2 and IGF2R in the human placenta across gestation reveals H19 imprinting plasticity. PLoS One. 2012;7(12):e51210. DOI: https://doi.org/10.1371/journal.pone.0051210
28. Fang J, Furesz TC, Lurent RS, Smith CH, Fant ME. Spatial polarization of insulin-like growth factor receptors on the human syncytiotrophoblast. Pediatric research. 1997;41(2):258-265. DOI: https://doi.org/10.1203/00006450-199702000-00017
29. El-Shewy HM, Johnson KR, Lee M-H, Jaffa AA, Obeid LM, Luttrell LM. Insulin-like growth factors mediate heterotrimeric G protein-dependent ERK1/2 activation by transactivating sphingosine 1-phosphate receptors. The Journal of biological chemistry. 2006;281(42):31399-31407. DOI: https://doi.org/10.1074/jbc.M605339200
30. McKinnon T, Chakraborty C, Gleeson LM, Chidiac P, Lala PK. Stimulation of human extravillous trophoblast migration by IGF-II is mediated by IGF type 2 receptor involving inhibitory G protein(s) and phosphorylation of MAPK. The Journal of clinical endocrinology and metabolism. 2001;86(8):3665-3674. DOI: https://doi.org/10.1210/jcem.86.8.7711
31. Brown J, Delaine C, Zaccheo OJ, et al. Structure and functional analysis of the IGF-II/IGF2R interaction. EMBO J. 2008;27(1):265-276. DOI: https://doi.org/10.1038/sj.emboj.7601938
32. Speroff L, Fritz Marc A. The Endocrinology of Pregnancy. Clinical Gynecologic Endocrinology and Fertility. Seventh Ed. ed. Philadelphia, USA: Lippincott Williams & Wilkins; 2005:287.
33. Baumann MU, Schneider H, Malek A, et al. Regulation of human trophoblast GLUT1 glucose transporter by insulin-like growth factor I (IGF-I). PLoS One. 2014;9(8):e106037. DOI: https://doi.org/10.1371/journal.pone.0106037
34. Bajoria R, Sooranna SR, Ward S, Hancock M. Placenta as a link between amino acids, insulin-IGF axis, and low birth weight: evidence from twin studies. J Clin Endocrinol Metab. 2002;87(1):308-315. DOI: https://doi.org/10.1210/jcem.87.1.8184
35. Magnusson-Olsson AL, Hamark B, Ericsson A, Wennergren M, Jansson T, Powell TL. Gestational and hormonal regulation of human placental lipoprotein lipase. J Lipid Res. 2006;47(11):2551-2561. DOI: https://doi.org/10.1194/jlr.M600098-JLR200
36. Baxter RC. Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities. Am J Physiol Endocrinol Metab. 2000;278(6):E967-976. DOI: https://doi.org/10.1152/ajpendo.2000.278.6.E967
37. Hamilton GS, Lysiak JJ, Han VK, Lala PK. Autocrine-paracrine regulation of human trophoblast invasiveness by insulin-like growth factor (IGF)-II and IGF-binding protein (IGFBP)-1. Experimental cell research. 1998;244(1):147-156. DOI: https://doi.org/10.1006/excr.1998.4195
38. Asvold BO, Eskild A, Jenum PA, Vatten LJ. Maternal concentrations of insulin-like growth factor I and insulin-like growth factor binding protein 1 during pregnancy and birth weight of offspring. Am J Epidemiol. 2011;174(2):129-135. DOI: https://doi.org/10.1093/aje/kwr067
39. Sifakis S, Akolekar R, Kappou D, Mantas N, Nicolaides KH. Maternal serum insulin-like growth factor-I at 11-13 weeks in preeclampsia. Prenat Diagn. 2010;30(11):1026-1031. DOI: https://doi.org/10.1002/pd.2555
40. Irving JA, Lala PK. Functional role of cell surface integrins on human trophoblast cell migration: regulation by TGF-beta, IGF-II, and IGFBP-1. Exp Cell Res. 1995;217(2):419-427. DOI: https://doi.org/10.1006/excr.1995.1105
41. Chakraborty C, Barbin YP, Chakrabarti S, Chidiac P, Dixon SJ, Lala PK. Endothelin-1 promotes migration and induces elevation of [Ca2+]i and phosphorylation of MAP kinase of a human extravillous trophoblast cell line. Mol Cell Endocrinol. 2003;201(1-2):63-73. DOI: https://doi.org/10.1016/s0303-7207(02)00431-8
42. Novoa Herrán S, Sanchez-Gomez M. El IGF-II estimula la actividad de MMP-9 y MMP-2 en un modelo de trofoblasto humano. Acta Biológica Colombiana. 2011;16:121-132. https://revistas.unal.edu.co/index.php/actabiol/article/view/15816/28142
43. Pardali K, Moustakas A. Actions of TGF-beta as tumor suppressor and pro-metastatic factor in human cancer. Biochim Biophys Acta. 2007;1775(1):21-62. DOI: https://doi.org/10.1016/j.bbcan.2006.06.004
44. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 2003;113(6):685-700. DOI: https://doi.org/10.1016/s0092-8674(03)00432-x
45. Schmierer B, Hill CS. TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility. Nat Rev Mol Cell Biol. 2007;8(12):970-982. DOI: https://doi.org/10.1038/nrm2297
46. Vuckovic M, Genbacev O, Kumar S. Immunohistochemical localisation of transforming growth factor-beta in first and third trimester human placenta. Pathobiology. 1992;60(3):149-151. DOI: https://doi.org/10.1159/000163714
47. Xuan YH, Choi YL, Shin YK, et al. Expression of TGF-beta signaling proteins in normal placenta and gestational trophoblastic disease. Histol Histopathol. 2007;22(3):227-234. DOI: https://doi.org/10.14670/HH-22.227
48. Karmakar S, Das C. Regulation of trophoblast invasion by IL-1beta and TGF-beta1. Am J Reprod Immunol. 2002;48(4):210-219. DOI: https://doi.org/10.1034/j.1600-0897.2002.01151.x
49. Graham CH, Lala PK. Mechanism of control of trophoblast invasion in situ. J Cell Physiol. 1991;148(2):228-234. DOI: https://doi.org/10.1002/jcp.1041480207
50. Graham CH, Lysiak JJ, McCrae KR, Lala PK. Localization of transforming growth factor-beta at the human fetal-maternal interface: role in trophoblast growth and differentiation. Biol Reprod. 1992;46(4):561-572. DOI: https://doi.org/10.1095/biolreprod46.4.561
51. Hernandez-Valencia M, Zarate A, Ochoa R, Fonseca ME, Amato D, De Jesus Ortiz M. Insulin-like growth factor I, epidermal growth factor and transforming growth factor beta expression and their association with intrauterine fetal growth retardation, such as development during human pregnancy. Diabetes, Obesity and Metabolism. 2001;3(6):457-462. DOI: https://doi.org/10.1046/j.1463-1326.2001.00168.x
52. Singh M, Orazulike NC, Ashmore J, Konje JC. Changes in maternal serum transforming growth factor beta-1 during pregnancy: a cross-sectional study. Biomed Res Int. 2013;2013:318464. DOI: https://doi.org/10.1155/2013/318464
53. Graham CH, Lysiak JJ, McCrae KR, Lala PK. Localization of Transforming Growth Factor-β at the Human Fetal-Maternal Interface: Role in Trophoblast Growth and Differentiation1. Biology of Reproduction. 1992;46(4):561-572. DOI: https://doi.org/10.1095/biolreprod46.4.561
54. Morrish DW, Bhardwaj D, Paras MT. Transforming growth factor beta 1 inhibits placental differentiation and human chorionic gonadotropin and human placental lactogen secretion. Endocrinology. 1991;129(1):22-26. DOI: https://doi.org/10.1210/endo-129-1-22
55. Song Y, Keelan J, France JT. Activin-A stimulates, while transforming growth factor β1 inhibits,chorionic gonadotrophin production and aromatase activity in cultured human placental trophoblasts. Placenta. 1996;17(8):603-610. DOI: https://doi.org/10.1016/S0143-4004(96)80078-6
56. Luo S, Yu H, Wu D, Peng C. Transforming growth factor-beta1 inhibits steroidogenesis in human trophoblast cells. Mol Hum Reprod. 2002;8(4):318-325. DOI: https://doi.org/10.1093/molehr/8.4.318
57. Meisser A, Chardonnens D, Campana A, Bischof P. Effects of tumour necrosis factor-α, interleukin-1 α, macrophage colony stimulating factor and transforming growth factor β on trophoblastic matrix metalloproteinases. Molecular Human Reproduction. 1999;5(3):252-260. DOI: http://dx.doi.org/10.1093/molehr/5.3.252
58. Richard CA, Jones JM, DeLoia JA. Comparison of cell cycle regulatory gene mRNA in three different types of human trophoblasts and effect of transforming growth factor. J Obstet Gynaecol Res. 2008;34(2):152-161. DOI: https://doi.org/10.1111/j.1447-0756.2008.00753.x
59. Graham CH, Connelly I, MacDougall JR, Kerbel RS, Stetler-Stevenson WG, Lala PK. Resistance of malignant trophoblast cells to both the anti-proliferative and anti-invasive effects of transforming growth factor-beta. Experimental Cell Research. 1994;214(1):93-99. DOI: https://doi.org/10.1006/excr.1994.1237
60. Karmakar S, Das C. Regulation of Trophoblast Invasion by IL-1β and TGF- β1. American Journal Of Reproductive Immunology. 2002;48(4):210-219. DOI: http://dx.doi.org/10.1034/j.1600-0897.2002.01151.x
61. Lash GE, Otun HA, Innes BA, Bulmer JN, Searle RF, Robson SC. Inhibition of trophoblast cell invasion by TGFB1, 2, and 3 is associated with a decrease in active proteases. Biol Reprod. 2005;73(2):374-381. DOI: https://doi.org/10.1095/biolreprod.105.040337
62. Zhao M-r, Qiu W, Li Y-x, Zhang Z-b, Li D, Wang Y-l. Dual effect of transforming growth factor β1 on cell adhesion and invasion in human placenta trophoblast cells. Reproduction. 2006;132(2):333-341. DOI: http://dx.doi.org/10.1530/rep.1.01112
63. Shimonovitz S, Hurwitz A, Barak V, et al. Cytokine-mediated regulation of type IV collagenase expression and production in human trophoblast cells. Journal of Clinical Endocrinology & Metabolism. 1996;81(8):3091-3096. DOI: http://dx.doi.org/10.1210/jc.81.8.3091
64. Novoa Herrán SS, Castelblanco M, Sánchez -Gómez M, Umaña Pérez A. Transforming Growth Factor Beta has dual effects on MMP9 and uPA expression in HTR-8/SVneo human trophoblastic cell line. Acta Biológica Colombiana. 2019;24:26-37. http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S0120-548X2019000100026&nrm=iso
65. Irving JA, Lala PK. Functional Role of Cell Surface Integrins on Human Trophoblast Cell Migration: Regulation by TGF-[beta], IGF-II, and IGFBP-1. Experimental Cell Research. 1995;217(2):419-427. DOI: https://doi.org/10.1006/excr.1995.1105.
