Prenatal Stress and Endo-crine Disrupting Chemical Exposure: Hypothalamic-Pituitary-Adrenal Axis Dysregulation as a Mecha-nism for the Health Conse-quences of Both
Main Article Content
Abstract
During the past several decades there has been increasing attention to the risks of exposure to endocrine disrupting chemicals, agents that mimic or block the effects of endogenous hormones. Previous research demonstrates that there may be critical periods of development where factors such as prenatal stress and endocrine disrupting chemical exposure can result in endocrine system dysregulation which manifests both immediately and later in life. This review describes the types of common endocrine disrupting chemicals and routes of exposure, the structure and functions of the hypothalamic-pituitary-adrenal axis and its role in the physiological response to stress, and highlights the current evidence showing that endocrine disrupting chemicals may alter normal hypothalamic-pituitary-adrenal axis functions. These topics are unified upon discussion of evidence indicating that prenatal endocrine disrupting chemical exposure has many of the same effects as prenatal stress on the hypothalamic-pituitary-adrenal axis, leading to long-term dysregulation of the axis and subsequent alterations in physiological responses to stress. We further suggest that prenatal endocrine disrupting chemical exposure in combination with prenatal stress may result in additive, if not synergistic effects on the hypothalamic-pituitary-adrenal axis-mediated stress response. Finally, we discuss vulnerable populations at an elevated risk for dual stress and endocrine disrupting chemical exposure and emphasize critical areas for future research.
Keywords:
Prenatal stress, EDC, HPA axis, cortisol, BPA, poverty
Article Details
How to Cite
HALL, Julianne M.; MERCUGLIANO, Christina; CONTI, Lisa H..
Prenatal Stress and Endo-crine Disrupting Chemical Exposure: Hypothalamic-Pituitary-Adrenal Axis Dysregulation as a Mecha-nism for the Health Conse-quences of Both.
Medical Research Archives, [S.l.], v. 11, n. 6, june 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3985>. Date accessed: 16 may 2024.
doi: https://doi.org/10.18103/mra.v11i6.3985.
Section
Research 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. La Merrill MA, Vandenberg LN, Smith MT, Goodson W, Browne P, Patisaul HB, Guyton KZ, Kortenkamp A, Cogliano, VJ, Woodruff TJ, Rieswijkl L, Sone H, Korach KS, Gore AC, Zeise L, Zoller RT. Consensus on the key characteris-tics of endocrine-disrupting chemicals as a ba-sis for hazard identification. Nat Rev Endo-crinol. 2020;16:45-57.
2. Gore AC, Chappell VA, Fenton SE, Flaws JA, Nadal A, Prins GS, Toppari J, Zoller RT. EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemi-cals. Endocrinol Rev. 2015;36: E1-E150.
3. Gore AC, Heindel JJ, Zoeller RT. Endocrine disruption for endocrinologists (and oth-ers). Endocrinology. 2006;147(6 Suppl): S1-S3.
4. Giesbrecht GF, Ejaredar M, Liu J, Thomas J, Letourneau N, Campbell T, Martin JW, Dewey D. Prenatal bisphenol a exposure and dysreg-ulation of infant hypothalamic-pituitary-adrenal axis function: findings from the APrON cohort study. Environ Health. 2017;16:47.
5. Woodruff TJ, Zota AR, Schwartz JM. Environ-mental chemicals in pregnant women in the United States: NHANES 2003-2004. Environ Health Perspect. 2011;116:878-885.
6. Padula AM, Monk C, Brennan PA, Borders A, Barrett ES, McEvoy CT, Foss S, Desai P, Al-shawabkeh A, Wurth R, Salafia C, Fichorova R, Varshavsky J, Kress A, Woodruff TJ, Morel-lo-Frosch R. Maternal prenatal exposures to environmental chemicals and psychosocial stressors-implications for research on perinatal outcomes in the ECHO program – implications for research on perinatal outcomes. J Perina-tol. 2020;40:10-24.
7. DiGangi, J.; Schettler, T.; Cobbing, M.; Rossi, M. Aggregate Exposures to Phthalates in Hu-mans; Health Care Without Harm: Washing-ton, DC, USA, 2002; p. 50.
8. De Kloet, ER., Joels, M., Holsboer, F. Stress and the brain: From adaptation to disease. Nature Rev Neurosci. 2005;6:463-475.
9. Gold, PW., Chrousos GP. Organization of the stress system and its regulation in melancholic and atypical depression: high vs low CRH/NE states. Mol Psychiat. 2002;7:254-275.
10. Dedic, N., Chen, A., Deussing (2018). The CRF family of neuropeptides and their receptors – mediators of the central stress response. Curr Mol Pharmacol. 2018;11:4-31.
11. McEwen BS, Gianaros PJ. Central role of the brain in stress and adaptation: Links to socio-economic status, health, and disease. Ann NY Acad Sci. 2010;1186:190-222.
12. Vale W, Spiess J, Rivier C, Rivier J. Character-ization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotro-pin and beta-endorphin. Science. 1981;213:1394-1397.
