Human oocyte-like germ cells derived in vivo from testicular tissue of a Klinefelters’ patient: A case report
Main Article Content
Abstract
The combination of testicular biopsy and intracytoplasmic sperm injection procedures has assisted potentially azoospermic men with Klinefelters’ syndrome to have children. Approximately two-thirds of the time, a testicular sperm extraction procedure performed on a nonmosaic Klinefelter 47,XXY patient fails to isolate sperm. In the case report described herein, both wet preparation and histological examinations confirmed typical cellular morphologies associated with Klinefelter testicular tissue, including no spermatozoa. It did however, observe the unusual presence of oocyte-like cells representing a unique, theoretical in vivo transformation of pluripotent stem cells, probably spermatogonial, into primordial germ cells and gametes of the opposite sex, as previously documented only in the experimental mouse model.
Keywords:
testicular tissue, Klinefelter syndrome, oocytes, stem cells
Article Details
How to Cite
SCHIEWE, Mitchel C. et al.
Human oocyte-like germ cells derived in vivo from testicular tissue of a Klinefelters’ patient: A case report.
Medical Research Archives, [S.l.], v. 6, n. 2, feb. 2018.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/1704>. Date accessed: 26 dec. 2024.
doi: https://doi.org/10.18103/mra.v6i2.1704.
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. Aksglaede L, WikstrÖm AM, Rajpert-De Meyts E, Dunkel L, Skakkebaek NE, Juul A. Natural history of semiferous tubule degeneration in Klinefelter syndrome. Hum Reprod Update. 2006;12:39-48.
2. Tournaye H, Stassen C, Liebaers I, Van Assche E, Devroey P, Bonduelle M, Van Steirteghem A. Testicular sperm recovery in nine 47, XXY Klinefelter patients. Hum Reprod. 1996; 11:1644-1649.
3. Lue Y, Rao PN, Sinha Hikim AP, Im M, Salameh WA, Yen PH, Wang C, Swerdoff RS. XXY male mice: an experimental model for Klinefelter syndrome. Endocrinology. 2001; 142(4):1461-1470. doi: 10.1210/endo.142.4.8086.
4. Wistuba J, Luetjens CM, Stukenborg JB, Poplinski A, Werler S, Dittmann M, Damm OS, Hamalainen T, Simoni M, Gromoll J. Male 41, XXY* mice as a model for Klinefelter syndrome: hyperactivation of leydig cells. Endocrinology. 2010; 151(6): 2898-2910. doi: 10.1210/en.2009-1396.
5. Friedler S, Raziel A, Strassburger D, Schachter M, Bern O, Ron-El R. Outcome of ICSI using fresh and cryopreserved-thawed testicular spermatozoa in patients with non-mosaic Klinefelter’s syndrome. Hum Reprod. 2001; 16(12):2616-2620.
6. Seo JT, Park YS, Lee JS. Successful testicular sperm extraction in Korean Klinefelter syndrome. Urology. 2004; 64(6):1208-11. doi: 10.1016/j.urology.2004.07.013.
7. Okada H, Goda K, Yamamoto Y, Sofikitis N, Miyagawa I, Mio Y, Koshida M, Horie S. Age as a limiting factor for successful sperm retrieval in patients with nonmosaic Klinefelter’s syndrome. Fertil Steril. 2005a; 84(6):1662-64. doi: 10.1016/ j.fertnstert.2005. 05.053.
8. Selice R, Di Mambro A, Garolla A, Ficarra V, Iafrate M, Ferlin A, Foresta C. Spermatogenesis in Klinefelter syndrome. J Endocrinol Invest. 2011; 33(11):789-93. doi: 10.3275/6935.
9. Ron-el R, Freidler S, Strassburger D, Komarovsky D, Schachter M, Raziel A. Birth of a healthy neonate following the intracytoplasmic injection of testicular spermatozoa from a patient with Klinefelter’s syndrome. Hum Reprod. 1999; 14(2):368-70.