66. Karmakar S, Das C. Modulation of ezrin and E-cadherin expression by IL-1beta and TGF-beta1 in human trophoblasts. J Reprod Immunol. 2004;64(1-2):9-29. DOI: https://doi.org/10.1016/j.jri.2004.04.005
67. Novoa-Herrán SS, Monge M, Canals F, Sanchez-Gomez M. Transforming Growth Factor beta regulates novel proteins in a human trophoblastic cell model. Paper presented at: 13th Annual World Congress of the Human Proteome Organization2014; Madrid, Spain.
68. Sonderegger S, Husslein H, Leisser C, Knofler M. Complex expression pattern of Wnt ligands and frizzled receptors in human placenta and its trophoblast subtypes. Placenta. 2007;28 Suppl A:S97-102. DOI: https://doi.org/10.1016/j.placenta.2006.11.003
69. Pollheimer J, Loregger T, Sonderegger S, et al. Activation of the canonical wingless/T-cell factor signaling pathway promotes invasive differentiation of human trophoblast. Am J Pathol. 2006;168(4):1134-1147. DOI: https://doi.org/10.2353/ajpath.2006.050686
70. Knofler M. Critical growth factors and signalling pathways controlling human trophoblast invasion. Int J Dev Biol. 2010;54(2-3):269-280. DOI: https://doi.org/10.1387/ijdb.082769mk
71. Cuman C, Menkhorst E, Winship A, et al. Fetal-maternal communication: the role of Notch signalling in embryo implantation. Reproduction. 2014;147(3):R75-86. DOI: https://doi.org/10.1530/REP-13-0474
72. Poteser M, Hutter HP, Moshammer H, Weitensfelder L. Perfluoroctanoic acid (PFOA) enhances NOTCH-signaling in an angiogenesis model of placental trophoblast cells. Int J Hyg Environ Health. 2020;229:113566. DOI: https://doi.org/10.1016/j.ijheh.2020.113566
73. LaFoya B, Munroe JA, Mia MM, et al. Notch: A multi-functional integrating system of microenvironmental signals. Dev Biol. 2016;418(2):227-241. DOI: https://doi.org/10.1016/j.ydbio.2016.08.023
74. Nachtigall MJ, Kliman HJ, Feinberg RF, Olive DL, Engin O, Arici A. The effect of leukemia inhibitory factor (LIF) on trophoblast differentiation: a potential role in human implantation. J Clin Endocrinol Metab. 1996;81(2):801-806. DOI: https://doi.org/10.1210/jcem.81.2.8636307
75. Suman P, Gupta SK. STAT3 and ERK1/2 cross-talk in leukaemia inhibitory factor mediated trophoblastic JEG-3 cell invasion and expression of mucin 1 and Fos. Am J Reprod Immunol. 2014;72(1):65-74. DOI: https://doi.org/10.1111/aji.12248
76. Singh M, Kindelberger D, Nagymanyoki Z, et al. Matrix metalloproteinases and their inhibitors and inducer in gestational trophoblastic diseases and normal placenta. Gynecologic Oncology. 2011;122(1):178-182. DOI: https://doi.org/10.1016/j.ygyno.2011.03.025
77. Bourboulia D, Stetler-Stevenson WG. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): Positive and negative regulators in tumor cell adhesion. Seminars in cancer biology. 2010;20(3):161-168. DOI: https://doi.org/10.1016/j.semcancer.2010.05.002
78. Su CW, Lin CW, Yang WE, Yang SF. TIMP-3 as a therapeutic target for cancer. Ther Adv Med Oncol. 2019;11:1758835919864247. DOI: https://doi.org/10.1177/1758835919864247
79. Lee SY, Oh JY, Kang TH, et al. Endoplasmic reticulum stress enhances the antigen-specific T cell immune responses and therapeutic antitumor effects generated by therapeutic HPV vaccines. J Biomed Sci. 2019;26(1):41. DOI: 10.1186/s12929-019-0536-7
80. Zhang H, Hou L, Li CM, Zhang WY. The chemokine CXCL6 restricts human trophoblast cell migration and invasion by suppressing MMP-2 activity in the first trimester. Hum Reprod. 2013;28(9):2350-2362. DOI: https://doi.org/10.1093/humrep/det258
81. Coppock HA, White A, Aplin JD, Westwood M. Matrix metalloprotease-3 and -9 proteolyze insulin-like growth factor-binding protein-1. Biol Reprod. 2004;71(2):438-443. DOI: 10.1095/biolreprod.103.023101
82. Zhao Y, Lyons CE, Jr., Xiao A, et al. Urokinase directly activates matrix metalloproteinases-9: a potential role in glioblastoma invasion. Biochemical and biophysical research communications. 2008;369(4):1215-1220. DOI: https://doi.org/10.1016/j.bbrc.2008.03.038
83. Liu J, Chakraborty C, Graham CH, Barbin YP, Dixon SJ, Lala PK. Noncatalytic domain of uPA stimulates human extravillous trophoblast migration by using phospholipase C, phosphatidylinositol 3-kinase and mitogen-activated protein kinase. Experimental Cell Research. 2003;286(1):138-151. DOI: https://doi.org/10.1016/S0014-4827(03)00089-2
84. Espino Y Sosa S, Flores-Pliego A, Espejel-Nuñez A, et al. New Insights into the Role of Matrix Metalloproteinases in Preeclampsia. International journal of molecular sciences. 2017;18(7). DOI: https://doi.org/10.3390/ijms18071448
85. Burton GJ, Cindrova-Davies T, Yung Hw, Jauniaux E. Oxygen and development of the human placenta. 2020:REP-20-0153. DOI: 10.1530/rep-20-0153
86. Burton GJ, Cindrova-Davies T, Turco MY. Review: Histotrophic nutrition and the placental-endometrial dialogue during human early pregnancy. Placenta. 2020. DOI: https://doi.org/10.1016/j.placenta.2020.02.008
87. Novoa-Herran S, Umana-Perez A, Canals F, Sanchez-Gomez M. Serum depletion induces changes in protein expression in the trophoblast-derived cell line HTR-8/SVneo. Cell Mol Biol Lett. 2016;21:22. DOI: https://doi.org/10.1186/s11658-016-0018-9
88. Altieri A, Franceschi S, Ferlay J, Smith J, La Vecchia C. Epidemiology and aetiology of gestational trophoblastic diseases. Lancet Oncol. 2003;4(11):670-678. DOI: https://doi.org/10.1016/s1470-2045(03)01245-2
89. Candelier JJ. The hydatidiform mole. Cell Adh Migr. 2015;10(1-2):226-235. DOI: https://doi.org/10.1080/19336918.2015.1093275
90. Hernandez AA. Clínica, ginecología y obstetricia. Enfermedad trofoblástica. Madrid, España: Interamericana; 2006:297-301.
91. Cole LA. New discoveries on the biology and detection of human chorionic gonadotropin. Reprod Biol Endocrinol. 2009;7:8. DOI: https://doi.org/10.1186/1477-7827-7-8
92. Bermudez AJ, Córtes C, Díaz LE. Área Clínica: Estudio Bioquímico y Genético de la Enfermedad Troboblástica Gestacional Medicina. 2006;28(1):14-18. https://revistamedicina.net/ojsanm/index.php/Medicina/article/view/72-3
93. Society AC. What Is Gestational Trophoblastic Disease? , https://www.cancer.org/cancer/gestational-trophoblastic-disease/about/what-is-gtd.html
94. Braga A, Lin LH, Maesta I, et al. Gestational Trophoblastic Disease in Brazil. Rev Bras Ginecol Obstet. 2019;41(4):211-212. DOI: https://doi.org/10.1055/s-0039-1688566
95. Cortés C, Ching R, Rodríguez A, et al. La mola hidatidiforme: un indicador de la situación sociodemográfica en salud sexual y reproductiva. Inf Quinc Epidemiol Nac. 2003;12(8):193-208.
96. Lurain JR. Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole. Am J Obstet Gynecol. 2010;203(6):531-539. DOI: https://doi.org/10.1016/j.ajog.2010.06.073
97. Lustig-Yariv O, Schulze E, Komitowski D, et al. The expression of the imprinted genes H19 and IGF-2 in choriocarcinoma cell lines. Is H19 a tumor suppressor gene? Oncogene. 1997;15(2):169-177. DOI: https://doi.org/10.1038/sj.onc.1201175
98. Kim SJ, Park SE, Lee C, et al. Altered imprinting, promoter usage, and expression of insulin-like growth factor-II gene in gestational trophoblastic diseases. Gynecol Oncol. 2003;88(3):411-418. DOI: https://doi.org/10.1016/s0090-8258(02)00143-9
99. Bernal Sierra YA, Díaz Barrera L, Acosta J, et al. Estudio inmunocitoquímico y molecular de cultivo primario de tejido molar. Biomédica. 2006;26:509-516. DOI: https://doi.org/10.7705/biomedica.v26i4.316
100. Diaz LE, Chuan YC, Lewitt M, et al. IGF-II regulates metastatic properties of choriocarcinoma cells through the activation of the insulin receptor. Mol Hum Reprod. 2007;13(8):567-576. DOI: https://doi.org/10.1093/molehr/gam039
101. Pinzón M, Diaz L, Ortiz B, Umaña A, De Rodriguez S, Sanchez de Gomez M. La activación de la vía de señalización PI3K/AKT por el factor de crecimiento similar a la insulina IGF-II estimula la expresión de ARNm de MMP-9 en células de coriocarcinoma. . Revista Colombiana de Química. 2009;38(3). https://revistas.unal.edu.co/index.php/rcolquim/article/view/13490
102. Bergman D, Bergman D, Halje M, Nordin M, Engström W. Insulin-Like Growth Factor 2 in Development and Disease: A Mini-Review. Gerontology. 2013;59(3):240-249. DOI: https://doi.org/10.1159/000343995
103. Harris LK, Pantham P, Yong HEJ, et al. The role of insulin-like growth factor 2 receptor-mediated homeobox gene expression in human placental apoptosis, and its implications in idiopathic fetal growth restriction. Molecular human reproduction. 2019;25(9):572-585. DOI: https://doi.org/10.1093/molehr/gaz047
104. Kaku K, Osada H, Seki K, Sekiya S. Insulin-like growth factor 2 (IGF2) and IGF2 receptor gene variants are associated with fetal growth. Acta Paediatr. 2007;96(3):363-367. DOI: https://doi.org/10.1111/j.1651-2227.2006.00120.x
105. Harris LK, Westwood M. Biology and significance of signalling pathways activated by IGF-II. Growth Factors. 2012;30(1):1-12. DOI: https://doi.org/10.3109/08977194.2011.640325
106. Vishwamitra D, George SK, Shi P, Kaseb AO, Amin HM. Type I insulin-like growth factor receptor signaling in hematological malignancies. Oncotarget. 2017;8(1):1814-1844. DOI: https://doi.org/10.18632/oncotarget.12123
107. Livingstone C. IGF2 and cancer. Endocr Relat Cancer. 2013;20(6):R321-339. DOI: https://doi.org/10.1530/ERC-13-0231
108. Sakano K, Enjoh T, Numata F, et al. The design, expression, and characterization of human insulin-like growth factor II (IGF-II) mutants specific for either the IGF-II/cation-independent mannose. The Journal of biological chemistry. 1991;266(31):20626-20635.