13. Rivier C, Vale W. Modulation of stress-induced ACTH release by corticotropin-releasing fac-tor, catecholamines and vasopressin. Nature. 1983;305:325-327.
14. Mbiydzenyuy NE, Hemmings SMJ, Qulu L. Prenatal maternal stress and offspring aggres-sive behavior: Intergenerational and transgenerational inheritance. Front Behav Neurosci. 2022; 16:977416.
15. Timmermans S, Souffriau J, Libert C. A general introduction to glucocorticoid biology. Front Immunol. 2019;10:1545.
16. De Kloet ER, Reul JMHM. Feedback action and tonic influence of corticosteroids on brain func-tion: A concept arising from the heterogeneity of brain receptor systems. Psychoneuroendo-crinol. 1987;12:83-105.
17. Smith SM, Vale WW. The role of the hypotha-lamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues Clin Neurosci. 2006;8:383-395.
18. Moisiadis VG, Matthews SG. Glucocorticoids and fetal programming 1: outcomes. Nat Rev Endocrinol. 2014;10:391-402.
19. Zhang C, Xu D, MacKay H, Abizaid A. A plu-rality of molecular targets: The receptor eco-system for bisphenol-A (BPA). Horm Behav. 2018;101:59-67.
20. Nicolaides NC, Kyratzi E., Lamprokostopoulou A, Chousos GP, Charmandari E. Stress, the stress system and the role of glucocorticoids. Neuroimmunomod. 2015;22:6-19.
21. Kazakou P, Nicolaides NC, Chrousos GP. Basic concepts and hormonal regulators of the stress system. Horm Res Pediatr. 2023;96:8-16.
22. Brunton PJ. Effects of maternal exposure to social stress during pregnancy: consequences for mother and offspring. Reproduc. 2013;146:175-189.
23. Creutzberg KC, Sanson A, Viola TW,Marchisella F, Begni V, Grassi-Oliveira R, Riva MA. Long-lasting effects of prenatal stress on HPA axis and inflammation: A sys-tematic review and multilevel meta-analysis in rodent studies. Neurosci Biobehav Rev. 2021;127:270-283.
24. Harris A, Seckle J. Glucocorticoids, prenatal stress and the programming of disease. Horm Behav. 2011;59:279-289.
25. Howland MA, Sandman CA, Glynn LM. Devel-opmental origins of the human hypothalamic-pituitary-adrenal axis. Expert Rev Endocrinol Metab. 2017;12:321-339.
26. Ruffaner-Hanson C, Noor S, Sun MS, Solomon E, Enriquez Marquez L., Rodriguez DE, Allan AM, Caldwell KK, Bakhireva LN, Milligan ED. The maternal-placental-fetal interface: Adaptations of the HPA axis and immune me-diators following maternal stress and prenatal alcohol. Exper Neurol. 2022;355:114121.
27. Constantinof A, Moisiadis VG, Matthews SG. Programming of stress pathways: A transgen-erational perspective. J Ster Biochem Mol Biol. 2016;160:175-180.
28. Moisiadis VG, Matthews SG. Glucocorticoids and fetal programming part 2: mechanisms. Nat Rev Endocrinol. 2014;10:403-411.
29. Abe H, Hidaka N, Kawagoe C, Odagiri K, Watanabe Y, Ikeda T, Ishizuka Y, Hashiguchi H, Takeda R, Nishimori T, Ishida Y. Prenatal psychological stress causes higher emotionali-ty, depression-like behavior, and elevated ac-tivity in the hypothalamic-pituitary-adrenal axis. Neurosci Res. 2007;59:145-151.
30. Bosch O, Much W, Bredewold R, Slattery DA, Neumann ID. Prenatal stress increases HPA ax-is activity and impairs maternal care in lactat-ing female offspring: Implications for postpar-tum mood disorder. Psychoneuroendocrinol. 2007;32:267-278.
31. Brunton PJ, Russell JA. Prenatal social stress in the rat programmes neuroendocrine and be-havioral responses to stress in the adult off-spring: Sex-specific effects. J Neuroendocrinol. 2010;22:258-271.
32. Henry C, Kabbaj M, Simon H, Le Moal M, Maccari S. Prenatal stress increases the hypo-thalamic-pituitary-adrenal axis response in young and adult rats. J Neuroendocrinol. 1994;6:341-345.
33. Jafari Z, Mehla J, Kolb BE, Moharjerani MH. Prenatal noise stress impairs HPA axis and cognitive performance in mice. Scientific Rep. 2017;7:10560.
34. Mueller BR, Bale TL. Sex-specific programming of offspring emotionality after stress early in pregnancy. J Neurosci. 2008;28:9055-9065.
35. Sanchez MM, McCormack K, Grand AP, Fulks R, Graff A, Maestripieri D. Effects of sex and early maternal abuse on adrenocorticotropin hormone and cortisol responses to the cortico-tropin-releasing hormone challenge during the first 3 years of life in group-living rhesus mon-keys. Dev Psychopathol. 2010; 22:45-53.
