2017, Number 1
<< Back Next >>
TIP Rev Esp Cienc Quim Biol 2017; 20 (1)
A consideration of the establishment of sex in mammals
Díaz-Hernández V, Merchant-Larios H
Language: Spanish
References: 58
Page: 27-39
PDF size: 442.10 Kb.
ABSTRACT
Establishment of sex in mammals occurs at the moment of fertilization, however, the determination and sexual
differentiation of the gonad is required in order to establish the sexual phenotype of the individual. Since the
discovery of the Sry gene as the testis-determining factor, progress has been made in understanding the
mechanisms that lead to testicular development and establishment of the male phenotype. Although the
female phenotype is acquired even in the absence of the gonad, differentiation and ovarian maturation are
required for the establishment of secondary sexual characteristics. This work aims to describe the mechanisms
involved in sexual determination of the gonad and integrate them with the histological aspects that contribute
to gonadal sex differentiation. Once the gonadal sex is established, molecular aspects involved in the
masculinization of the individual are addressed. Finally, a brief review of the pathological processes resulting
from the alteration of the establishment of sex in humans is undertaken.
REFERENCES
Jost, A., Price, D. & Edwards, R.G. Hormonal factors in the sex differentiation of the mammalian foetus. Philos. Trans. R. Sox. Lond. B Biol. Sci. 259, 119-130 (1970).
Rey, R., Josso, N. & Racine, C. (eds. L.J. De Groot, G. Chrousos, & K. Dunkan) (Endotext (Internet), 2016).
Harley, V.R. & Goodfellow, P.N. The biochemical role of SRY in sex determination. Mol. Reprod. Dev. 39, 184-193 (1994). DOI: 10.1002/mrd.1080390211.
Berta, P., Hawkins, J.R., Sinclair, A.H., Taylor, A., Griffiths, B.L., Goodfellow, P.N. & Fellous, M. Genetic evidence equating SRY and the testis-determining factor. Nature 348, 448-450 (1990). DOI: 10.1038/348448A0.
Sinclair, A.H., Berta, P., Palmer, M.S., Hawkins, J.R., Griffiths, B.L., Smith, M.J., Foster, J.W., Frischauf, A.M., Lovell-Badge, R. & Goodfellow, P.N. A gene from the human sex-determining region encodes a protein with homology to a conserved DNAbinding motif. Nature 346, 240-244 (1990).
Jager, R.J., Anvret, M., Hall, K. & Scherer, G. A human XY female with a frame shift mutation in the candidate testis-determining gene SRY. Nature 348, 452-454 (1990).
Koopman, P., Gubbay, J., Vivian, N. & Goodfellow, P. Male development of chromosomally female mice transgenic for Sry. Nature. 351,117-121 (1991).
Hanley, N.A., Hagan, D.M., Clement-Jones, M., Ballc, S.G., Strachan, T., Salas-Cortés, L., McElreavey, K., Lindsay, S., Robson, S., Bullen, P., Ostrer, H. & Wilson, D.I. SRY, SOX9, and DAX1 expression patterns during human sex determination and gonadal development. Mechanisms of Development 91,403- 407. (2000).
Sekido, R., Bar, I., Narvaéz, V., Penny, G. & Lovell-Badge, R. SOX9 is up-regulated by the transient expression of SRY specifically in Sertoli cell precursors. Developmental Biology 274, 271-279 (2004).
Sekido, R. & Lovell-Badge, R. Sex determination involves synergistic action of SRY and SF1 on a specific Sox9 enhancer. Nature 453, 930-934 (2008).
Wilhelm, D., Martinson, F., Bradford, S., Wilson, M.J, Combes, A.N., Beverdam, A., Bowles, J., Mizusaki, H. & Koppman, H. Sertoli differentiation is induced both cell-autonomously and through prostaglandin signaling during mammalian sex determination. Developmental Biology 287, 111-124 (2005).
Wagner, T., Wirth, J., Meyer, J., Zabel, B., Held, M., Zimmer, J., Pasantes, J., Bricarelli, F.D., Keutel, J., Hustert, E., Wolf, U., Tommerup, N., Schempp, W. & Scherer, G. Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9. Cell 79, 1111-1120 (1994) DOI.org/10.1016/0092-8674(94)90041-8.