109. Forbes BE, Hartfield PJ, McNeil KA, et al. Characteristics of binding of insulin-like growth factor (IGF)-I and IGF-II analogues to the type 1 IGF receptor determined by BIAcore analysis. Eur J Biochem. 2002;269(3):961-968. DOI: https://doi.org/10.1046/j.0014-2956.2001.02735.x
110. GroPep. GroPep Bioreagents IGF Analogues. Human [Leu27]IGF-II. https://gropep.com/product_families/igf-analogues/products/human-leu27-igf-ii--7
111. Charnock JC, Dilworth MR, Aplin JD, Sibley CP, Westwood M, Crocker IP. The impact of a human IGF-II analog ([Leu27]IGF-II) on fetal growth in a mouse model of fetal growth restriction. American journal of physiology Endocrinology and metabolism. 2016;310(1):E24-31. DOI: https://doi.org/10.1152/ajpendo.00379.2015
112. Sferruzzi-Perri AN, Owens JA, Standen P, Roberts CT. Maternal insulin-like growth factor-II promotes placental functional development via the type 2 IGF receptor in the guinea pig. Placenta. 2008;29(4):347-355. DOI: https://doi.org/10.1016/j.placenta.2008.01.009
113. Okamoto T, Nishimoto I. Analysis of stimulation-G protein subunit coupling by using active insulin-like growth factor II receptor peptide. Proc Natl Acad Sci U S A. 1991;88(18):8020-8023. DOI: https://doi.org/10.1073/pnas.88.18.8020
114. Higashijima T, Uzu S, Nakajima T, Ross EM. Mastoparan, a peptide toxin from wasp venom, mimics receptors by activating. The Journal of biological chemistry. 1988;263(14):6491-6494.
115. Okamoto T, Katada T, Murayama Y, Ui M, Ogata E, Nishimoto I. A simple structure encodes G protein-activating function of the IGF-II/mannose. Cell. 1990;62(4):709-717. DOI: https://doi.org/10.1016/0092-8674(90)90116-v
116. Wang KCW, Tosh DN, Zhang S, et al. IGF-2R-Galphaq signaling and cardiac hypertrophy in the low-birth-weight lamb. Am J Physiol Regul Integr Comp Physiol. 2015;308(7):R627-635. DOI: https://doi.org/10.1152/ajpregu.00346.2014
117. Wang KCW, Brooks DA, Botting KJ, Morrison JL. IGF-2R-mediated signaling results in hypertrophy of cultured cardiomyocytes from fetal sheep. Biology of reproduction. 2012;86(6):183. DOI: https://doi.org/10.1095/biolreprod.112.100388
118. Chen R-J, Wu H-C, Chang M-H, et al. Leu27IGF2 plays an opposite role to IGF1 to induce H9c2 cardiomyoblast cell apoptosis via Galphaq signaling. J Mol Endocrinol. 2009;43(6):221-230. DOI: https://doi.org/10.1677/JME-08-0121
119. Harris LK, Crocker IP, Baker PN, Aplin JD, Westwood M. IGF2 actions on trophoblast in human placenta are regulated by the insulin-like growth factor 2 receptor, which can function as both a signaling and clearance receptor. Biology of reproduction. 2011;84(3):440-446. DOI: https://doi.org/10.1095/biolreprod.110.088195
120. Pang Z-J, Xing F-Q. Expression of transforming growth factor-β and insulin-like growth factor in molar and placental tissues. Archives of Gynecology and Obstetrics. 2003;269(1):1-4. DOI: https://doi.org/10.1007/s00404-002-0379-3
121. Bolat F, Haberal N, Tunali N, Aslan E, Bal N, Tuncer I. Expression of vascular endothelial growth factor (VEGF), hypoxia inducible factor 1 alpha (HIF-1α), and transforming growth factors β1 (TGFβ1) and β3 (TGFβ3) in gestational trophoblastic disease. Pathology - Research and Practice. 2010;206(1):19-23. DOI: https://doi.org/10.1016/j.prp.2009.07.017
122. Dehaghani AS, Rad NR, Fattahi MJ, et al. Investigation of soluble HER2 and transforming growth factor Beta-1 serum levels in gestational trophoblastic disease. Pathol Oncol Res. 2009;15(1):37-40. DOI: https://doi.org/10.1007/s12253-008-9115-z
123. Xu G, Chakraborty C, Lala PK. Expression of TGF-β Signaling Genes in the Normal, Premalignant, and Malignant Human Trophoblast: Loss of Smad3 in Choriocarcinoma Cells. Biochemical and Biophysical Research Communications. 2001;287(1):47-55. DOI: http://dx.doi.org/10.1006/bbrc.2001.5533
124. Xu G, Chakraborty C, Lala PK. Restoration of TGF-β regulation of plasminogen activator inhibitor-1 in Smad3-restituted human choriocarcinoma cells. Biochemical and Biophysical Research Communications. 2002;294(5):1079-1086. DOI: https://doi.org/10.1016/S0006-291X(02)00605-8
125. Xu G, Chakraborty C, Lala PK. Reconstitution of Smad3 restores TGF-β response of tissue inhibitor of metalloprotease-1 upregulation in human choriocarcinoma cells. Biochemical and Biophysical Research Communications. 2003;300(2):383-390. DOI: http://dx.doi.org/10.1016/S0006-291X(02)02845-0
126. Lafontaine L, Chaudhry P, Lafleur MJ, Van Themsche C, Soares MJ, Asselin E. Transforming growth factor Beta regulates proliferation and invasion of rat placental cell lines. Biol Reprod. 2011;84(3):553-559. DOI: https://doi.org/10.1095/biolreprod.110.086348
127. Syed V. TGF-β Signaling in Cancer. Journal of Cellular Biochemistry. 2016;117(6):1279-1287. DOI: https://doi.org/10.1002/jcb.25496
128. Li Y, Xu Q, Zhang Z, Liu S, Shi C, Tan Y. The impact of TGF-β1 on the mRNA expression of TβR I, TβR II, Smad4 and the invasiveness of the JEG-3 placental choriocarcinoma cell line. Oncology Letters. 2012;4(6):1344-1348. DOI: https://doi.org/10.3892/ol.2012.906
129. Wolf N, Yang W, Dunk CE, et al. Regulation of the Matricellular Proteins CYR61 (CCN1) and NOV (CCN3) by Hypoxia-Inducible Factor-1α and Transforming-Growth Factor-β3 in the Human Trophoblast. Endocrinology. 2010;151(6):2835-2845. DOI: https://doi.org/10.1210/en.2009-1195
130. Papadimitriou E, Kardassis D, Moustakas A, Stournaras C. TGFbeta-induced early activation of the small GTPase RhoA is Smad2/3-independent and involves Src and the guanine nucleotide exchange factor Vav2. Cell Physiol Biochem. 2011;28(2):229-238. DOI: https://doi.org/10.1159/000331734
131. Vardouli L, Vasilaki E, Papadimitriou E, Kardassis D, Stournaras C. A novel mechanism of TGFβ-induced actin reorganization mediated by Smad proteins and Rho GTPases. The FEBS Journal. 2008;275(16):4074-4087. DOI: https://doi.org/10.1111/j.1742-4658.2008.06549.x
132. Xu Q, Tan Y, Zhang K, Li Y. Crosstalk between p38 and Smad3 through TGF-beta1 in JEG-3 choriocarcinoma cells. Int J Oncol. 2013;43(4):1187-1193. DOI: https://doi.org/10.3892/ijo.2013.2026
133. Tan Y, Xu Q, Li Y, Mao X, Zhang K. Crosstalk between the p38 and TGF-β signaling pathways through TβRI, TβRII and Smad3 expression in plancental choriocarcinoma JEG-3 cells. Oncology Letters. 2014;8(3):1307-1311. DOI: https://doi.org/10.3892/ol.2014.2255
134. Tufegdzic Vidakovic A, Rueda OM, Vervoort SJ, et al. Context-Specific Effects of TGF-beta/SMAD3 in Cancer Are Modulated by the Epigenome. Cell Rep. 2015;13(11):2480-2490. DOI: https://doi.org/10.1016/j.celrep.2015.11.040
135. Bai J, Xi Q. Crosstalk between TGF-beta signaling and epigenome. Acta Biochim Biophys Sin (Shanghai). 2018;50(3):322. DOI: https://doi.org/10.1093/abbs/gmy001
136. Cardenas H, Vieth E, Lee J, et al. TGF-beta induces global changes in DNA methylation during the epithelial-to-mesenchymal transition in ovarian cancer cells. Epigenetics. 2014;9(11):1461-1472. DOI: https://doi.org/10.4161/15592294.2014.971608
137. Singh V, Singh AP, Sharma I, et al. Epigenetic deregulations of Wnt/beta-catenin and transforming growth factor beta-Smad pathways in esophageal cancer: Outcome of DNA methylation. J Cancer Res Ther. 2019;15(1):192-203. DOI: https://doi.org/10.4103/jcrt.JCRT_634_17
138. Suriyamurthy S, Baker D, Ten Dijke P, Iyengar PV. Epigenetic Reprogramming of TGF-beta Signaling in Breast Cancer. Cancers (Basel). 2019;11(5). DOI: https://doi.org/10.3390/cancers11050726
139. Lee C, Zhang Q, Zi X, et al. TGF-beta mediated DNA methylation in prostate cancer. Transl Androl Urol. 2012;1(2):78-88. DOI: https://doi.org/10.3978/j.issn.2223-4683.2012.05.06
140. Morales E, Vilahur N, Salas LA, et al. Genome-wide DNA methylation study in human placenta identifies novel loci associated with maternal smoking during pregnancy. Int J Epidemiol. 2016;45(5):1644-1655. DOI: https://doi.org/10.1093/ije/dyw196
141. Mandal C, Halder D, Jung KH, Chai YG. Gestational Alcohol Exposure Altered DNA Methylation Status in the Developing Fetus. Int J Mol Sci. 2017;18(7). DOI: https://doi.org/10.3390/ijms18071386
142. Nogues P, Dos Santos E, Jammes H, et al. Maternal obesity influences expression and DNA methylation of the adiponectin and leptin systems in human third-trimester placenta. Clin Epigenetics. 2019;11(1):20. DOI: https://doi.org/10.1186/s13148-019-0612-6
143. Daniels TE, Sadovnikoff AI, Ridout KK, Lesseur C, Marsit CJ, Tyrka AR. Associations of maternal diet and placenta leptin methylation. Mol Cell Endocrinol. 2020;505:110739. DOI: https://doi.org/10.1016/j.mce.2020.110739
144. Workalemahu T, Ouidir M, Shrestha D, Wu J, Grantz KL, Tekola-Ayele F. Differential DNA Methylation in Placenta Associated With Maternal Blood Pressure During Pregnancy. Hypertension. 2020;75(4):1117-1124. DOI: https://doi.org/10.1161/HYPERTENSIONAHA.119.14509
145. Santos HP, Jr., Bhattacharya A, Martin EM, et al. Epigenome-wide DNA methylation in placentas from preterm infants: association with maternal socioeconomic status. Epigenetics. 2019;14(8):751-765. DOI: https://doi.org/10.1080/15592294.2019.1614743
146. Dwi Putra SE, Reichetzeder C, Hasan AA, et al. Being Born Large for Gestational Age is Associated with Increased Global Placental DNA Methylation. Sci Rep. 2020;10(1):927. DOI: https://doi.org/10.1038/s41598-020-57725-0
147. Clarkson-Townsend DA, Everson TM, Deyssenroth MA, et al. Maternal circadian disruption is associated with variation in placental DNA methylation. PLoS One. 2019;14(4):e0215745. DOI: https://doi.org/10.1371/journal.pone.0215745
148. Schuster J, Uzun A, Stablia J, Schorl C, Mori M, Padbury JF. Effect of prematurity on genome wide methylation in the placenta. BMC Med Genet. 2019;20(1):116. DOI: https://doi.org/10.1186/s12881-019-0835-6
149. Petropoulos S, Guillemin C, Ergaz Z, et al. Gestational Diabetes Alters Offspring DNA Methylation Profiles in Human and Rat: Identification of Key Pathways Involved in Endocrine System Disorders, Insulin Signaling, Diabetes Signaling, and ILK Signaling. Endocrinology. 2015;156(6):2222-2238. DOI: https://doi.org/10.1210/en.2014-1643
150. Hillman SL, Finer S, Smart MC, et al. Novel DNA methylation profiles associated with key gene regulation and transcription pathways in blood and placenta of growth-restricted neonates. Epigenetics. 2015;10(1):50-61. DOI: https://doi.org/10.4161/15592294.2014.989741
151. Finer S, Mathews C, Lowe R, et al. Maternal gestational diabetes is associated with genome-wide DNA methylation variation in placenta and cord blood of exposed offspring. Hum Mol Genet. 2015;24(11):3021-3029. DOI: https://doi.org/10.1093/hmg/ddv013