10. Okada H, Goda K, Muto S, Maruyama O, Koshida M, Horie S. Four pregnancies in nonmosaic Klinefelter’s syndrome using cryopreserved-thawed testicular sperm. Fertil Steril. 2005b; 84(6):1662-64. doi: 10.1016/j.fertnstert.2005.05.033.
11. Kyono K, Uto H, Nakajo Y, Kumagai S, Araki Y, Kanto S. Seven pregnancies and deliveries from non-mosaic Klinefelter syndrome patients using fresh and frozen testicular sperm. J Assist Reprod Genet. 2007; 24:47-51.
12. Greco E, Scarselli F, Minasi MG, Casciani V, Zavaglia D, Dente D, Tesarik J, Franco G. Birth of 16 healthy children after ICSI in cases of nonmosaic Klinefelter syndrome. Hum Reprod. 2013; 28(5):1155-1160. doi:10.1093/humrep/det046
13. Slepko N, Griparic L, Vargas V, Burgee K, Patel A, Santa Cruz P, Anderson R, Schiewe M, Gonzalez R, Silva F. A putative mesenchymal stem cells population isolated from adult human testes. Biochem Biophys Res Commun. 2009; 385:570-75. doi: 10.1016/j.bbrc.2009.05.103.
14. Koopman P, Munsterberg A, Capel B, Vivian N, Lovell-Badge R. Expression of a candidate sex-determining gene during mouse testis differentiation. Nature. 1990; 348 (6300):450-452. doi: 10.1038/348450a0
15. Conrad S, Renninger M, Hennenlotter J, Wiesner T, Just L, Bonin M, Aicher W, Buhring HJ, Mattheus U, Mack A, Wagner HJ, Minger S, Matzkies M, Reppel M, Hescheler J, Sievert KD, Stenzl A, Skutella T. Generation of pluripotent stem cells from adult human testis. Nature. 2008; 456(7220):344-349. doi: 10.1038/ nature07404
16. Golestaneh N, Kokkinaki M, Pant D, Jiang J, DeStefano D, Fernandez-Bueno C, Rone JD, Haddad BR, Gallicano GI, Dym M. Pluripotent stem cells derived from adult human testes. Stem Cells Dev. 2009; 18(8):1115-1126. doi: 10.1089/ scd.2008.0347
17. Guan K, Nayernia K, Maier LS, Wagner S, Dressel R, Lee JH, Nolte J, Wolf F, Li M, Engel W, Hasenfuss G. Pluripotency of spermatogonial stem cells from adult mouse testis. Nature. 2006; 440(7088):1199-1203. doi: 10.1038/nature04697
18. Kanatsu-Shinohara M, Inoue K, Lee J, Yoshimoto M, Ogonuki N, Miki H, Baba S, Kato T, Kazuki Y, Toyokuni S, Toyoshima M, Niwa O, Oshimura M, Heike T, Nakahata T, Ishino F, Ogura A, Shinohara T. Generation of pluripotent stem cells from neonatal mouse testis. Cell. 2004; 119(7):1001-1012. doi: 10.1016/ j.cell.2004.11.011
19. Kossack N, Meneses J, Shefi S, Nguyen HN, Chavez S, Nicholas C, Gromoll J, Turek PJ, Reijo-Pera RA. Isolation and characterization of pluripotent human spermatogonial stem cell-derived cells. Stem Cells. 2009; 27(1): 138-149. doi: 10.1634/stemcells.2008-0439
20. Izadyar F, Wong J, Maki C, Pacchiarotti J, Ramos T, Howerton K, Yuen C, Greilach S, Zhao HH, Chow M, Chow Y-C, Rao J, Barritt J, Bar-Chama N, Cooperman A. Identification and characterization of repopulating spermatogonial stem cells from the adult human testis. Hum Reprod. 2011; 26:1296–1306 doi: 10.1093/ humrep/der026
21. Schiewe MC, Rothman C, Spitz A, Werthman PE, Zeitlin SI, Anderson RE. Validation-verification of a highly effective, practical human testicular tissue in vitro culture -cryopreservation procedure aimed at optimizing pre-freeze and post-thaw motility. J Asst Reprod Genet. 2016; 33:519-28. doi: 10.1007/s10815-016-0659-7.