Swain, A., Zanaria, E., Hacker, A., Lovell-Badge, R. & Camerino, G. Mouse Dax1 expression is consistent with a role in sex determination as well as in adrenal and hypothalamus function. Nat. Genet. 12, 404-409 (1996).
Zanaria, E., Muscatelli, F., Bardoni, B., Strom, T.M., Guioli, S., Guo, W., Lalli, E., Moser, C., Walker, A.P., McCabe, E.R., Meitinger, T., Monaco, A., Sassone-Corsi, P. & Camerino, G. An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita. Nature 372, 635-641 (1994).
Bardoni, B., Zanaria, E, Guioli, S., Floridia, G., Worley, K.C., Tonini, G, Ferrante, E., Chiumello, G., McCabe, E.R.B., Fraccaro, M., Zuffardi, O. & Carmerino, G. A dosage sensitive locus at chromosome Xp21 is involved in male to female sex reversal. Nat. Genet. 7, 497-501 (1994).
Muscatelli, F., Strom, T.M., Walker, A.P., Zanaria, E., Recan, D., Meindl, A., Bardoni, B., Guioli, S., Zehetner, G., Rabl, W., Schwarz, H.P., Kaplan, J.C. & Camerino, G. Mutations in the DAX- 1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism. Nature 372, 672-676 (1994).
Meeks, J.J., Weiss, J. & Jameson, J.L. Dax1 is required for testis determination. Nat. Genet. 34, 32-33 (2003)
Raffin-Sanson, M.L., Oudet, B., Salenave, S., Brailly-Tabard, S., Pehuet, M., Christin-Maitre, S., Morel, Y. & Young, J. A man with a DAX1/NR0B1 mutation, normal puberty, and an intact hypothalamic–pituitary–gonadal axis but deteriorating oligospermia during long-term follow-up. European Journal of Endocrinology168, K45-K50 (2013) DOI: 10.1530/eje-12-1055.
Mou, L., Xie, N., Yang, L., Liu, Y., Diao, R., Cai, Z., Li, H. & Gui, Y. A Novel Mutation of DAX-1 Associated with Secretory Azoospermia. PLoS ONE 10, e0133997 (2015) DOI: 10.1371/ journal.pone.0133997.
Ponikwicka-Tyszko, D., Kotula-Balak, M., Jarzabek, K., Bilinska, B. & Wolczynski, S. The DAX1 mutation in a patient with hypogonadotropic hypogonadism and adrenal hypoplasia congenita causes functional disruption of induction of spermatogenesis. Journal of Assisted Reproduction and Genetics 29,811-816 (2012). DOI: 10.1007/s10815-012-9778-y.
Ludbrook, L.M., Bernard, P., Bagheri-Fam, S., Ryan, J., Sekido, R., Wilhelm, D., Lovell-Badge, R. & Harley, V.R. Excess DAX1 leads to XY ovotesticular disorder of sex development (DSD) in mice by inhibiting steroidogenic factor-1 (SF1) activation of the testis enhancer of SRY-box-9 (Sox9). Endocrinology 153, 1948- 1958 (2012). Epub 2012/02/02. DOI: 10.1210/en.2011-1428
Svingen, T. & Koopman, P. Building the mammalian testis: origins, differentiation, and assembly of the component cell populations. Genes & Development. 27, 2409-2426 (2013). DOI: 10.1101/ gad.228080.113.
Windley, S.P. & Wilhelm, D. Signaling Pathways Involved in Mammalian Sex Determination and Gonad Development. Sexual Development. 9, 297-315 (2015).
Bendsen, E., Byskov, A.G., Laursen, S.B., Larsen, H.P., Andersen, C.Y. & Westergaard, L.G. Number of germ cells and somatic cells in human fetal testes during the first weeks after sex differentiation. Human Reproduction 18,13-18 (2003).
Magre, S. & Jost, A. The initial phases of testicular organogenesis in the rat. An electron microscopy study. Arch. Ant. Microsc. Morphol. Exp. 69, 297-318 (1980).