152. Chu T, Bunce K, Shaw P, et al. Comprehensive analysis of preeclampsia-associated DNA methylation in the placenta. PLoS One. 2014;9(9):e107318. DOI: https://doi.org/10.1371/journal.pone.0107318
153. Anton L, Brown AG, Bartolomei MS, Elovitz MA. Differential methylation of genes associated with cell adhesion in preeclamptic placentas. PLoS One. 2014;9(6):e100148. DOI: https://doi.org/10.1371/journal.pone.0100148
154. Jia RZ, Zhang X, Hu P, et al. Screening for differential methylation status in human placenta in preeclampsia using a CpG island plus promoter microarray. Int J Mol Med. 2012;30(1):133-141. DOI: https://doi.org/10.3892/ijmm.2012.983
155. Ruchat SM, Houde AA, Voisin G, et al. Gestational diabetes mellitus epigenetically affects genes predominantly involved in metabolic diseases. Epigenetics. 2013;8(9):935-943. DOI: https://doi.org/10.4161/epi.25578
156. Lambertini L, Lee TL, Chan WY, et al. Differential methylation of imprinted genes in growth-restricted placentas. Reprod Sci. 2011;18(11):1111-1117. DOI: https://doi.org/10.1177/1933719111404611
157. Banister CE, Koestler DC, Maccani MA, Padbury JF, Houseman EA, Marsit CJ. Infant growth restriction is associated with distinct patterns of DNA methylation in human placentas. Epigenetics. 2011;6(7):920-927. DOI: https://dx.doi.org/10.4161%2Fepi.6.7.16079
158. Blair JD, Yuen RK, Lim BK, McFadden DE, von Dadelszen P, Robinson WP. Widespread DNA hypomethylation at gene enhancer regions in placentas associated with early-onset pre-eclampsia. Mol Hum Reprod. 2013;19(10):697-708. DOI: https://doi.org/10.1093/molehr/gat044
159. El Hajj N, Pliushch G, Schneider E, et al. Metabolic programming of MEST DNA methylation by intrauterine exposure to gestational diabetes mellitus. Diabetes. 2013;62(4):1320-1328. DOI: https://doi.org/10.2337/db12-0289
160. Howe CG, Cox B, Fore R, et al. Maternal Gestational Diabetes Mellitus and Newborn DNA Methylation: Findings From the Pregnancy and Childhood Epigenetics Consortium. Diabetes Care. 2020;43(1):98-105. DOI: https://doi.org/10.2337/dc19-0524
161. Rong C, Cui X, Chen J, Qian Y, Jia R, Hu Y. DNA methylation profiles in placenta and its association with gestational diabetes mellitus. Exp Clin Endocrinol Diabetes. 2015;123(5):282-288. DOI: https://doi.org/10.1055/s-0034-1398666
162. Weng X, Liu F, Zhang H, et al. Genome-wide DNA methylation profiling in infants born to gestational diabetes mellitus. Diabetes Res Clin Pract. 2018;142:10-18. DOI: https://doi.org/10.1016/j.diabres.2018.03.016
163. Elliott HR, Sharp GC, Relton CL, Lawlor DA. Epigenetics and gestational diabetes: a review of epigenetic epidemiology studies and their use to explore epigenetic mediation and improve prediction. Diabetologia. 2019;62(12):2171-2178. DOI: https://doi.org/10.1007/s00125-019-05011-8
164. Hivert MF, Cardenas A, Allard C, et al. Interplay of Placental DNA Methylation and Maternal Insulin Sensitivity in Pregnancy. Diabetes. 2020;69(3):484-492. DOI: https://doi.org/10.2337/db19-0798
165. Cardenas A, Gagne-Ouellet V, Allard C, et al. Placental DNA Methylation Adaptation to Maternal Glycemic Response in Pregnancy. Diabetes. 2018;67(8):1673-1683. DOI: https://doi.org/10.2337/db18-0123
166. Mousa AA, Archer KJ, Cappello R, et al. DNA methylation is altered in maternal blood vessels of women with preeclampsia. Reprod Sci. 2012;19(12):1332-1342. DOI: https://doi.org/10.1177/1933719112450336
167. Yeung KR, Chiu CL, Pidsley R, Makris A, Hennessy A, Lind JM. DNA methylation profiles in preeclampsia and healthy control placentas. Am J Physiol Heart Circ Physiol. 2016;310(10):H1295-1303. DOI: https://doi.org/10.1152/ajpheart.00958.2015
168. Demond H, Anvar Z, Jahromi BN, et al. A KHDC3L mutation resulting in recurrent hydatidiform mole causes genome-wide DNA methylation loss in oocytes and persistent imprinting defects post-fertilisation. Genome Med. 2019;11(1):84. DOI: https://doi.org/10.1186/s13073-019-0694-y
169. Xiao X, Zhao Y, Jin R, et al. Fetal growth restriction and methylation of growth-related genes in the placenta. Epigenomics. 2016;8(1):33-42. DOI: https://doi.org/10.2217/epi.15.101
170. Thompson RF, Fazzari MJ, Niu H, Barzilai N, Simmons RA, Greally JM. Experimental intrauterine growth restriction induces alterations in DNA methylation and gene expression in pancreatic islets of rats. J Biol Chem. 2010;285(20):15111-15118. DOI: https://doi.org/10.1074/jbc.M109.095133
171. Hu Y, Hu L, Gong D, et al. Genome-wide DNA methylation analysis in jejunum of Sus scrofa with intrauterine growth restriction. Mol Genet Genomics. 2018;293(4):807-818. DOI: https://doi.org/10.1007/s00438-018-1422-9
172. Einstein F, Thompson RF, Bhagat TD, et al. Cytosine methylation dysregulation in neonates following intrauterine growth restriction. PLoS One. 2010;5(1):e8887. DOI: https://doi.org/10.1371/journal.pone.0008887
173. Roifman M, Choufani S, Turinsky AL, et al. Genome-wide placental DNA methylation analysis of severely growth-discordant monochorionic twins reveals novel epigenetic targets for intrauterine growth restriction. Clin Epigenetics. 2016;8:70. DOI: https://doi.org/10.1186/s13148-016-0238-x
174. Chabrun F, Huetz N, Dieu X, et al. Data-Mining Approach on Transcriptomics and Methylomics Placental Analysis Highlights Genes in Fetal Growth Restriction. Front Genet. 2019;10:1292. DOI: https://doi.org/10.3389/fgene.2019.01292
175. Smith ZD, Shi J, Gu H, et al. Epigenetic restriction of extraembryonic lineages mirrors the somatic transition to cancer. Nature. 2017;549(7673):543-547. DOI: https://doi.org/10.1038/nature23891
176. Nordor AV, Nehar-Belaid D, Richon S, et al. The early pregnancy placenta foreshadows DNA methylation alterations of solid tumors. Epigenetics. 2017;12(9):793-803. DOI: https://doi.org/10.1080/15592294.2017.1342912
2. Vlahos A, Mansell T, Saffery R, Novakovic B. Human placental methylome in the interplay of adverse placental health, environmental exposure, and pregnancy outcome. PLoS Genet. 2019;15(8):e1008236. DOI: https://doi.org/10.1371/journal.pgen.1008236
3. Lindhard A, Bentin-Ley U, Ravn V, et al. Biochemical evaluation of endometrial function at the time of implantation. 2002;78(2):221-233. DOI: https://doi.org//10.1016/S0015-0282(02)03240-5
4. Armant DR. Blastocysts don't go it alone. Extrinsic signals fine-tune the intrinsic developmental program of trophoblast cells. Developmental biology. 2005;280(2):260-280. DOI: https://doi.org/10.1016/j.ydbio.2005.02.009
5. Carter AM, Enders AC, Pijnenborg R. The role of invasive trophoblast in implantation and placentation of primates. Philosophical transactions of the Royal Society of London Series B, Biological sciences. 2015;370(1663):20140070. DOI: https://doi.org/10.1098/rstb.2014.0070
6. Cross JC, Werb Z, Fisher SJ. Implantation and the placenta: key pieces of the development puzzle. Science. 1994;266(5190):1508-1518. DOI: https://doi.org/10.1126/science.7985020
7. Jansson T, Powell TL. IFPA 2005 Award in Placentology Lecture. Human placental transport in altered fetal growth: does the placenta function as a nutrient sensor? -- a review. Placenta. 2006;27 Suppl A:S91-97. DOI: 10.1016/j.placenta.2005.11.010
8. Ferretti C, Bruni L, Dangles-Marie V, Pecking AP, Bellet D. Molecular circuits shared by placental and cancer cells, and their implications in the proliferative, invasive and migratory capacities of trophoblasts. Hum Reprod Update. 2007;13(2):121-141. DOI: https://doi.org/10.1093/humupd/dml048
9. Poste G, Fidler IJ. The pathogenesis of cancer metastasis. Nature. 1980;283(5743):139-146. DOI: https://doi.org/10.1038/283139a0
10. Weiss G, Sundl M, Glasner A, Huppertz B, Moser G. The trophoblast plug during early pregnancy: a deeper insight. Histochem Cell Biol. 2016;146(6):749-756. DOI: https://doi.org/10.1007/s00418-016-1474-z
11. Moser G, Windsperger K, Pollheimer J, de Sousa Lopes SC, Huppertz B. Human trophoblast invasion: new and unexpected routes and functions. Histochem Cell Biol. 2018;150(4):361-370. DOI: https://doi.org/10.1007/s00418-018-1699-0
12. Moser G, Gauster M, Orendi K, Glasner A, Theuerkauf R, Huppertz B. Endoglandular trophoblast, an alternative route of trophoblast invasion? Analysis with novel confrontation co-culture models. Hum Reprod. 2010;25(5):1127-1136. DOI: https://doi.org/10.1093/humrep/deq035
13. Huppertz B, Weiss G, Moser G. Trophoblast invasion and oxygenation of the placenta: measurements versus presumptions. J Reprod Immunol. 2014;101-102:74-79. DOI: https://doi.org/10.1016/j.jri.2013.04.003
14. Chakraborty C, Gleeson LM, McKinnon T, Lala PK. Regulation of human trophoblast migration and invasiveness. Can J Physiol Pharmacol. 2002;80(2):116-124. DOI: https://doi.org/10.1139/y02-016
15. LeRoith D, Roberts CT, Jr. The insulin-like growth factor system and cancer. Cancer Lett. 2003;195(2):127-137. DOI: https://doi.org/10.1016/s0304-3835(03)00159-9
16. LeRoith D, Werner H, Neuenschwander S, Kalebic T, Helman LJ. The role of the insulin-like growth factor-I receptor in cancer. Ann N Y Acad Sci. 1995;766:402-408. DOI: https://doi.org/10.1111/j.1749-6632.1995.tb26689.x
17. Samani AA, Yakar S, LeRoith D, Brodt P. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr Rev. 2007;28(1):20-47. DOI: https://doi.org/10.1210/er.2006-0001
18. Belfiore A, Frasca F, Pandini G, Sciacca L, Vigneri R. Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease. Endocr Rev. 2009;30(6):586-623. DOI: https://doi.org/10.1210/er.2008-0047
19. Pandini G, Frasca F, Mineo R, Sciacca L, Vigneri R, Belfiore A. Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved. J Biol Chem. 2002;277(42):39684-39695. DOI: https://doi.org/10.1074/jbc.M202766200
20. El-Shewy HM, Luttrell LM. Insulin-like growth factor-2/mannose-6 phosphate receptors. Vitamins and hormones. 2009;80:667-697. DOI: https://doi.org/10.1016/S0083-6729(08)00624-9
21. Han VK, Bassett N, Walton J, Challis JR. The expression of insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) genes in the human placenta and membranes: evidence for IGF-IGFBP interactions at the feto-maternal interface. J Clin Endocrinol Metab. 1996;81(7):2680-2693. DOI: https://doi.org/10.1210/jcem.81.7.8675597
22. Holmes R, Porter H, Newcomb P, Holly JM, Soothill P. An immunohistochemical study of type I insulin-like growth factor receptors in the placentae of pregnancies with appropriately grown or growth restricted fetuses. Placenta. 1999;20(4):325-330. DOI: https://doi.org/10.1053/plac.1998.0387