36. Weinstock M, Matlina E, Maor GI, Rosen H, McEwen BS. Prenatal stress selectively alters the reactivity of the hypothalamic-pituitary adren-al system in the female rat. Brain Res. 1992; 595:195-200.
37. McLean MA, Simcock G, Elgbeili G, Laplante DP, Kildea S, Hurrion E, Lequertier B, Cobham VE, King S. Disaster-related prenatal maternal stress, and childhood HPA-axis regulation and anxiety: The QF2011 Queensland flood study. Psychoneuroendocrinol. 2020;118:104716.
38. Bosch OJ, Kromer SA, Neumann ID. Prenatal stress: opposite effects on anxiety and hypo-thalamic expression of vasopressin and corti-cotropin-releasing hormone in rats selectively bred for high and low anxiety. Eur J Neurosci. 2006;23:541-551.
39. Piviana SG, Rakitskaya VV, Akulova VK, Ordyan NE. Activity of the hypothalamic-pituitary-adrenal system in prenatally stress male rats on the experimental model of post-traumatic stress disorder. Bull Exper Biol Med. 2016;160:601-604.
40. Fan JM, Chen XQ, Jin H, Du JZ. Gestational hypoxia alone or combined with restraint sen-sitizes the hypothalamic-pituitary-adrenal axis and induces anxiety-like behavior in adult male rat offspring. Neurosci. 2009;159:1363-1373.
41. Jezova D, Skultetyova I, Makatsori A, Moncek F, Duncko R. Hypothalamic-pituitary-adrenocortical axis function and hedonic be-havior in adult male and female rats prenatal-ly stressed by maternal food restriction. Stress. 2002;5:177-183.
42. Wang X, Meng FS, Liu ZY, Fan JM, Hao K, Chen XQ, Du JZ. Gestational hypoxia induces sex-differential methylation of Crh1 linked to anxiety behavior. Mol Neurobiol. 2013;48:544-555.
43. Zohar I, Weinstock M. Differential effect of prenatal stress on the expression of corticotro-pin-releasing hormone and its receptors in the hypothalamus and amygdala of male and fe-male mice. J Neuroendocrinol. 2011;23:320-328.
44. Maccari S, Kruger HJ, Morley-Fletcher S, Szyf M, Brunton PJ. The consequences of early-life adversity: Neurobiological, behavioral and epigenetic adaptations. J Neuroendocrinol. 2014;26:707-723.
45. Lautarescu A, Craig MC, Glover V. Prenatal stress: Effects on fetal and child brain devel-opment. Int Rev Neurobiol. 2020;150:17-40.
46. Cottrell EC, Seckl JR. Prenatal stress, glucocor-ticoids and the programming of adult disease. Front Behav Neurosci. 2009; 3:article 19.
47. Barbazanges A, Piazza PV, Le Moal M, Mac-cari S. Maternal glucocorticoid secretion me-diates long-term effects of prenatal stress. J Neurosci. 1996;16:3943-3949.
48. McEwen BS. Stress and hippocampal plasticity. Ann Rev Neurosci. 1999;22:105-122.
49. Shoener JA, Baig R, Page KC. Prenatal expo-sure to dexamethasone alters hippocampal drive on hypothalamic-pituitary adrenal axis activity in adult male rats. Am J Physiol Regul Integr Comp Physiol. 2006;290:R1366-R1373.
50. Szuran T, Pliska V, Pokorny J, Welzl H. Prena-tal stress in rats: Effects on plasma corti-costerone, hippocampal glucocorticoid recep-tors, and maze performance. Physiol Behav. 2000;71:353-362.
51. Welberg LAM, Seckl JR, Holmes MC. Prenatal glucocorticoid programming of brain cortico-steroid receptors and corticotrophin-releasing hormone: Possible implications for behavior. Neurosci. 2001;104:71-79.
52. Pascuan CG, Di Rosso ME, Pivoz-Avedikian JE, Wald MR, Zorrilla Zubilete MA, Genaro AM. Alteration of neurotrophin and cytokine ex-pression in lymphocytes as novel markers of spatial memory deficits induced by prenatal stress. Physiol Behav. 2017;173:144-155.
53. Liao L, Yao X, Huang J, Bai S. Prenatal stress up-regulated hippocampal glucocorticoid re-ceptor expression in female adult rat off-spring. Int J Morphol. 202;36:400-405.
54. Ward HE, Johnson EA, Salm AK, Birkle DL. Ef-fects of prenatal stress on defensive with-drawal behavior and corticotropin releasing factor systems in rat brain. Physiol Behav. 2000;70:359-366.
55. Cratty MS, Ward HE, Johnson EA, Azzaro AJ, Birkle DL. Prenatal stress increases corticotro-pin-releasing factor (CRF) content and release from rat amygdala minces. Brain Res. 1995;675:297-302.
56. Bale TL. Epigenetic and transgenerational re-programming of brain development. Nat Rev Neurosci. 2015;16:332-344.
57. Glover V, O’Connor TG, O’Donnell K. Prenatal stress and the programming of the HPA axis. Neurosci Biobehav Rev. 2010;35:17-22.