22. Eppig JJ, O'Brien MJ. Development in vitro of mouse oocytes from primordial follicles. Biol Reprod. 1996; 54(1):197-207. doi: 10.1095/biolreprod54.1.197
23. Hübner K, Fuhrmann G, Christenson LK, Kehler J, Reinbold R, De La Fuente R, Wood J, Strauss JF, Boiani M, Schöler HR. Derivation of oocytes from mouse embryonic stem cells. Science. 2003; 300:1251–1256. doi: 10.1126/science.1083452
24. Toyooka Y, Tsunekawa N, Akasu R, Noce T. Embryonic stem cells can form germ cells in vitro. Proc Natl Acad Sci USA. 2003; 100:11457–11462.
25. Wang L, Cao J, Ji P, Zhang D, Ma L, Dym M, Yu Z, Feng L. Oocyte-like cells induced from mouse spermatogonial stem cells. Cell & Bioscience. 2012; 2:27. doi: 10.1186/2045-3701-2-27
26. Martinez-Arroyo AM, Medrano JV, Remohi J, Simon C. Germ line development: lessons learned from pluripotent stem cells. Curr Opin Genet Dev. 2014; 28:64–70.
27. Hayashi K, Saitou M. Generation of eggs from mouse embryonic stem cells and induced pluripotent stem cells. Nat Protoc. 2013; 8(8):1513-1524. doi: 10.1038/nprot.2013.090
28. Hayashi K, Ogushi S, Kurimoto K, Shimamoto S, Ohta H, Saitou M. Offspring from oocytes derived from in vitro primordial derm cell-like cells in mice. Science. 2012; 338:971-975. doi: 10.1126/science.1226889
29. Mathews DJH, Donovan PJ, Harris J, Lovell-Badge R, Savulescu J, Faden R. Pluripotent stem cell-derived gametes: truth and (potential) consequences. Cell Stem Cell. 2009; 5(1):11-14. doi: 10.1016/stem.2009.06.005
30. Moreno, I., Miguez-Forjan, J.M., Simon, C., 2015. Artificial gametes from stem cells. Clin. Exp. Reprod. Med. 42(2):33-44. doi: 10.5653/cerm.2015.42.2.33
31. Smitz JE, Gilchrist RB. Are human oocytes from stem cells next? Nature Biotechnol. 2016; 34:1247-1248. doi:10.1038/nbt.3742
2. Tournaye H, Stassen C, Liebaers I, Van Assche E, Devroey P, Bonduelle M, Van Steirteghem A. Testicular sperm recovery in nine 47, XXY Klinefelter patients. Hum Reprod. 1996; 11:1644-1649.
3. Lue Y, Rao PN, Sinha Hikim AP, Im M, Salameh WA, Yen PH, Wang C, Swerdoff RS. XXY male mice: an experimental model for Klinefelter syndrome. Endocrinology. 2001; 142(4):1461-1470. doi: 10.1210/endo.142.4.8086.
4. Wistuba J, Luetjens CM, Stukenborg JB, Poplinski A, Werler S, Dittmann M, Damm OS, Hamalainen T, Simoni M, Gromoll J. Male 41, XXY* mice as a model for Klinefelter syndrome: hyperactivation of leydig cells. Endocrinology. 2010; 151(6): 2898-2910. doi: 10.1210/en.2009-1396.
5. Friedler S, Raziel A, Strassburger D, Schachter M, Bern O, Ron-El R. Outcome of ICSI using fresh and cryopreserved-thawed testicular spermatozoa in patients with non-mosaic Klinefelter’s syndrome. Hum Reprod. 2001; 16(12):2616-2620.