23. Forbes K, Westwood M, Baker PN, Aplin JD. Insulin-like growth factor I and II regulate the life cycle of trophoblast in the developing human placenta. American journal of physiology Cell physiology. 2008;294(6):C1313-1322. DOI: https://doi.org/10.1152/ajpcell.00035.2008
24. Kooijman R. Regulation of apoptosis by insulin-like growth factor (IGF)-I. Cytokine Growth Factor Rev. 2006;17(4):305-323. DOI: https://doi.org/10.1016/j.cytogfr.2006.02.002
25. Forbes K, Shah VK, Siddals K, Gibson JM, Aplin JD, Westwood M. Statins inhibit insulin-like growth factor action in first trimester placenta by altering insulin-like growth factor 1 receptor glycosylation. Mol Hum Reprod. 2015;21(1):105-114. DOI: https://doi.org/10.1093/molehr/gau093
26. Constancia M, Hemberger M, Hughes J, et al. Placental-specific IGF-II is a major modulator of placental and fetal growth. Nature. 2002;417(6892):945-948. DOI: https://doi.org/10.1038/nature00819
27. Buckberry S, Bianco-Miotto T, Hiendleder S, Roberts CT. Quantitative allele-specific expression and DNA methylation analysis of H19, IGF2 and IGF2R in the human placenta across gestation reveals H19 imprinting plasticity. PLoS One. 2012;7(12):e51210. DOI: https://doi.org/10.1371/journal.pone.0051210
28. Fang J, Furesz TC, Lurent RS, Smith CH, Fant ME. Spatial polarization of insulin-like growth factor receptors on the human syncytiotrophoblast. Pediatric research. 1997;41(2):258-265. DOI: https://doi.org/10.1203/00006450-199702000-00017
29. El-Shewy HM, Johnson KR, Lee M-H, Jaffa AA, Obeid LM, Luttrell LM. Insulin-like growth factors mediate heterotrimeric G protein-dependent ERK1/2 activation by transactivating sphingosine 1-phosphate receptors. The Journal of biological chemistry. 2006;281(42):31399-31407. DOI: https://doi.org/10.1074/jbc.M605339200
30. McKinnon T, Chakraborty C, Gleeson LM, Chidiac P, Lala PK. Stimulation of human extravillous trophoblast migration by IGF-II is mediated by IGF type 2 receptor involving inhibitory G protein(s) and phosphorylation of MAPK. The Journal of clinical endocrinology and metabolism. 2001;86(8):3665-3674. DOI: https://doi.org/10.1210/jcem.86.8.7711
31. Brown J, Delaine C, Zaccheo OJ, et al. Structure and functional analysis of the IGF-II/IGF2R interaction. EMBO J. 2008;27(1):265-276. DOI: https://doi.org/10.1038/sj.emboj.7601938
32. Speroff L, Fritz Marc A. The Endocrinology of Pregnancy. Clinical Gynecologic Endocrinology and Fertility. Seventh Ed. ed. Philadelphia, USA: Lippincott Williams & Wilkins; 2005:287.
33. Baumann MU, Schneider H, Malek A, et al. Regulation of human trophoblast GLUT1 glucose transporter by insulin-like growth factor I (IGF-I). PLoS One. 2014;9(8):e106037. DOI: https://doi.org/10.1371/journal.pone.0106037
34. Bajoria R, Sooranna SR, Ward S, Hancock M. Placenta as a link between amino acids, insulin-IGF axis, and low birth weight: evidence from twin studies. J Clin Endocrinol Metab. 2002;87(1):308-315. DOI: https://doi.org/10.1210/jcem.87.1.8184
35. Magnusson-Olsson AL, Hamark B, Ericsson A, Wennergren M, Jansson T, Powell TL. Gestational and hormonal regulation of human placental lipoprotein lipase. J Lipid Res. 2006;47(11):2551-2561. DOI: https://doi.org/10.1194/jlr.M600098-JLR200
36. Baxter RC. Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities. Am J Physiol Endocrinol Metab. 2000;278(6):E967-976. DOI: https://doi.org/10.1152/ajpendo.2000.278.6.E967
37. Hamilton GS, Lysiak JJ, Han VK, Lala PK. Autocrine-paracrine regulation of human trophoblast invasiveness by insulin-like growth factor (IGF)-II and IGF-binding protein (IGFBP)-1. Experimental cell research. 1998;244(1):147-156. DOI: https://doi.org/10.1006/excr.1998.4195
38. Asvold BO, Eskild A, Jenum PA, Vatten LJ. Maternal concentrations of insulin-like growth factor I and insulin-like growth factor binding protein 1 during pregnancy and birth weight of offspring. Am J Epidemiol. 2011;174(2):129-135. DOI: https://doi.org/10.1093/aje/kwr067
39. Sifakis S, Akolekar R, Kappou D, Mantas N, Nicolaides KH. Maternal serum insulin-like growth factor-I at 11-13 weeks in preeclampsia. Prenat Diagn. 2010;30(11):1026-1031. DOI: https://doi.org/10.1002/pd.2555
40. Irving JA, Lala PK. Functional role of cell surface integrins on human trophoblast cell migration: regulation by TGF-beta, IGF-II, and IGFBP-1. Exp Cell Res. 1995;217(2):419-427. DOI: https://doi.org/10.1006/excr.1995.1105
41. Chakraborty C, Barbin YP, Chakrabarti S, Chidiac P, Dixon SJ, Lala PK. Endothelin-1 promotes migration and induces elevation of [Ca2+]i and phosphorylation of MAP kinase of a human extravillous trophoblast cell line. Mol Cell Endocrinol. 2003;201(1-2):63-73. DOI: https://doi.org/10.1016/s0303-7207(02)00431-8
42. Novoa Herrán S, Sanchez-Gomez M. El IGF-II estimula la actividad de MMP-9 y MMP-2 en un modelo de trofoblasto humano. Acta Biológica Colombiana. 2011;16:121-132. https://revistas.unal.edu.co/index.php/actabiol/article/view/15816/28142
43. Pardali K, Moustakas A. Actions of TGF-beta as tumor suppressor and pro-metastatic factor in human cancer. Biochim Biophys Acta. 2007;1775(1):21-62. DOI: https://doi.org/10.1016/j.bbcan.2006.06.004
44. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 2003;113(6):685-700. DOI: https://doi.org/10.1016/s0092-8674(03)00432-x
45. Schmierer B, Hill CS. TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility. Nat Rev Mol Cell Biol. 2007;8(12):970-982. DOI: https://doi.org/10.1038/nrm2297
46. Vuckovic M, Genbacev O, Kumar S. Immunohistochemical localisation of transforming growth factor-beta in first and third trimester human placenta. Pathobiology. 1992;60(3):149-151. DOI: https://doi.org/10.1159/000163714
47. Xuan YH, Choi YL, Shin YK, et al. Expression of TGF-beta signaling proteins in normal placenta and gestational trophoblastic disease. Histol Histopathol. 2007;22(3):227-234. DOI: https://doi.org/10.14670/HH-22.227
48. Karmakar S, Das C. Regulation of trophoblast invasion by IL-1beta and TGF-beta1. Am J Reprod Immunol. 2002;48(4):210-219. DOI: https://doi.org/10.1034/j.1600-0897.2002.01151.x
49. Graham CH, Lala PK. Mechanism of control of trophoblast invasion in situ. J Cell Physiol. 1991;148(2):228-234. DOI: https://doi.org/10.1002/jcp.1041480207
50. Graham CH, Lysiak JJ, McCrae KR, Lala PK. Localization of transforming growth factor-beta at the human fetal-maternal interface: role in trophoblast growth and differentiation. Biol Reprod. 1992;46(4):561-572. DOI: https://doi.org/10.1095/biolreprod46.4.561
51. Hernandez-Valencia M, Zarate A, Ochoa R, Fonseca ME, Amato D, De Jesus Ortiz M. Insulin-like growth factor I, epidermal growth factor and transforming growth factor beta expression and their association with intrauterine fetal growth retardation, such as development during human pregnancy. Diabetes, Obesity and Metabolism. 2001;3(6):457-462. DOI: https://doi.org/10.1046/j.1463-1326.2001.00168.x
52. Singh M, Orazulike NC, Ashmore J, Konje JC. Changes in maternal serum transforming growth factor beta-1 during pregnancy: a cross-sectional study. Biomed Res Int. 2013;2013:318464. DOI: https://doi.org/10.1155/2013/318464
53. Graham CH, Lysiak JJ, McCrae KR, Lala PK. Localization of Transforming Growth Factor-β at the Human Fetal-Maternal Interface: Role in Trophoblast Growth and Differentiation1. Biology of Reproduction. 1992;46(4):561-572. DOI: https://doi.org/10.1095/biolreprod46.4.561
54. Morrish DW, Bhardwaj D, Paras MT. Transforming growth factor beta 1 inhibits placental differentiation and human chorionic gonadotropin and human placental lactogen secretion. Endocrinology. 1991;129(1):22-26. DOI: https://doi.org/10.1210/endo-129-1-22
55. Song Y, Keelan J, France JT. Activin-A stimulates, while transforming growth factor β1 inhibits,chorionic gonadotrophin production and aromatase activity in cultured human placental trophoblasts. Placenta. 1996;17(8):603-610. DOI: https://doi.org/10.1016/S0143-4004(96)80078-6
56. Luo S, Yu H, Wu D, Peng C. Transforming growth factor-beta1 inhibits steroidogenesis in human trophoblast cells. Mol Hum Reprod. 2002;8(4):318-325. DOI: https://doi.org/10.1093/molehr/8.4.318
57. Meisser A, Chardonnens D, Campana A, Bischof P. Effects of tumour necrosis factor-α, interleukin-1 α, macrophage colony stimulating factor and transforming growth factor β on trophoblastic matrix metalloproteinases. Molecular Human Reproduction. 1999;5(3):252-260. DOI: http://dx.doi.org/10.1093/molehr/5.3.252
58. Richard CA, Jones JM, DeLoia JA. Comparison of cell cycle regulatory gene mRNA in three different types of human trophoblasts and effect of transforming growth factor. J Obstet Gynaecol Res. 2008;34(2):152-161. DOI: https://doi.org/10.1111/j.1447-0756.2008.00753.x
59. Graham CH, Connelly I, MacDougall JR, Kerbel RS, Stetler-Stevenson WG, Lala PK. Resistance of malignant trophoblast cells to both the anti-proliferative and anti-invasive effects of transforming growth factor-beta. Experimental Cell Research. 1994;214(1):93-99. DOI: https://doi.org/10.1006/excr.1994.1237
60. Karmakar S, Das C. Regulation of Trophoblast Invasion by IL-1β and TGF- β1. American Journal Of Reproductive Immunology. 2002;48(4):210-219. DOI: http://dx.doi.org/10.1034/j.1600-0897.2002.01151.x
61. Lash GE, Otun HA, Innes BA, Bulmer JN, Searle RF, Robson SC. Inhibition of trophoblast cell invasion by TGFB1, 2, and 3 is associated with a decrease in active proteases. Biol Reprod. 2005;73(2):374-381. DOI: https://doi.org/10.1095/biolreprod.105.040337
62. Zhao M-r, Qiu W, Li Y-x, Zhang Z-b, Li D, Wang Y-l. Dual effect of transforming growth factor β1 on cell adhesion and invasion in human placenta trophoblast cells. Reproduction. 2006;132(2):333-341. DOI: http://dx.doi.org/10.1530/rep.1.01112
63. Shimonovitz S, Hurwitz A, Barak V, et al. Cytokine-mediated regulation of type IV collagenase expression and production in human trophoblast cells. Journal of Clinical Endocrinology & Metabolism. 1996;81(8):3091-3096. DOI: http://dx.doi.org/10.1210/jc.81.8.3091
64. Novoa Herrán SS, Castelblanco M, Sánchez -Gómez M, Umaña Pérez A. Transforming Growth Factor Beta has dual effects on MMP9 and uPA expression in HTR-8/SVneo human trophoblastic cell line. Acta Biológica Colombiana. 2019;24:26-37. http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S0120-548X2019000100026&nrm=iso
65. Irving JA, Lala PK. Functional Role of Cell Surface Integrins on Human Trophoblast Cell Migration: Regulation by TGF-[beta], IGF-II, and IGFBP-1. Experimental Cell Research. 1995;217(2):419-427. DOI: https://doi.org/10.1006/excr.1995.1105.