Brennan, J., Karl, J. & Capel, B. Divergent Vascular Mechanisms Downstream of Sry Establish the Arterial System in the XY Gonad. Developmental Biology 244, 418-428 (2002).
Coveney, D., Cool, J., Oliver, T. & Capel, B. Four-dimensional analysis of vascularization during primary development of an organ, the gonad. Proceedings of The National Academy of Sciences of the USA 105,7212-7217 (2008).
Codesal, J., Regadera, J., Nistal, M., Regadera-Sejas, J. & Paniagua, R. Involution of human fetal Leydig cells. An immunohistochemical, ultraestructural and quantitative study. Journal of Anatomy. 172, 103-114 (1990).
Feng, S., Ferlin, A., Truong, A., Bathgate, R., Wade, J.D., Corbett, S., Han, S., Tannour-Louet, M., Lamb, D.J., Foresta, C. & Agoulnik, A. INSL3/RXFP2 Signaling in Testicular Descent: Mice and Men. Annals of the New York Academy of Sciences 1160,197-204 (2009).
Karl, J. & Capel, B. Sertoli Cells of the Mouse Testis Originate from the Coelomic Epithelium. Developmental Biology 203, 323-333 (1998).
Merchant-Larios, H. & Moreno-Mendoza, N. Mesonephric Stromal Cells Differentiate into Leydig Cells in the Mouse Fetal Testis. Experimental Cell Research 244, 230-238 (1998).
DeFalco, T., Takahashi, S. & Capel, B. Two distinct origins for Leydig cell progenitors in the fetal testis. Developmental Biology. 352,14-26 (2011).
Zhang, L., Chen, M., Wen, Q., Li, Y., Wang, Y., Wang, Y., Qin, Y., Cui, X., Yang, L. & Huff, V. Reprogramming of Sertoli cells to fetal-like Leydig cells by Wt1 ablation. Proceedings of the National Academy of Sciences 112, 4003-4008 (2015).
Colvin, J.S., Green, R.P., Schmahl, J., Capel, B. & Ornitz, D.M. Male-to-female sex reversal in mice lacking fibroblast growth factor 9. Cell 104,875-889 (2001).
Clark, A.M., Garland, K.K. & Russell, L.D. Desert hedgehog (Dhh) gene is required in the mouse testis for formation of adult-type Leydig cells and normal development of peritubular cells and seminiferous tubules. Biology of Reproduction 63,1825-1838. (2000).
Yao, H.H., Whoriskey, W. & Capel, B. Desert Hedgehog/Patched 1 signaling specifies fetal Leydig cell fate in testis organogenesis. Genes & Development 16,1433-1440 (2002).
Pask, A. The Reproductive System. In: Wilhelm D, Bernard P, editors. Non-coding RNA and the Reproductive System 1-12. (Dordrecht: Springer Netherlands, 2016).
Eicher, E.M. & Washburn, L.L. Genetic control of primary sex determination in mice. Annual Review of Genetics 20, 327-360 (1986).
McElreavey, K., Vilain, E., Abbas, N., Herskowitz, I. & Fellous, M. A regulatory cascade hypothesis for mammalian sex determination: SRY represses a negative regulator of male development. Proceedings of The National Academy of Sciences of the USA 90, 3368-3372 (1993).
Parma, P., Radi, O., Vidal, V., Chaboissier, M.C., Dellambra, E., Valentini, S., Guerra, L., Schedl, A. & Camerino, G. R-spondin1 is essential in sex determination, skin differentiation and malignancy. Nature Genetics 38, 1304-1309 (2006).
Tomizuka, K., Horikoshi, K., Kitada, R., Sugawara, Y., Iba, Y., Kojima, A., Yoshitome, A., Yamawaki, K., Amagai, M., Inoue, A., Oshima, T. & Kakitani, M. R-spondin1 plays an essential role in ovarian development through positively regulating Wnt-4 signaling. Human Molecular Genetics 17,1278-1291 (2008).
Schmidt, D., Ovitt, C.E., Anlag, K., Fehsenfeld, S., Gredsted, L., Treier, A.C. & Treier, M. The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance. Development 131: 933-942 (2004).