6. Seo JT, Park YS, Lee JS. Successful testicular sperm extraction in Korean Klinefelter syndrome. Urology. 2004; 64(6):1208-11. doi: 10.1016/j.urology.2004.07.013.
7. Okada H, Goda K, Yamamoto Y, Sofikitis N, Miyagawa I, Mio Y, Koshida M, Horie S. Age as a limiting factor for successful sperm retrieval in patients with nonmosaic Klinefelter’s syndrome. Fertil Steril. 2005a; 84(6):1662-64. doi: 10.1016/ j.fertnstert.2005. 05.053.
8. Selice R, Di Mambro A, Garolla A, Ficarra V, Iafrate M, Ferlin A, Foresta C. Spermatogenesis in Klinefelter syndrome. J Endocrinol Invest. 2011; 33(11):789-93. doi: 10.3275/6935.
9. Ron-el R, Freidler S, Strassburger D, Komarovsky D, Schachter M, Raziel A. Birth of a healthy neonate following the intracytoplasmic injection of testicular spermatozoa from a patient with Klinefelter’s syndrome. Hum Reprod. 1999; 14(2):368-70.
10. Okada H, Goda K, Muto S, Maruyama O, Koshida M, Horie S. Four pregnancies in nonmosaic Klinefelter’s syndrome using cryopreserved-thawed testicular sperm. Fertil Steril. 2005b; 84(6):1662-64. doi: 10.1016/j.fertnstert.2005.05.033.
11. Kyono K, Uto H, Nakajo Y, Kumagai S, Araki Y, Kanto S. Seven pregnancies and deliveries from non-mosaic Klinefelter syndrome patients using fresh and frozen testicular sperm. J Assist Reprod Genet. 2007; 24:47-51.
12. Greco E, Scarselli F, Minasi MG, Casciani V, Zavaglia D, Dente D, Tesarik J, Franco G. Birth of 16 healthy children after ICSI in cases of nonmosaic Klinefelter syndrome. Hum Reprod. 2013; 28(5):1155-1160. doi:10.1093/humrep/det046
13. Slepko N, Griparic L, Vargas V, Burgee K, Patel A, Santa Cruz P, Anderson R, Schiewe M, Gonzalez R, Silva F. A putative mesenchymal stem cells population isolated from adult human testes. Biochem Biophys Res Commun. 2009; 385:570-75. doi: 10.1016/j.bbrc.2009.05.103.
14. Koopman P, Munsterberg A, Capel B, Vivian N, Lovell-Badge R. Expression of a candidate sex-determining gene during mouse testis differentiation. Nature. 1990; 348 (6300):450-452. doi: 10.1038/348450a0
15. Conrad S, Renninger M, Hennenlotter J, Wiesner T, Just L, Bonin M, Aicher W, Buhring HJ, Mattheus U, Mack A, Wagner HJ, Minger S, Matzkies M, Reppel M, Hescheler J, Sievert KD, Stenzl A, Skutella T. Generation of pluripotent stem cells from adult human testis. Nature. 2008; 456(7220):344-349. doi: 10.1038/ nature07404
16. Golestaneh N, Kokkinaki M, Pant D, Jiang J, DeStefano D, Fernandez-Bueno C, Rone JD, Haddad BR, Gallicano GI, Dym M. Pluripotent stem cells derived from adult human testes. Stem Cells Dev. 2009; 18(8):1115-1126. doi: 10.1089/ scd.2008.0347
17. Guan K, Nayernia K, Maier LS, Wagner S, Dressel R, Lee JH, Nolte J, Wolf F, Li M, Engel W, Hasenfuss G. Pluripotency of spermatogonial stem cells from adult mouse testis. Nature. 2006; 440(7088):1199-1203. doi: 10.1038/nature04697