66. Karmakar S, Das C. Modulation of ezrin and E-cadherin expression by IL-1beta and TGF-beta1 in human trophoblasts. J Reprod Immunol. 2004;64(1-2):9-29. DOI: https://doi.org/10.1016/j.jri.2004.04.005
67. Novoa-Herrán SS, Monge M, Canals F, Sanchez-Gomez M. Transforming Growth Factor beta regulates novel proteins in a human trophoblastic cell model. Paper presented at: 13th Annual World Congress of the Human Proteome Organization2014; Madrid, Spain.
68. Sonderegger S, Husslein H, Leisser C, Knofler M. Complex expression pattern of Wnt ligands and frizzled receptors in human placenta and its trophoblast subtypes. Placenta. 2007;28 Suppl A:S97-102. DOI: https://doi.org/10.1016/j.placenta.2006.11.003
69. Pollheimer J, Loregger T, Sonderegger S, et al. Activation of the canonical wingless/T-cell factor signaling pathway promotes invasive differentiation of human trophoblast. Am J Pathol. 2006;168(4):1134-1147. DOI: https://doi.org/10.2353/ajpath.2006.050686
70. Knofler M. Critical growth factors and signalling pathways controlling human trophoblast invasion. Int J Dev Biol. 2010;54(2-3):269-280. DOI: https://doi.org/10.1387/ijdb.082769mk
71. Cuman C, Menkhorst E, Winship A, et al. Fetal-maternal communication: the role of Notch signalling in embryo implantation. Reproduction. 2014;147(3):R75-86. DOI: https://doi.org/10.1530/REP-13-0474
72. Poteser M, Hutter HP, Moshammer H, Weitensfelder L. Perfluoroctanoic acid (PFOA) enhances NOTCH-signaling in an angiogenesis model of placental trophoblast cells. Int J Hyg Environ Health. 2020;229:113566. DOI: https://doi.org/10.1016/j.ijheh.2020.113566
73. LaFoya B, Munroe JA, Mia MM, et al. Notch: A multi-functional integrating system of microenvironmental signals. Dev Biol. 2016;418(2):227-241. DOI: https://doi.org/10.1016/j.ydbio.2016.08.023
74. Nachtigall MJ, Kliman HJ, Feinberg RF, Olive DL, Engin O, Arici A. The effect of leukemia inhibitory factor (LIF) on trophoblast differentiation: a potential role in human implantation. J Clin Endocrinol Metab. 1996;81(2):801-806. DOI: https://doi.org/10.1210/jcem.81.2.8636307
75. Suman P, Gupta SK. STAT3 and ERK1/2 cross-talk in leukaemia inhibitory factor mediated trophoblastic JEG-3 cell invasion and expression of mucin 1 and Fos. Am J Reprod Immunol. 2014;72(1):65-74. DOI: https://doi.org/10.1111/aji.12248
76. Singh M, Kindelberger D, Nagymanyoki Z, et al. Matrix metalloproteinases and their inhibitors and inducer in gestational trophoblastic diseases and normal placenta. Gynecologic Oncology. 2011;122(1):178-182. DOI: https://doi.org/10.1016/j.ygyno.2011.03.025
77. Bourboulia D, Stetler-Stevenson WG. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): Positive and negative regulators in tumor cell adhesion. Seminars in cancer biology. 2010;20(3):161-168. DOI: https://doi.org/10.1016/j.semcancer.2010.05.002
78. Su CW, Lin CW, Yang WE, Yang SF. TIMP-3 as a therapeutic target for cancer. Ther Adv Med Oncol. 2019;11:1758835919864247. DOI: https://doi.org/10.1177/1758835919864247
79. Lee SY, Oh JY, Kang TH, et al. Endoplasmic reticulum stress enhances the antigen-specific T cell immune responses and therapeutic antitumor effects generated by therapeutic HPV vaccines. J Biomed Sci. 2019;26(1):41. DOI: 10.1186/s12929-019-0536-7
80. Zhang H, Hou L, Li CM, Zhang WY. The chemokine CXCL6 restricts human trophoblast cell migration and invasion by suppressing MMP-2 activity in the first trimester. Hum Reprod. 2013;28(9):2350-2362. DOI: https://doi.org/10.1093/humrep/det258
81. Coppock HA, White A, Aplin JD, Westwood M. Matrix metalloprotease-3 and -9 proteolyze insulin-like growth factor-binding protein-1. Biol Reprod. 2004;71(2):438-443. DOI: 10.1095/biolreprod.103.023101
82. Zhao Y, Lyons CE, Jr., Xiao A, et al. Urokinase directly activates matrix metalloproteinases-9: a potential role in glioblastoma invasion. Biochemical and biophysical research communications. 2008;369(4):1215-1220. DOI: https://doi.org/10.1016/j.bbrc.2008.03.038
83. Liu J, Chakraborty C, Graham CH, Barbin YP, Dixon SJ, Lala PK. Noncatalytic domain of uPA stimulates human extravillous trophoblast migration by using phospholipase C, phosphatidylinositol 3-kinase and mitogen-activated protein kinase. Experimental Cell Research. 2003;286(1):138-151. DOI: https://doi.org/10.1016/S0014-4827(03)00089-2
84. Espino Y Sosa S, Flores-Pliego A, Espejel-Nuñez A, et al. New Insights into the Role of Matrix Metalloproteinases in Preeclampsia. International journal of molecular sciences. 2017;18(7). DOI: https://doi.org/10.3390/ijms18071448
85. Burton GJ, Cindrova-Davies T, Yung Hw, Jauniaux E. Oxygen and development of the human placenta. 2020:REP-20-0153. DOI: 10.1530/rep-20-0153
86. Burton GJ, Cindrova-Davies T, Turco MY. Review: Histotrophic nutrition and the placental-endometrial dialogue during human early pregnancy. Placenta. 2020. DOI: https://doi.org/10.1016/j.placenta.2020.02.008
87. Novoa-Herran S, Umana-Perez A, Canals F, Sanchez-Gomez M. Serum depletion induces changes in protein expression in the trophoblast-derived cell line HTR-8/SVneo. Cell Mol Biol Lett. 2016;21:22. DOI: https://doi.org/10.1186/s11658-016-0018-9
88. Altieri A, Franceschi S, Ferlay J, Smith J, La Vecchia C. Epidemiology and aetiology of gestational trophoblastic diseases. Lancet Oncol. 2003;4(11):670-678. DOI: https://doi.org/10.1016/s1470-2045(03)01245-2
89. Candelier JJ. The hydatidiform mole. Cell Adh Migr. 2015;10(1-2):226-235. DOI: https://doi.org/10.1080/19336918.2015.1093275
90. Hernandez AA. Clínica, ginecología y obstetricia. Enfermedad trofoblástica. Madrid, España: Interamericana; 2006:297-301.
91. Cole LA. New discoveries on the biology and detection of human chorionic gonadotropin. Reprod Biol Endocrinol. 2009;7:8. DOI: https://doi.org/10.1186/1477-7827-7-8
92. Bermudez AJ, Córtes C, Díaz LE. Área Clínica: Estudio Bioquímico y Genético de la Enfermedad Troboblástica Gestacional Medicina. 2006;28(1):14-18. https://revistamedicina.net/ojsanm/index.php/Medicina/article/view/72-3
93. Society AC. What Is Gestational Trophoblastic Disease? , https://www.cancer.org/cancer/gestational-trophoblastic-disease/about/what-is-gtd.html
94. Braga A, Lin LH, Maesta I, et al. Gestational Trophoblastic Disease in Brazil. Rev Bras Ginecol Obstet. 2019;41(4):211-212. DOI: https://doi.org/10.1055/s-0039-1688566
95. Cortés C, Ching R, Rodríguez A, et al. La mola hidatidiforme: un indicador de la situación sociodemográfica en salud sexual y reproductiva. Inf Quinc Epidemiol Nac. 2003;12(8):193-208.