58. Palma-Gudiel H, Cordova-Palomera A, Eix-arch E, Deuschle M, Fananas L. Maternal psy-chological stress during pregnancy alters the epigenetic signature of the glucocorticoid re-ceptor gene promotor in their offspring: a me-ta analysis. Epigenetics. 2015;10:893-902.
59. Hamada H, Matthews SG. Prenatal program-ming of stress responsiveness and behaviours: Progress and perspectives. J Neuroendocrinol. 2018;31:e12674.
60. McGowan PO, Matthews SG. Prenatal stress, glucocorticoids, and developmental program-ming of the stress response. Endocrinol. 2018;159:69-83.
61. Gray JD, Kogan JF, Marrocco J, McEwen BS. Genomic and epigenetic mechanisms of gluco-corticoids in the brain. Nature Rev Endocrinol. 2017;13:661-673.
62. McEwen BS. Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev. 2007;87:873-904.
63. Lv Y, Chen P, Kuang L, Han Z, Solanki B, Zhou W, Tao F, Chen R, Yao Y. Role of corticotro-pin-releasing hormone in the impact of chronic stress during pregnancy on inducing depres-sion in male offspring mice. Brain Res. 2020;1747:147029.
64. Grundwald NJ, Brunton PJ. Prenatal stress programs neuroendocrine stress responses and affective behaviors in second generation rats in a sex-dependent manner. Psychoneuroen-docrinol. 2015;62:204-216.
65. Mathey LIP. Neuroendocrinology of pregnan-cy: participation of sex hormones. In Marsh, C. (Ed.). (2021). Reproductive Hormones. IntechOpen. doi: 10.5772/intechopen.91499
66. Walley SN, Roepke TA. Perinatal exposure to endocrine disrupting compounds and the con-trol of feeding behavior-An overview. Horm Behav. 2018;101:22-28.
67. Martinez-Arguelles DB, Papadopoulos V. Mechanisms mediating environmental chemi-cal-induced endocrine disruption in the adren-al gland. Front Endocrinol. 2015;6:article 29.
68. MacKay H, Abizaid A. A plurality of molecular targets: The receptor ecosystem for bisphenol-A (BPA). Horm Behav. 2018;101:59-67.
69. Nesan D, Sewell LC, Kurrasch DM. Opening the black box of endocrine disruption of brain development: Lessons from the characteriza-tion of Bisphenol A. Horm Behav. 2018;101:50-58.
70. Panagiotidou E, Zerva S, Mitsiou DJ, Alexis MN, Kitraki E. Perinatal exposure to low-dose bisphenol A affects the neuroendocrine stress response in rats. J Endocrinol. 2014;220(3):207-218.
71. Poimenova A, Markaki E, Rahiotis C, Kitraki E. Corticosterone-regulated actions in the rat brain are affected by perinatal exposure to low dose of bisphenol A. Neurosci. 2010;167(3):741-749.
72. Zimmer KE, Gutleb AC, Lyche JL, Dahl E, Osham IC, Krogenaes A, Skaare JU, Ropstad E. Altered stress-induced cortisol levels in goats exposed to polychlorinated biphenyls (PCB 126 and PCB 153) during fetal and postnatal development. J Toxicol Environ Health A. 2009;72(3-4):164-172.
73. Reilly MP, Weeks CD, Topper VY, Thompson LM, Crews D, Gore AC. The effects of prenatal PCBs on adult social behavior in rats. Horm Behav. 2015;73:47-55.
74. Salgado-Freiria R, Lopez-Doval S, Lafuente A. Perfluorooctane sulfonate (PFOS) can alter the hypothalamic-pituitary-adrenal (HPA) axis ac-tivity by modifying CRF1 and glucocorticoid receptors. Tox Lett. 2018;295:1-9.
75. Harris EP, Allardice HA, Schenk AK, Rissman EF. Effects of maternal or paternal bisphenol A exposure on offspring behavior. Horm Behav. 2018;101:68-76.
76. Wiersielis KR, Samuels BA, Roepke TA. Perina-tal exposure to bisphenol A at the intersection of stress, anxiety and depression. Neurotox Teratol. 2020; 79:106884.
77. Sobolewski M, Conrad K, Marvin E, Allen JL, Cory-Slechta DA. Endocrine active metals, prenatal stress and enhanced neurobehavioral disruption. Horm Behav. 2018;101:36-49.
78. Jacobs MN, Marczylo EL, Guerrero-Bosagna C, Ruegg J. Marked for life: Effects of endo-crine disrupting chemicals. Ann Rev Environ Re-sour. 2017;42:105-160.
79. Streifer M, Core AC. Epigenetics, estrogenic endocrine-disrupting chemicals (EDCs) and the brain. Advan Pharmacol. 2021;92:73-99.