18. Kanatsu-Shinohara M, Inoue K, Lee J, Yoshimoto M, Ogonuki N, Miki H, Baba S, Kato T, Kazuki Y, Toyokuni S, Toyoshima M, Niwa O, Oshimura M, Heike T, Nakahata T, Ishino F, Ogura A, Shinohara T. Generation of pluripotent stem cells from neonatal mouse testis. Cell. 2004; 119(7):1001-1012. doi: 10.1016/ j.cell.2004.11.011
19. Kossack N, Meneses J, Shefi S, Nguyen HN, Chavez S, Nicholas C, Gromoll J, Turek PJ, Reijo-Pera RA. Isolation and characterization of pluripotent human spermatogonial stem cell-derived cells. Stem Cells. 2009; 27(1): 138-149. doi: 10.1634/stemcells.2008-0439
20. Izadyar F, Wong J, Maki C, Pacchiarotti J, Ramos T, Howerton K, Yuen C, Greilach S, Zhao HH, Chow M, Chow Y-C, Rao J, Barritt J, Bar-Chama N, Cooperman A. Identification and characterization of repopulating spermatogonial stem cells from the adult human testis. Hum Reprod. 2011; 26:1296–1306 doi: 10.1093/ humrep/der026
21. Schiewe MC, Rothman C, Spitz A, Werthman PE, Zeitlin SI, Anderson RE. Validation-verification of a highly effective, practical human testicular tissue in vitro culture -cryopreservation procedure aimed at optimizing pre-freeze and post-thaw motility. J Asst Reprod Genet. 2016; 33:519-28. doi: 10.1007/s10815-016-0659-7.
22. Eppig JJ, O'Brien MJ. Development in vitro of mouse oocytes from primordial follicles. Biol Reprod. 1996; 54(1):197-207. doi: 10.1095/biolreprod54.1.197
23. Hübner K, Fuhrmann G, Christenson LK, Kehler J, Reinbold R, De La Fuente R, Wood J, Strauss JF, Boiani M, Schöler HR. Derivation of oocytes from mouse embryonic stem cells. Science. 2003; 300:1251–1256. doi: 10.1126/science.1083452
24. Toyooka Y, Tsunekawa N, Akasu R, Noce T. Embryonic stem cells can form germ cells in vitro. Proc Natl Acad Sci USA. 2003; 100:11457–11462.
25. Wang L, Cao J, Ji P, Zhang D, Ma L, Dym M, Yu Z, Feng L. Oocyte-like cells induced from mouse spermatogonial stem cells. Cell & Bioscience. 2012; 2:27. doi: 10.1186/2045-3701-2-27
26. Martinez-Arroyo AM, Medrano JV, Remohi J, Simon C. Germ line development: lessons learned from pluripotent stem cells. Curr Opin Genet Dev. 2014; 28:64–70.
27. Hayashi K, Saitou M. Generation of eggs from mouse embryonic stem cells and induced pluripotent stem cells. Nat Protoc. 2013; 8(8):1513-1524. doi: 10.1038/nprot.2013.090
28. Hayashi K, Ogushi S, Kurimoto K, Shimamoto S, Ohta H, Saitou M. Offspring from oocytes derived from in vitro primordial derm cell-like cells in mice. Science. 2012; 338:971-975. doi: 10.1126/science.1226889
29. Mathews DJH, Donovan PJ, Harris J, Lovell-Badge R, Savulescu J, Faden R. Pluripotent stem cell-derived gametes: truth and (potential) consequences. Cell Stem Cell. 2009; 5(1):11-14. doi: 10.1016/stem.2009.06.005
30. Moreno, I., Miguez-Forjan, J.M., Simon, C., 2015. Artificial gametes from stem cells. Clin. Exp. Reprod. Med. 42(2):33-44. doi: 10.5653/cerm.2015.42.2.33
31. Smitz JE, Gilchrist RB. Are human oocytes from stem cells next? Nature Biotechnol. 2016; 34:1247-1248. doi:10.1038/nbt.3742