96. Lurain JR. Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole. Am J Obstet Gynecol. 2010;203(6):531-539. DOI: https://doi.org/10.1016/j.ajog.2010.06.073
97. Lustig-Yariv O, Schulze E, Komitowski D, et al. The expression of the imprinted genes H19 and IGF-2 in choriocarcinoma cell lines. Is H19 a tumor suppressor gene? Oncogene. 1997;15(2):169-177. DOI: https://doi.org/10.1038/sj.onc.1201175
98. Kim SJ, Park SE, Lee C, et al. Altered imprinting, promoter usage, and expression of insulin-like growth factor-II gene in gestational trophoblastic diseases. Gynecol Oncol. 2003;88(3):411-418. DOI: https://doi.org/10.1016/s0090-8258(02)00143-9
99. Bernal Sierra YA, Díaz Barrera L, Acosta J, et al. Estudio inmunocitoquímico y molecular de cultivo primario de tejido molar. Biomédica. 2006;26:509-516. DOI: https://doi.org/10.7705/biomedica.v26i4.316
100. Diaz LE, Chuan YC, Lewitt M, et al. IGF-II regulates metastatic properties of choriocarcinoma cells through the activation of the insulin receptor. Mol Hum Reprod. 2007;13(8):567-576. DOI: https://doi.org/10.1093/molehr/gam039
101. Pinzón M, Diaz L, Ortiz B, Umaña A, De Rodriguez S, Sanchez de Gomez M. La activación de la vía de señalización PI3K/AKT por el factor de crecimiento similar a la insulina IGF-II estimula la expresión de ARNm de MMP-9 en células de coriocarcinoma. . Revista Colombiana de Química. 2009;38(3). https://revistas.unal.edu.co/index.php/rcolquim/article/view/13490
102. Bergman D, Bergman D, Halje M, Nordin M, Engström W. Insulin-Like Growth Factor 2 in Development and Disease: A Mini-Review. Gerontology. 2013;59(3):240-249. DOI: https://doi.org/10.1159/000343995
103. Harris LK, Pantham P, Yong HEJ, et al. The role of insulin-like growth factor 2 receptor-mediated homeobox gene expression in human placental apoptosis, and its implications in idiopathic fetal growth restriction. Molecular human reproduction. 2019;25(9):572-585. DOI: https://doi.org/10.1093/molehr/gaz047
104. Kaku K, Osada H, Seki K, Sekiya S. Insulin-like growth factor 2 (IGF2) and IGF2 receptor gene variants are associated with fetal growth. Acta Paediatr. 2007;96(3):363-367. DOI: https://doi.org/10.1111/j.1651-2227.2006.00120.x
105. Harris LK, Westwood M. Biology and significance of signalling pathways activated by IGF-II. Growth Factors. 2012;30(1):1-12. DOI: https://doi.org/10.3109/08977194.2011.640325
106. Vishwamitra D, George SK, Shi P, Kaseb AO, Amin HM. Type I insulin-like growth factor receptor signaling in hematological malignancies. Oncotarget. 2017;8(1):1814-1844. DOI: https://doi.org/10.18632/oncotarget.12123
107. Livingstone C. IGF2 and cancer. Endocr Relat Cancer. 2013;20(6):R321-339. DOI: https://doi.org/10.1530/ERC-13-0231
108. Sakano K, Enjoh T, Numata F, et al. The design, expression, and characterization of human insulin-like growth factor II (IGF-II) mutants specific for either the IGF-II/cation-independent mannose. The Journal of biological chemistry. 1991;266(31):20626-20635.
109. Forbes BE, Hartfield PJ, McNeil KA, et al. Characteristics of binding of insulin-like growth factor (IGF)-I and IGF-II analogues to the type 1 IGF receptor determined by BIAcore analysis. Eur J Biochem. 2002;269(3):961-968. DOI: https://doi.org/10.1046/j.0014-2956.2001.02735.x
110. GroPep. GroPep Bioreagents IGF Analogues. Human [Leu27]IGF-II. https://gropep.com/product_families/igf-analogues/products/human-leu27-igf-ii--7
111. Charnock JC, Dilworth MR, Aplin JD, Sibley CP, Westwood M, Crocker IP. The impact of a human IGF-II analog ([Leu27]IGF-II) on fetal growth in a mouse model of fetal growth restriction. American journal of physiology Endocrinology and metabolism. 2016;310(1):E24-31. DOI: https://doi.org/10.1152/ajpendo.00379.2015
112. Sferruzzi-Perri AN, Owens JA, Standen P, Roberts CT. Maternal insulin-like growth factor-II promotes placental functional development via the type 2 IGF receptor in the guinea pig. Placenta. 2008;29(4):347-355. DOI: https://doi.org/10.1016/j.placenta.2008.01.009
113. Okamoto T, Nishimoto I. Analysis of stimulation-G protein subunit coupling by using active insulin-like growth factor II receptor peptide. Proc Natl Acad Sci U S A. 1991;88(18):8020-8023. DOI: https://doi.org/10.1073/pnas.88.18.8020
114. Higashijima T, Uzu S, Nakajima T, Ross EM. Mastoparan, a peptide toxin from wasp venom, mimics receptors by activating. The Journal of biological chemistry. 1988;263(14):6491-6494.
115. Okamoto T, Katada T, Murayama Y, Ui M, Ogata E, Nishimoto I. A simple structure encodes G protein-activating function of the IGF-II/mannose. Cell. 1990;62(4):709-717. DOI: https://doi.org/10.1016/0092-8674(90)90116-v
116. Wang KCW, Tosh DN, Zhang S, et al. IGF-2R-Galphaq signaling and cardiac hypertrophy in the low-birth-weight lamb. Am J Physiol Regul Integr Comp Physiol. 2015;308(7):R627-635. DOI: https://doi.org/10.1152/ajpregu.00346.2014
117. Wang KCW, Brooks DA, Botting KJ, Morrison JL. IGF-2R-mediated signaling results in hypertrophy of cultured cardiomyocytes from fetal sheep. Biology of reproduction. 2012;86(6):183. DOI: https://doi.org/10.1095/biolreprod.112.100388
118. Chen R-J, Wu H-C, Chang M-H, et al. Leu27IGF2 plays an opposite role to IGF1 to induce H9c2 cardiomyoblast cell apoptosis via Galphaq signaling. J Mol Endocrinol. 2009;43(6):221-230. DOI: https://doi.org/10.1677/JME-08-0121
119. Harris LK, Crocker IP, Baker PN, Aplin JD, Westwood M. IGF2 actions on trophoblast in human placenta are regulated by the insulin-like growth factor 2 receptor, which can function as both a signaling and clearance receptor. Biology of reproduction. 2011;84(3):440-446. DOI: https://doi.org/10.1095/biolreprod.110.088195
120. Pang Z-J, Xing F-Q. Expression of transforming growth factor-β and insulin-like growth factor in molar and placental tissues. Archives of Gynecology and Obstetrics. 2003;269(1):1-4. DOI: https://doi.org/10.1007/s00404-002-0379-3
121. Bolat F, Haberal N, Tunali N, Aslan E, Bal N, Tuncer I. Expression of vascular endothelial growth factor (VEGF), hypoxia inducible factor 1 alpha (HIF-1α), and transforming growth factors β1 (TGFβ1) and β3 (TGFβ3) in gestational trophoblastic disease. Pathology - Research and Practice. 2010;206(1):19-23. DOI: https://doi.org/10.1016/j.prp.2009.07.017
122. Dehaghani AS, Rad NR, Fattahi MJ, et al. Investigation of soluble HER2 and transforming growth factor Beta-1 serum levels in gestational trophoblastic disease. Pathol Oncol Res. 2009;15(1):37-40. DOI: https://doi.org/10.1007/s12253-008-9115-z
123. Xu G, Chakraborty C, Lala PK. Expression of TGF-β Signaling Genes in the Normal, Premalignant, and Malignant Human Trophoblast: Loss of Smad3 in Choriocarcinoma Cells. Biochemical and Biophysical Research Communications. 2001;287(1):47-55. DOI: http://dx.doi.org/10.1006/bbrc.2001.5533
124. Xu G, Chakraborty C, Lala PK. Restoration of TGF-β regulation of plasminogen activator inhibitor-1 in Smad3-restituted human choriocarcinoma cells. Biochemical and Biophysical Research Communications. 2002;294(5):1079-1086. DOI: https://doi.org/10.1016/S0006-291X(02)00605-8
125. Xu G, Chakraborty C, Lala PK. Reconstitution of Smad3 restores TGF-β response of tissue inhibitor of metalloprotease-1 upregulation in human choriocarcinoma cells. Biochemical and Biophysical Research Communications. 2003;300(2):383-390. DOI: http://dx.doi.org/10.1016/S0006-291X(02)02845-0
126. Lafontaine L, Chaudhry P, Lafleur MJ, Van Themsche C, Soares MJ, Asselin E. Transforming growth factor Beta regulates proliferation and invasion of rat placental cell lines. Biol Reprod. 2011;84(3):553-559. DOI: https://doi.org/10.1095/biolreprod.110.086348
127. Syed V. TGF-β Signaling in Cancer. Journal of Cellular Biochemistry. 2016;117(6):1279-1287. DOI: https://doi.org/10.1002/jcb.25496
128. Li Y, Xu Q, Zhang Z, Liu S, Shi C, Tan Y. The impact of TGF-β1 on the mRNA expression of TβR I, TβR II, Smad4 and the invasiveness of the JEG-3 placental choriocarcinoma cell line. Oncology Letters. 2012;4(6):1344-1348. DOI: https://doi.org/10.3892/ol.2012.906
129. Wolf N, Yang W, Dunk CE, et al. Regulation of the Matricellular Proteins CYR61 (CCN1) and NOV (CCN3) by Hypoxia-Inducible Factor-1α and Transforming-Growth Factor-β3 in the Human Trophoblast. Endocrinology. 2010;151(6):2835-2845. DOI: https://doi.org/10.1210/en.2009-1195
130. Papadimitriou E, Kardassis D, Moustakas A, Stournaras C. TGFbeta-induced early activation of the small GTPase RhoA is Smad2/3-independent and involves Src and the guanine nucleotide exchange factor Vav2. Cell Physiol Biochem. 2011;28(2):229-238. DOI: https://doi.org/10.1159/000331734
131. Vardouli L, Vasilaki E, Papadimitriou E, Kardassis D, Stournaras C. A novel mechanism of TGFβ-induced actin reorganization mediated by Smad proteins and Rho GTPases. The FEBS Journal. 2008;275(16):4074-4087. DOI: https://doi.org/10.1111/j.1742-4658.2008.06549.x
132. Xu Q, Tan Y, Zhang K, Li Y. Crosstalk between p38 and Smad3 through TGF-beta1 in JEG-3 choriocarcinoma cells. Int J Oncol. 2013;43(4):1187-1193. DOI: https://doi.org/10.3892/ijo.2013.2026
133. Tan Y, Xu Q, Li Y, Mao X, Zhang K. Crosstalk between the p38 and TGF-β signaling pathways through TβRI, TβRII and Smad3 expression in plancental choriocarcinoma JEG-3 cells. Oncology Letters. 2014;8(3):1307-1311. DOI: https://doi.org/10.3892/ol.2014.2255
134. Tufegdzic Vidakovic A, Rueda OM, Vervoort SJ, et al. Context-Specific Effects of TGF-beta/SMAD3 in Cancer Are Modulated by the Epigenome. Cell Rep. 2015;13(11):2480-2490. DOI: https://doi.org/10.1016/j.celrep.2015.11.040
135. Bai J, Xi Q. Crosstalk between TGF-beta signaling and epigenome. Acta Biochim Biophys Sin (Shanghai). 2018;50(3):322. DOI: https://doi.org/10.1093/abbs/gmy001