80. Van Cauwenbergh O, Di Serafino A, Tygat J, Soubry A. Transgenerational epigenetic ef-fects from male exposure to endocrine-disrupting compounds: a systematic review on research in mammals. Clin Epigenet. 2020;12:65
81. Anway MD, Skinner MK. Epigenetic transgen-erational actions of endocrine disruptors. En-docrionol. 2006;Suppl:S430S49.
82. Di Criscio M, Ekholm Lodahl J, Stamatakis A, Kitraki E, Bakoyiannis I, Repouskou A, Bornehag CG, Gennings C, Lupu D, Ruegg J. A human-relevant mixture of endocrine disrupt-ing chemicals induces changes in hippocampal DNA methylation correlating with hyperactive behavior in male mice. Chemosphere. 2023;313:137633.
83. Stein LJ, Gunier RB, Harley K, Kogut K, Brad-man A, Eskenazi B. Early childhood adversity potentiates the adverse association between prenatal organophosphate pesticide exposure and child IQ: The CHAMACOS cohort. Neuro-toxicol. 2016;56:180–7.
84. Huang J, Eskenazi B, Bornman R, Rauch S, Chevrier J. Maternal Peripartum Serum DDT/E and Urinary Pyrethroid Metabolite Concentra-tions and Child Infections at 2 Years in the VHEMBE Birth Cohort. Environ Health Perspect. 2018;126:067006.
2. Gore AC, Chappell VA, Fenton SE, Flaws JA, Nadal A, Prins GS, Toppari J, Zoller RT. EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemi-cals. Endocrinol Rev. 2015;36: E1-E150.
3. Gore AC, Heindel JJ, Zoeller RT. Endocrine disruption for endocrinologists (and oth-ers). Endocrinology. 2006;147(6 Suppl): S1-S3.
4. Giesbrecht GF, Ejaredar M, Liu J, Thomas J, Letourneau N, Campbell T, Martin JW, Dewey D. Prenatal bisphenol a exposure and dysreg-ulation of infant hypothalamic-pituitary-adrenal axis function: findings from the APrON cohort study. Environ Health. 2017;16:47.
5. Woodruff TJ, Zota AR, Schwartz JM. Environ-mental chemicals in pregnant women in the United States: NHANES 2003-2004. Environ Health Perspect. 2011;116:878-885.
6. Padula AM, Monk C, Brennan PA, Borders A, Barrett ES, McEvoy CT, Foss S, Desai P, Al-shawabkeh A, Wurth R, Salafia C, Fichorova R, Varshavsky J, Kress A, Woodruff TJ, Morel-lo-Frosch R. Maternal prenatal exposures to environmental chemicals and psychosocial stressors-implications for research on perinatal outcomes in the ECHO program – implications for research on perinatal outcomes. J Perina-tol. 2020;40:10-24.
7. DiGangi, J.; Schettler, T.; Cobbing, M.; Rossi, M. Aggregate Exposures to Phthalates in Hu-mans; Health Care Without Harm: Washing-ton, DC, USA, 2002; p. 50.
8. De Kloet, ER., Joels, M., Holsboer, F. Stress and the brain: From adaptation to disease. Nature Rev Neurosci. 2005;6:463-475.
9. Gold, PW., Chrousos GP. Organization of the stress system and its regulation in melancholic and atypical depression: high vs low CRH/NE states. Mol Psychiat. 2002;7:254-275.
10. Dedic, N., Chen, A., Deussing (2018). The CRF family of neuropeptides and their receptors – mediators of the central stress response. Curr Mol Pharmacol. 2018;11:4-31.
11. McEwen BS, Gianaros PJ. Central role of the brain in stress and adaptation: Links to socio-economic status, health, and disease. Ann NY Acad Sci. 2010;1186:190-222.
12. Vale W, Spiess J, Rivier C, Rivier J. Character-ization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotro-pin and beta-endorphin. Science. 1981;213:1394-1397.
13. Rivier C, Vale W. Modulation of stress-induced ACTH release by corticotropin-releasing fac-tor, catecholamines and vasopressin. Nature. 1983;305:325-327.
14. Mbiydzenyuy NE, Hemmings SMJ, Qulu L. Prenatal maternal stress and offspring aggres-sive behavior: Intergenerational and transgenerational inheritance. Front Behav Neurosci. 2022; 16:977416.
15. Timmermans S, Souffriau J, Libert C. A general introduction to glucocorticoid biology. Front Immunol. 2019;10:1545.
16. De Kloet ER, Reul JMHM. Feedback action and tonic influence of corticosteroids on brain func-tion: A concept arising from the heterogeneity of brain receptor systems. Psychoneuroendo-crinol. 1987;12:83-105.
17. Smith SM, Vale WW. The role of the hypotha-lamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues Clin Neurosci. 2006;8:383-395.
18. Moisiadis VG, Matthews SG. Glucocorticoids and fetal programming 1: outcomes. Nat Rev Endocrinol. 2014;10:391-402.
19. Zhang C, Xu D, MacKay H, Abizaid A. A plu-rality of molecular targets: The receptor eco-system for bisphenol-A (BPA). Horm Behav. 2018;101:59-67.
