Formation of human gonads in the early stages of fetal development
ANATOMY AND CELL BIOLOGY IN CLINICAL PRACTICE
Abstract
The development of gonads in human embryos is considered. Unlike other organs, gonads include not only somatic, but also germ cells. The specification of the latter begins in the human embryo during the first phase of gastrulation (12th–13thday of gestation), i.e. even before the formation of the germ layers. The cells of the germ line originate in the epiblast and the wall of the amniotic vesicle, from there they move into the wall of the yolk sac and then they migrate to the gonadal anlages — the genital ridges. The latter develop from the coelomic epithelium covering the medioventral surfaces of mesonephroses. After the migration is completed, the cells of germ line invade the gonads. Before the beginning of the 7thweek of gestation, the gonad of embryos of both sexes is morphologically identical and is called bipotential (indifferent), its further development depends on genetic sex. Morphological differentiation of the male gonad begins at week 7 due to the expression of theSRYgene, which is the trigger of the male signaling pathway. The onset of morphological differentiation of the female gonad is slightly delayed and is associated with the absence of the Y chromosome, and therefore theSRYgene. In the absence of a trigger of the male signaling pathway, the female signaling pathway is activated and the morphological features of the embryonic ovary are formed.The further fate of the germ cells depends on the influence of the surrounding somatic cells of the gonad. Thus, in the male gonad, the cells of germ line enter into mitotic arrest at the stage of spermatogony, and in female gonad, germ cells complete the stage of mitosis, enter the prophase of the first division of meiosis and then enter into meiotic arrest at the stage of diplotene prophase of meiosis I. The entry of primary oocytes into meiotic arrest correlates with the onset of formation of primordial follicles. The follicular epithelium of these follicles transports the main factor of meiotic arrest, cyclic AMP, through gap junctions towards the cytoplasm of oocytes.
References
1. С hen D., Sun N., Hou L., Kim R., Faith J., Aslanyan M. et al. Human primordial germ cells are specified from lineage-primed progenitors. Cell Reports. 2019;29(13):4568–4582. https://doi.org/10.1016/j.celrep.2019.11.083.
2. Kobayashi T., Surani M.A. On the origin of the human germline. Development. 2018;145(16):dev150433. https://doi.org/10.1242/dev.150433.
3. Hancock G.V., Wamaitha S.E., Peretz L., Clark A.T. Mammalian primordial germ cell specification. Development. 2021;148(6):dev189217. https://doi.org/10.1242/dev.189217.
4. Castillo-Venzor A., Penfold C.A., Morgan M.D., Tang W., Kobayashi T., Wong F. et al. Origin and segregation of the human germline. Life Science Alliance. 2023;6(8):e202201706. https://doi.org/10.26508/lsa.202201706.
5. Irie N., Weinberger L., Tang W.C., Kobayashi T., Viukov S., Manor Y.S. et al. SOX17 is a critical specifier of human primordial germ cell fate. Cell. 2015;160(1-2):253–268. https://doi.org/10.1016/j.cell.2014.12.013.
6. Kerr C.L., Cheng L. 2010. The Dazzle in germ cell differentiation. J Mol Cell Biol. 2010;2(1):26–29. https://doi.org/10.1093/jmcb/mjp041.
7. Кожухарь В.Г. Дифференцировка эпителия зачатков гонад у ранних эмбрионов человека. Архив анатомии, гистологии и эмбриологии. 1978;74(4):84–90.
8. Matsen L.S., Lutterodt M.C., Andersen E.W., Byskov A.G., Andersen C.Y. Germ cell numbers in human embryonic and fetal gonads during the first two trimesters of pregnancy: Analysis of six published studies. Hum Reprod. 2011;26(8):2140–2145. https://doi.org/10.1093/humrep/der149.
9. Кожухарь В.Г. О секреторной активности целомического эпителия эмбриональной гонады человека как факторе привлечения мигрирующих гоноцитов. Архив анатомии, гистологии и эмбриологии. 1980;78(4):79–85.
10. Кожухарь В.Г. Дифференцировка целомического эпителия зачатков гонад млекопитающих и птиц. Архив анатомии, гистологии и эмбриологии. 1979;76(1):69–80.
11. Carlson B.M. Human embryology and developmental biology. 5th ed. Elsevier saunders; 2014.
12. Sekido R., Lovell-Badge R. Sex determination involves synergistic action of SRY and SF1 on a specific Sox9 enhancer. Nature. 2008;453:930–934. https://doi.org/10.1038/nature06944.
13. Sekido R., Lovell-Badge R. Sex determination and SRY: down to a wink and a nudge? Trends Genet. 2009;25(1):19–29. https://doi.org/10.1016/j.tig.2008.10.008.
14. Jakob S., Lovell-Badge R. Sex determination and the control of Sox9 expression in mammals. FEBS J. 2011;278(7):1002–1009. https://doi.org/10.1111/j.1742-4658.2011.08029.x.
15. Knower K.C., Kelly S., Ludbrook L.M., Bagheri-Fam S., Sim H., Bernard P. et al. Failure of SOX9 regulation in 46XY disorders of sex development with SRY, SOX9 and SF1 mutations. PLo S One. 2011;6(3):e17751. https://doi.org/10.1371/journal.pone.0017751.
16. Lau Y.F., Li Y. The human and mouse sex-determining SRY genes repress the Rspo1/beta-catenin signaling. J Genet Genomics. 2009;36(4):193–202. https://doi.org/10.1016/S1673-8527(08)60107-1.
17. Кожухарь В.Г. SRY и SOX9 — главные факторы генетической детерминации пола у млекопитающих. Цитология. 2012;54(5):390–404.
18. Bhattacharya I., Dey S. Emerging concepts on Leydig cell development in fetal and adult testis. Front Endocrinol. 2023;13:1086276. https://doi.org/10.3389/fendo.2022.1086276.
19. Sadler T.W. Langmans Medical Embryology. 14th ed. Wolters Kluwer; 2019.
20. Кожухарь В.Г. Целомический эпителий гонад в период морфологической дифференцировки пола у зародышей человека. Архив анатомии, гистологии и эмбриологии. 1979;76(6):84–92.
21. Кожухарь В.Г. Судьба гоноцитов млекопитающих: оогенез или сперматогенез. Цитология. 2011;53(10):778–787. EDN: OFYKQP.
22. Кожухарь В.Г., Валькович Э.И. Ранняя дифференцировка поддерживающих клеток извитых семенных канальце у человека (ультраструктурные проявления). Архив анатомии, гистологии и эмбриологии. 1985;89(10):93–99.
23. Le Bouffant R., Guerquin M.J., Duquenne C., Frydman N., Coffigny H., Rouiller-Fabre V. et al. Meiosis initiation in the human ovary requires intrinsic retinoic acid synthesis. Hum Reprod. 2010;25(10):2579–2590. https://doi.org/10.1093/humrep/deq195.
24. Jones K.T. Turning it on and off: M-phase promoting factor during meiotic maturation and fertilization. Mol Hum Reprod. 2004;10(1):1–5. https://doi.org/10.1093/molehr/gah009.
This work is licensed under a Creative Commons Attribution 4.0 International License.