Matson, C.K., Murphy, M.W., Sarver, A.L., Griswold, M.D., Bardwell, B.J. & Zarkower, D. DMRT1 prevents female reprogramming in the postnatal mammalian testis. Nature476,101- 104 (2011).
Uhlenhaut, N.H., Jakob, S., Anlag, K., Eisenberger, T., Sekido, R., Kress, J., Treier, A.C., Klugmann, C., Klasen, C., Holter, N.I., Riethmacher, D., Schütz, G., Cooney, A.J., Lovell-Badge, R. & Treier, M. Somatic Sex Reprogramming of Adult Ovaries to Testes by FOXL2 Ablation. Cell 39,1130-1142 (2009).
Yu, M., Wang, J., Liu, W., Qin, J., Zhou, Q., Wang, Y., Huang, H., Chen, W. & Ma, C. Effects of tamoxifen on the sex determination gene and the activation of sex reversal in the developing gonad of mice. Toxicology 321,89-95 (2014).
Couse, J.F., Hewitt, S.C., Bunch, D.O., Sar, M., Walker, V.R., Davis, B.J. & Korach, K.S. Postnatal Sex Reversal of the Ovaries in Mice Lacking Estrogen Receptors α and β. Science 286, 2328- 2331 (1999).
Nelson, S.M., Telfer, E.E. & Anderson, R.A. The ageing ovary and uterus: new biological insights. Human Reproduction Update 19, 67-83 (2013). DOI: 10.1093/humupd/dms043.
Chen, Y., Breen, K. & Pepling, M.E. Estrogen can signal through multiple pathways to regulate oocyte cyst breakdown and primordial follicle assembly in the neonatal mouse ovary. Journal of Endocrinology 202,407-417 (2009).
Merchant-Larios, H. & Chimal-Monroy, J. in Developments in Ultrastructures of Reproduction 55-63 (eds. P.M. Motta, & M. Malpighi, 1989).
Satoh, M. Histogenesis and organogenesis of the gonad in human embryos. Journal of Anatomy 177, 86-107 (1991).
Edson, M.A., Nagaraja, A.K. & Matzuk, M.M. The Mammalian Ovary from Genesis to Revelation. Endocrine Reviews30(6):624- 712 (2009). DOI: 10.1210/er.2009-0012.
Zuckerman, S. The number of oocytes in the mature ovary. Recent Progress in Homone Research. 6, 63-108 (1951).
Ozakpinar, O.B., Maurer, A.M. & Ozsavci, D. Ovarian stem cells: From basic to clinical applications. World Journal of Stem Cells 7,757-768 (2015) DOI: 10.4252/wjsc.v7.i4.757.
Zhang, H., Zheng, W., Shen, Y., Adhikari, D., Ueno, H. & Liu, K. Experimental evidence showing that no mitotically active female germline progenitors exist in postnatal mouse ovaries. Proceedings of the National Academy of Sciences of the United States of America 109,12580-12585 (2012) DOI: 10.1073/pnas.1206600109.
Koubova, J., Menke, D.B., Zhou, Q., Capel, B., Griswold, M.D. & Page, D.C. Retinoic acid regulates sex-specific timing of meiotic initiation in mice. Proceedings of the National Academy of Sciences of the United States of America103, 2474-2479 (2006) DOI: 10.1073/pnas.0510813103.
Bowles, J., Knight, D., Smith, C., Wilhelm, D., Richman, J., Mamiya, S., Yashiro K., Chawengsaksophak, K., Wilson, M.J., Rossant, J. & Hamada, H. & Koopman, P. Retinoid signaling determines germ cell fate in mice. Science 312, 596-600 (2006).
Culty, M. Gonocytes, from the Fifties to the Present: Is There a Reason to Change the Name? Biology of Reproduction 46, 1-6 (2013). DOI: 10.1095/biolreprod.113.110544.
Lee, P.A., Houk, C.P., Ahmed, S.F. & Hughes, I.A. International Consensus Conference on Intersex organized by the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology. Consensus Statement on Management of Intersex Disorders. International Consensus Conference on Intersex. Pediatrics 118, e488-e500 (2006). DOI: 10.1542/ peds.2006-0738.