20. Nicolaides NC, Kyratzi E., Lamprokostopoulou A, Chousos GP, Charmandari E. Stress, the stress system and the role of glucocorticoids. Neuroimmunomod. 2015;22:6-19.
21. Kazakou P, Nicolaides NC, Chrousos GP. Basic concepts and hormonal regulators of the stress system. Horm Res Pediatr. 2023;96:8-16.
22. Brunton PJ. Effects of maternal exposure to social stress during pregnancy: consequences for mother and offspring. Reproduc. 2013;146:175-189.
23. Creutzberg KC, Sanson A, Viola TW,Marchisella F, Begni V, Grassi-Oliveira R, Riva MA. Long-lasting effects of prenatal stress on HPA axis and inflammation: A sys-tematic review and multilevel meta-analysis in rodent studies. Neurosci Biobehav Rev. 2021;127:270-283.
24. Harris A, Seckle J. Glucocorticoids, prenatal stress and the programming of disease. Horm Behav. 2011;59:279-289.
25. Howland MA, Sandman CA, Glynn LM. Devel-opmental origins of the human hypothalamic-pituitary-adrenal axis. Expert Rev Endocrinol Metab. 2017;12:321-339.
26. Ruffaner-Hanson C, Noor S, Sun MS, Solomon E, Enriquez Marquez L., Rodriguez DE, Allan AM, Caldwell KK, Bakhireva LN, Milligan ED. The maternal-placental-fetal interface: Adaptations of the HPA axis and immune me-diators following maternal stress and prenatal alcohol. Exper Neurol. 2022;355:114121.
27. Constantinof A, Moisiadis VG, Matthews SG. Programming of stress pathways: A transgen-erational perspective. J Ster Biochem Mol Biol. 2016;160:175-180.
28. Moisiadis VG, Matthews SG. Glucocorticoids and fetal programming part 2: mechanisms. Nat Rev Endocrinol. 2014;10:403-411.
29. Abe H, Hidaka N, Kawagoe C, Odagiri K, Watanabe Y, Ikeda T, Ishizuka Y, Hashiguchi H, Takeda R, Nishimori T, Ishida Y. Prenatal psychological stress causes higher emotionali-ty, depression-like behavior, and elevated ac-tivity in the hypothalamic-pituitary-adrenal axis. Neurosci Res. 2007;59:145-151.
30. Bosch O, Much W, Bredewold R, Slattery DA, Neumann ID. Prenatal stress increases HPA ax-is activity and impairs maternal care in lactat-ing female offspring: Implications for postpar-tum mood disorder. Psychoneuroendocrinol. 2007;32:267-278.
31. Brunton PJ, Russell JA. Prenatal social stress in the rat programmes neuroendocrine and be-havioral responses to stress in the adult off-spring: Sex-specific effects. J Neuroendocrinol. 2010;22:258-271.
32. Henry C, Kabbaj M, Simon H, Le Moal M, Maccari S. Prenatal stress increases the hypo-thalamic-pituitary-adrenal axis response in young and adult rats. J Neuroendocrinol. 1994;6:341-345.
33. Jafari Z, Mehla J, Kolb BE, Moharjerani MH. Prenatal noise stress impairs HPA axis and cognitive performance in mice. Scientific Rep. 2017;7:10560.
34. Mueller BR, Bale TL. Sex-specific programming of offspring emotionality after stress early in pregnancy. J Neurosci. 2008;28:9055-9065.
35. Sanchez MM, McCormack K, Grand AP, Fulks R, Graff A, Maestripieri D. Effects of sex and early maternal abuse on adrenocorticotropin hormone and cortisol responses to the cortico-tropin-releasing hormone challenge during the first 3 years of life in group-living rhesus mon-keys. Dev Psychopathol. 2010; 22:45-53.
36. Weinstock M, Matlina E, Maor GI, Rosen H, McEwen BS. Prenatal stress selectively alters the reactivity of the hypothalamic-pituitary adren-al system in the female rat. Brain Res. 1992; 595:195-200.
37. McLean MA, Simcock G, Elgbeili G, Laplante DP, Kildea S, Hurrion E, Lequertier B, Cobham VE, King S. Disaster-related prenatal maternal stress, and childhood HPA-axis regulation and anxiety: The QF2011 Queensland flood study. Psychoneuroendocrinol. 2020;118:104716.
38. Bosch OJ, Kromer SA, Neumann ID. Prenatal stress: opposite effects on anxiety and hypo-thalamic expression of vasopressin and corti-cotropin-releasing hormone in rats selectively bred for high and low anxiety. Eur J Neurosci. 2006;23:541-551.
39. Piviana SG, Rakitskaya VV, Akulova VK, Ordyan NE. Activity of the hypothalamic-pituitary-adrenal system in prenatally stress male rats on the experimental model of post-traumatic stress disorder. Bull Exper Biol Med. 2016;160:601-604.