136. Cardenas H, Vieth E, Lee J, et al. TGF-beta induces global changes in DNA methylation during the epithelial-to-mesenchymal transition in ovarian cancer cells. Epigenetics. 2014;9(11):1461-1472. DOI: https://doi.org/10.4161/15592294.2014.971608
137. Singh V, Singh AP, Sharma I, et al. Epigenetic deregulations of Wnt/beta-catenin and transforming growth factor beta-Smad pathways in esophageal cancer: Outcome of DNA methylation. J Cancer Res Ther. 2019;15(1):192-203. DOI: https://doi.org/10.4103/jcrt.JCRT_634_17
138. Suriyamurthy S, Baker D, Ten Dijke P, Iyengar PV. Epigenetic Reprogramming of TGF-beta Signaling in Breast Cancer. Cancers (Basel). 2019;11(5). DOI: https://doi.org/10.3390/cancers11050726
139. Lee C, Zhang Q, Zi X, et al. TGF-beta mediated DNA methylation in prostate cancer. Transl Androl Urol. 2012;1(2):78-88. DOI: https://doi.org/10.3978/j.issn.2223-4683.2012.05.06
140. Morales E, Vilahur N, Salas LA, et al. Genome-wide DNA methylation study in human placenta identifies novel loci associated with maternal smoking during pregnancy. Int J Epidemiol. 2016;45(5):1644-1655. DOI: https://doi.org/10.1093/ije/dyw196
141. Mandal C, Halder D, Jung KH, Chai YG. Gestational Alcohol Exposure Altered DNA Methylation Status in the Developing Fetus. Int J Mol Sci. 2017;18(7). DOI: https://doi.org/10.3390/ijms18071386
142. Nogues P, Dos Santos E, Jammes H, et al. Maternal obesity influences expression and DNA methylation of the adiponectin and leptin systems in human third-trimester placenta. Clin Epigenetics. 2019;11(1):20. DOI: https://doi.org/10.1186/s13148-019-0612-6
143. Daniels TE, Sadovnikoff AI, Ridout KK, Lesseur C, Marsit CJ, Tyrka AR. Associations of maternal diet and placenta leptin methylation. Mol Cell Endocrinol. 2020;505:110739. DOI: https://doi.org/10.1016/j.mce.2020.110739
144. Workalemahu T, Ouidir M, Shrestha D, Wu J, Grantz KL, Tekola-Ayele F. Differential DNA Methylation in Placenta Associated With Maternal Blood Pressure During Pregnancy. Hypertension. 2020;75(4):1117-1124. DOI: https://doi.org/10.1161/HYPERTENSIONAHA.119.14509
145. Santos HP, Jr., Bhattacharya A, Martin EM, et al. Epigenome-wide DNA methylation in placentas from preterm infants: association with maternal socioeconomic status. Epigenetics. 2019;14(8):751-765. DOI: https://doi.org/10.1080/15592294.2019.1614743
146. Dwi Putra SE, Reichetzeder C, Hasan AA, et al. Being Born Large for Gestational Age is Associated with Increased Global Placental DNA Methylation. Sci Rep. 2020;10(1):927. DOI: https://doi.org/10.1038/s41598-020-57725-0
147. Clarkson-Townsend DA, Everson TM, Deyssenroth MA, et al. Maternal circadian disruption is associated with variation in placental DNA methylation. PLoS One. 2019;14(4):e0215745. DOI: https://doi.org/10.1371/journal.pone.0215745
148. Schuster J, Uzun A, Stablia J, Schorl C, Mori M, Padbury JF. Effect of prematurity on genome wide methylation in the placenta. BMC Med Genet. 2019;20(1):116. DOI: https://doi.org/10.1186/s12881-019-0835-6
149. Petropoulos S, Guillemin C, Ergaz Z, et al. Gestational Diabetes Alters Offspring DNA Methylation Profiles in Human and Rat: Identification of Key Pathways Involved in Endocrine System Disorders, Insulin Signaling, Diabetes Signaling, and ILK Signaling. Endocrinology. 2015;156(6):2222-2238. DOI: https://doi.org/10.1210/en.2014-1643
150. Hillman SL, Finer S, Smart MC, et al. Novel DNA methylation profiles associated with key gene regulation and transcription pathways in blood and placenta of growth-restricted neonates. Epigenetics. 2015;10(1):50-61. DOI: https://doi.org/10.4161/15592294.2014.989741
151. Finer S, Mathews C, Lowe R, et al. Maternal gestational diabetes is associated with genome-wide DNA methylation variation in placenta and cord blood of exposed offspring. Hum Mol Genet. 2015;24(11):3021-3029. DOI: https://doi.org/10.1093/hmg/ddv013
152. Chu T, Bunce K, Shaw P, et al. Comprehensive analysis of preeclampsia-associated DNA methylation in the placenta. PLoS One. 2014;9(9):e107318. DOI: https://doi.org/10.1371/journal.pone.0107318
153. Anton L, Brown AG, Bartolomei MS, Elovitz MA. Differential methylation of genes associated with cell adhesion in preeclamptic placentas. PLoS One. 2014;9(6):e100148. DOI: https://doi.org/10.1371/journal.pone.0100148
154. Jia RZ, Zhang X, Hu P, et al. Screening for differential methylation status in human placenta in preeclampsia using a CpG island plus promoter microarray. Int J Mol Med. 2012;30(1):133-141. DOI: https://doi.org/10.3892/ijmm.2012.983
155. Ruchat SM, Houde AA, Voisin G, et al. Gestational diabetes mellitus epigenetically affects genes predominantly involved in metabolic diseases. Epigenetics. 2013;8(9):935-943. DOI: https://doi.org/10.4161/epi.25578
156. Lambertini L, Lee TL, Chan WY, et al. Differential methylation of imprinted genes in growth-restricted placentas. Reprod Sci. 2011;18(11):1111-1117. DOI: https://doi.org/10.1177/1933719111404611
157. Banister CE, Koestler DC, Maccani MA, Padbury JF, Houseman EA, Marsit CJ. Infant growth restriction is associated with distinct patterns of DNA methylation in human placentas. Epigenetics. 2011;6(7):920-927. DOI: https://dx.doi.org/10.4161%2Fepi.6.7.16079
158. Blair JD, Yuen RK, Lim BK, McFadden DE, von Dadelszen P, Robinson WP. Widespread DNA hypomethylation at gene enhancer regions in placentas associated with early-onset pre-eclampsia. Mol Hum Reprod. 2013;19(10):697-708. DOI: https://doi.org/10.1093/molehr/gat044
159. El Hajj N, Pliushch G, Schneider E, et al. Metabolic programming of MEST DNA methylation by intrauterine exposure to gestational diabetes mellitus. Diabetes. 2013;62(4):1320-1328. DOI: https://doi.org/10.2337/db12-0289
160. Howe CG, Cox B, Fore R, et al. Maternal Gestational Diabetes Mellitus and Newborn DNA Methylation: Findings From the Pregnancy and Childhood Epigenetics Consortium. Diabetes Care. 2020;43(1):98-105. DOI: https://doi.org/10.2337/dc19-0524
161. Rong C, Cui X, Chen J, Qian Y, Jia R, Hu Y. DNA methylation profiles in placenta and its association with gestational diabetes mellitus. Exp Clin Endocrinol Diabetes. 2015;123(5):282-288. DOI: https://doi.org/10.1055/s-0034-1398666
162. Weng X, Liu F, Zhang H, et al. Genome-wide DNA methylation profiling in infants born to gestational diabetes mellitus. Diabetes Res Clin Pract. 2018;142:10-18. DOI: https://doi.org/10.1016/j.diabres.2018.03.016
163. Elliott HR, Sharp GC, Relton CL, Lawlor DA. Epigenetics and gestational diabetes: a review of epigenetic epidemiology studies and their use to explore epigenetic mediation and improve prediction. Diabetologia. 2019;62(12):2171-2178. DOI: https://doi.org/10.1007/s00125-019-05011-8
164. Hivert MF, Cardenas A, Allard C, et al. Interplay of Placental DNA Methylation and Maternal Insulin Sensitivity in Pregnancy. Diabetes. 2020;69(3):484-492. DOI: https://doi.org/10.2337/db19-0798
165. Cardenas A, Gagne-Ouellet V, Allard C, et al. Placental DNA Methylation Adaptation to Maternal Glycemic Response in Pregnancy. Diabetes. 2018;67(8):1673-1683. DOI: https://doi.org/10.2337/db18-0123
166. Mousa AA, Archer KJ, Cappello R, et al. DNA methylation is altered in maternal blood vessels of women with preeclampsia. Reprod Sci. 2012;19(12):1332-1342. DOI: https://doi.org/10.1177/1933719112450336
167. Yeung KR, Chiu CL, Pidsley R, Makris A, Hennessy A, Lind JM. DNA methylation profiles in preeclampsia and healthy control placentas. Am J Physiol Heart Circ Physiol. 2016;310(10):H1295-1303. DOI: https://doi.org/10.1152/ajpheart.00958.2015
168. Demond H, Anvar Z, Jahromi BN, et al. A KHDC3L mutation resulting in recurrent hydatidiform mole causes genome-wide DNA methylation loss in oocytes and persistent imprinting defects post-fertilisation. Genome Med. 2019;11(1):84. DOI: https://doi.org/10.1186/s13073-019-0694-y
169. Xiao X, Zhao Y, Jin R, et al. Fetal growth restriction and methylation of growth-related genes in the placenta. Epigenomics. 2016;8(1):33-42. DOI: https://doi.org/10.2217/epi.15.101
170. Thompson RF, Fazzari MJ, Niu H, Barzilai N, Simmons RA, Greally JM. Experimental intrauterine growth restriction induces alterations in DNA methylation and gene expression in pancreatic islets of rats. J Biol Chem. 2010;285(20):15111-15118. DOI: https://doi.org/10.1074/jbc.M109.095133
171. Hu Y, Hu L, Gong D, et al. Genome-wide DNA methylation analysis in jejunum of Sus scrofa with intrauterine growth restriction. Mol Genet Genomics. 2018;293(4):807-818. DOI: https://doi.org/10.1007/s00438-018-1422-9
172. Einstein F, Thompson RF, Bhagat TD, et al. Cytosine methylation dysregulation in neonates following intrauterine growth restriction. PLoS One. 2010;5(1):e8887. DOI: https://doi.org/10.1371/journal.pone.0008887
173. Roifman M, Choufani S, Turinsky AL, et al. Genome-wide placental DNA methylation analysis of severely growth-discordant monochorionic twins reveals novel epigenetic targets for intrauterine growth restriction. Clin Epigenetics. 2016;8:70. DOI: https://doi.org/10.1186/s13148-016-0238-x
174. Chabrun F, Huetz N, Dieu X, et al. Data-Mining Approach on Transcriptomics and Methylomics Placental Analysis Highlights Genes in Fetal Growth Restriction. Front Genet. 2019;10:1292. DOI: https://doi.org/10.3389/fgene.2019.01292
175. Smith ZD, Shi J, Gu H, et al. Epigenetic restriction of extraembryonic lineages mirrors the somatic transition to cancer. Nature. 2017;549(7673):543-547. DOI: https://doi.org/10.1038/nature23891
176. Nordor AV, Nehar-Belaid D, Richon S, et al. The early pregnancy placenta foreshadows DNA methylation alterations of solid tumors. Epigenetics. 2017;12(9):793-803. DOI: https://doi.org/10.1080/15592294.2017.1342912