40. Fan JM, Chen XQ, Jin H, Du JZ. Gestational hypoxia alone or combined with restraint sen-sitizes the hypothalamic-pituitary-adrenal axis and induces anxiety-like behavior in adult male rat offspring. Neurosci. 2009;159:1363-1373.
41. Jezova D, Skultetyova I, Makatsori A, Moncek F, Duncko R. Hypothalamic-pituitary-adrenocortical axis function and hedonic be-havior in adult male and female rats prenatal-ly stressed by maternal food restriction. Stress. 2002;5:177-183.
42. Wang X, Meng FS, Liu ZY, Fan JM, Hao K, Chen XQ, Du JZ. Gestational hypoxia induces sex-differential methylation of Crh1 linked to anxiety behavior. Mol Neurobiol. 2013;48:544-555.
43. Zohar I, Weinstock M. Differential effect of prenatal stress on the expression of corticotro-pin-releasing hormone and its receptors in the hypothalamus and amygdala of male and fe-male mice. J Neuroendocrinol. 2011;23:320-328.
44. Maccari S, Kruger HJ, Morley-Fletcher S, Szyf M, Brunton PJ. The consequences of early-life adversity: Neurobiological, behavioral and epigenetic adaptations. J Neuroendocrinol. 2014;26:707-723.
45. Lautarescu A, Craig MC, Glover V. Prenatal stress: Effects on fetal and child brain devel-opment. Int Rev Neurobiol. 2020;150:17-40.
46. Cottrell EC, Seckl JR. Prenatal stress, glucocor-ticoids and the programming of adult disease. Front Behav Neurosci. 2009; 3:article 19.
47. Barbazanges A, Piazza PV, Le Moal M, Mac-cari S. Maternal glucocorticoid secretion me-diates long-term effects of prenatal stress. J Neurosci. 1996;16:3943-3949.
48. McEwen BS. Stress and hippocampal plasticity. Ann Rev Neurosci. 1999;22:105-122.
49. Shoener JA, Baig R, Page KC. Prenatal expo-sure to dexamethasone alters hippocampal drive on hypothalamic-pituitary adrenal axis activity in adult male rats. Am J Physiol Regul Integr Comp Physiol. 2006;290:R1366-R1373.
50. Szuran T, Pliska V, Pokorny J, Welzl H. Prena-tal stress in rats: Effects on plasma corti-costerone, hippocampal glucocorticoid recep-tors, and maze performance. Physiol Behav. 2000;71:353-362.
51. Welberg LAM, Seckl JR, Holmes MC. Prenatal glucocorticoid programming of brain cortico-steroid receptors and corticotrophin-releasing hormone: Possible implications for behavior. Neurosci. 2001;104:71-79.
52. Pascuan CG, Di Rosso ME, Pivoz-Avedikian JE, Wald MR, Zorrilla Zubilete MA, Genaro AM. Alteration of neurotrophin and cytokine ex-pression in lymphocytes as novel markers of spatial memory deficits induced by prenatal stress. Physiol Behav. 2017;173:144-155.
53. Liao L, Yao X, Huang J, Bai S. Prenatal stress up-regulated hippocampal glucocorticoid re-ceptor expression in female adult rat off-spring. Int J Morphol. 202;36:400-405.
54. Ward HE, Johnson EA, Salm AK, Birkle DL. Ef-fects of prenatal stress on defensive with-drawal behavior and corticotropin releasing factor systems in rat brain. Physiol Behav. 2000;70:359-366.
55. Cratty MS, Ward HE, Johnson EA, Azzaro AJ, Birkle DL. Prenatal stress increases corticotro-pin-releasing factor (CRF) content and release from rat amygdala minces. Brain Res. 1995;675:297-302.
56. Bale TL. Epigenetic and transgenerational re-programming of brain development. Nat Rev Neurosci. 2015;16:332-344.
57. Glover V, O’Connor TG, O’Donnell K. Prenatal stress and the programming of the HPA axis. Neurosci Biobehav Rev. 2010;35:17-22.
58. Palma-Gudiel H, Cordova-Palomera A, Eix-arch E, Deuschle M, Fananas L. Maternal psy-chological stress during pregnancy alters the epigenetic signature of the glucocorticoid re-ceptor gene promotor in their offspring: a me-ta analysis. Epigenetics. 2015;10:893-902.
59. Hamada H, Matthews SG. Prenatal program-ming of stress responsiveness and behaviours: Progress and perspectives. J Neuroendocrinol. 2018;31:e12674.
60. McGowan PO, Matthews SG. Prenatal stress, glucocorticoids, and developmental program-ming of the stress response. Endocrinol. 2018;159:69-83.
61. Gray JD, Kogan JF, Marrocco J, McEwen BS. Genomic and epigenetic mechanisms of gluco-corticoids in the brain. Nature Rev Endocrinol. 2017;13:661-673.
62. McEwen BS. Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev. 2007;87:873-904.
63. Lv Y, Chen P, Kuang L, Han Z, Solanki B, Zhou W, Tao F, Chen R, Yao Y. Role of corticotro-pin-releasing hormone in the impact of chronic stress during pregnancy on inducing depres-sion in male offspring mice. Brain Res. 2020;1747:147029.
64. Grundwald NJ, Brunton PJ. Prenatal stress programs neuroendocrine stress responses and affective behaviors in second generation rats in a sex-dependent manner. Psychoneuroen-docrinol. 2015;62:204-216.
65. Mathey LIP. Neuroendocrinology of pregnan-cy: participation of sex hormones. In Marsh, C. (Ed.). (2021). Reproductive Hormones. IntechOpen. doi: 10.5772/intechopen.91499
66. Walley SN, Roepke TA. Perinatal exposure to endocrine disrupting compounds and the con-trol of feeding behavior-An overview. Horm Behav. 2018;101:22-28.
67. Martinez-Arguelles DB, Papadopoulos V. Mechanisms mediating environmental chemi-cal-induced endocrine disruption in the adren-al gland. Front Endocrinol. 2015;6:article 29.
68. MacKay H, Abizaid A. A plurality of molecular targets: The receptor ecosystem for bisphenol-A (BPA). Horm Behav. 2018;101:59-67.
69. Nesan D, Sewell LC, Kurrasch DM. Opening the black box of endocrine disruption of brain development: Lessons from the characteriza-tion of Bisphenol A. Horm Behav. 2018;101:50-58.
70. Panagiotidou E, Zerva S, Mitsiou DJ, Alexis MN, Kitraki E. Perinatal exposure to low-dose bisphenol A affects the neuroendocrine stress response in rats. J Endocrinol. 2014;220(3):207-218.
71. Poimenova A, Markaki E, Rahiotis C, Kitraki E. Corticosterone-regulated actions in the rat brain are affected by perinatal exposure to low dose of bisphenol A. Neurosci. 2010;167(3):741-749.
72. Zimmer KE, Gutleb AC, Lyche JL, Dahl E, Osham IC, Krogenaes A, Skaare JU, Ropstad E. Altered stress-induced cortisol levels in goats exposed to polychlorinated biphenyls (PCB 126 and PCB 153) during fetal and postnatal development. J Toxicol Environ Health A. 2009;72(3-4):164-172.
73. Reilly MP, Weeks CD, Topper VY, Thompson LM, Crews D, Gore AC. The effects of prenatal PCBs on adult social behavior in rats. Horm Behav. 2015;73:47-55.
74. Salgado-Freiria R, Lopez-Doval S, Lafuente A. Perfluorooctane sulfonate (PFOS) can alter the hypothalamic-pituitary-adrenal (HPA) axis ac-tivity by modifying CRF1 and glucocorticoid receptors. Tox Lett. 2018;295:1-9.
75. Harris EP, Allardice HA, Schenk AK, Rissman EF. Effects of maternal or paternal bisphenol A exposure on offspring behavior. Horm Behav. 2018;101:68-76.
76. Wiersielis KR, Samuels BA, Roepke TA. Perina-tal exposure to bisphenol A at the intersection of stress, anxiety and depression. Neurotox Teratol. 2020; 79:106884.
77. Sobolewski M, Conrad K, Marvin E, Allen JL, Cory-Slechta DA. Endocrine active metals, prenatal stress and enhanced neurobehavioral disruption. Horm Behav. 2018;101:36-49.
78. Jacobs MN, Marczylo EL, Guerrero-Bosagna C, Ruegg J. Marked for life: Effects of endo-crine disrupting chemicals. Ann Rev Environ Re-sour. 2017;42:105-160.
79. Streifer M, Core AC. Epigenetics, estrogenic endocrine-disrupting chemicals (EDCs) and the brain. Advan Pharmacol. 2021;92:73-99.
80. Van Cauwenbergh O, Di Serafino A, Tygat J, Soubry A. Transgenerational epigenetic ef-fects from male exposure to endocrine-disrupting compounds: a systematic review on research in mammals. Clin Epigenet. 2020;12:65
81. Anway MD, Skinner MK. Epigenetic transgen-erational actions of endocrine disruptors. En-docrionol. 2006;Suppl:S430S49.
82. Di Criscio M, Ekholm Lodahl J, Stamatakis A, Kitraki E, Bakoyiannis I, Repouskou A, Bornehag CG, Gennings C, Lupu D, Ruegg J. A human-relevant mixture of endocrine disrupt-ing chemicals induces changes in hippocampal DNA methylation correlating with hyperactive behavior in male mice. Chemosphere. 2023;313:137633.
83. Stein LJ, Gunier RB, Harley K, Kogut K, Brad-man A, Eskenazi B. Early childhood adversity potentiates the adverse association between prenatal organophosphate pesticide exposure and child IQ: The CHAMACOS cohort. Neuro-toxicol. 2016;56:180–7.
84. Huang J, Eskenazi B, Bornman R, Rauch S, Chevrier J. Maternal Peripartum Serum DDT/E and Urinary Pyrethroid Metabolite Concentra-tions and Child Infections at 2 Years in the VHEMBE Birth Cohort. Environ Health Perspect. 2018;126:067006.