Abstract
Correct sexual development is arguably the most important trait in an organism’s life history since it is directly related to its genetic fitness. The developing gonad houses the germ cells, the only legacy we pass on to subsequent generations. Given the pivotal importance of correct reproductive function, it is confounding that disorders of sex development (DSDs) are among the most common congenital abnormalities in humans (Lee et al. J Pediatr Urol 8(6):611–615, 2012). Urogenital development is a highly complex process involving coordinated interactions between molecular and hormonal pathways in a tightly regulated order. The controls that regulate some of the key events in this process are beginning to be unraveled. This chapter provides an overview of our understanding of urogenital development from the gonads to the urogenital ducts and external genitalia.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Adriaenssens E, Lottin S, Dugimont T, Fauquette W, Coll J, Dupouy JP, Boilly B, Curgy JJ (1999) Steroid hormones modulate H19 gene expression in both mammary gland and uterus. Oncogene 18(31):4460–4473. doi:10.1038/sj.onc.1202819
Allgeier SH, Lin TM, Moore RW, Vezina CM, Abler LL, Peterson RE (2010) Androgenic regulation of ventral epithelial bud number and pattern in mouse urogenital sinus. Dev Dyn 239(2):373–385. doi:10.1002/dvdy.22169
Angiolini E, Fowden A, Coan P, Sandovici I, Smith P, Dean W, Burton G, Tycko B, Reik W, Sibley C, Constancia M (2006) Regulation of placental efficiency for nutrient transport by imprinted genes. Placenta 27(Suppl A):S98–S102, doi:S0143-4004(06)00003-8 [pii]
Barrionuevo F, Bagheri-Fam S, Klattig J, Kist R, Taketo MM, Englert C, Scherer G (2006) Homozygous inactivation of Sox9 causes complete XY sex reversal in mice. Biol Reprod 74(1):195–201
Behringer RR (1994) The in vivo roles of mullerian-inhibiting substance. Curr Top Dev Biol 29:171–187
Behringer RR, Finegold MJ, Cate RL (1994) Mullerian-inhibiting substance function during mammalian sexual development. Cell 79(3):415–425, doi:0092-8674(94)90251-8 [pii]
Bishop CE, Whitworth DJ, Qin Y, Agoulnik AI, Agoulnik IU, Harrison WR, Behringer RR, Overbeek PA (2000) A transgenic insertion upstream of sox9 is associated with dominant XX sex reversal in the mouse. Nat Genet 26(4):490–494
Borum K (1961) Oogenesis in the mouse. A study of the meiotic prophase. Exp Cell Res 24:495–507
Bowles J, Knight D, Smith C, Wilhelm D, Richman J, Mamiya S, Yashiro K, Chawengsaksophak K, Wilson MJ, Rossant J, Hamada H, Koopman P (2006) Retinoid signaling determines germ cell fate in mice. Science 312(5773):596–600, doi:1125691 [pii]
Brennan J, Capel B (2004) One tissue, two fates: molecular genetic events that underlie testis versus ovary development. Nat Rev Genet 5(7):509–521. doi:10.1038/nrg1381
Britt KL, Kerr J, O’Donnell L, Jones ME, Drummond AE, Davis SR, Simpson ER, Findlay JK (2002) Estrogen regulates development of the somatic cell phenotype in the eutherian ovary. FASEB J 16(11):1389–1397. doi:10.1096/fj.01-0992com
Britt KL, Saunders PK, McPherson SJ, Misso ML, Simpson ER, Findlay JK (2004) Estrogen actions on follicle formation and early follicle development. Biol Reprod 71(5):1712–1723. doi:10.1095/biolreprod.104.028175
Bullejos M, Bowles J, Koopman P (2002) Extensive vascularization of developing mouse ovaries revealed by caveolin-1 expression. Dev Dyn 225(1):95–99. doi:10.1002/dvdy.10128
Burgoyne PS, Buehr M, McLaren A (1988) XY follicle cells in ovaries of XX – XY female mouse chimaeras. Development 104(4):683–688
Capel B, Albrecht KH, Washburn LL, Eicher EM (1999) Migration of mesonephric cells into the mammalian gonad depends on Sry. Mech Dev 84(1–2):127–131
Cohn MJ (2004) Developmental genetics of the external genitalia. Adv Exp Med Biol 545:149–157
Couse JF, Hewitt SC, Bunch DO, Sar M, Walker VR, Davis BJ, Korach KS (1999) Postnatal sex reversal of the ovaries in mice lacking estrogen receptors alpha and beta. Science 286(5448):2328–2331, doi:8111 [pii]
Coveney D, Cool J, Oliver T, Capel B (2008) Four-dimensional analysis of vascularization during primary development of an organ, the gonad. Proc Natl Acad Sci U S A 105(20):7212–7217, doi:0707674105 [pii]
Daniel CW, Smith GH (1999) The mammary gland: a model for development. J Mammary Gland Biol Neoplasia 4(1):3–8
Du H, Taylor HS (2004) Molecular regulation of mullerian development by Hox genes. Ann N Y Acad Sci 1034:152–165, doi:1034/1/152 [pii]
Frojdman K, Paranko J, Kuopio T, Pelliniemi LJ (1989) Structural proteins in sexual differentiation of embryonic gonads. Int J Dev Biol 33(1):99–103
Gubbay J, Collignon J, Koopman P, Capel B, Economou A, Munsterberg A, Vivian N, Goodfellow P, Lovell-Badge R (1990) A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes. Nature 346(6281):245–250. doi:10.1038/346245a0
Hannema SE, Hughes IA (2007) Regulation of Wolffian duct development. Horm Res 67(3):142–151, doi:96644 [pii]
Harry JL, Koopman P, Brennan FE, Graves JA, Renfree MB (1995) Widespread expression of the testis-determining gene SRY in a marsupial. Nat Genet 11(3):347–349. doi:10.1038/ng1195-347
Hashimoto N, Kubokawa R, Yamazaki K, Noguchi M, Kato Y (1990) Germ cell deficiency causes testis cord differentiation in reconstituted mouse fetal ovaries. J Exp Zool 253(1):61–70. doi:10.1002/jez.1402530109
Henkes LE, Davis JS, Rueda BR (2003) Mutant mouse models and their contribution to our knowledge of corpus luteum development, function and regression. Reprod Biol Endocrinol 1:87. doi:10.1186/1477-7827-1-87
Hennighausen L, Robinson GW (2005) Information networks in the mammary gland. Nat Rev Mol Cell Biol 6(9):715–725. doi:10.1038/nrm1714
Hens JR, Wysolmerski JJ (2005) Key stages of mammary gland development: molecular mechanisms involved in the formation of the embryonic mammary gland. Breast Cancer Res 7(5):220–224, doi:bcr1306 [pii]
Hubertus J, Lacher M, Rottenkolber M, Muller-Hocker J, Berger M, Stehr M, von Schweinitz D, Kappler R (2011) Altered expression of imprinted genes in Wilms tumors. Oncol Rep 25(3):817–823. doi:10.3892/or.2010.1113
Josso N (1970a) Action of human testis on rat fetus Muller’s duct in organ culture. C R Acad Sci Hebd Seances Acad Sci D 271(23):2149–2152
Josso N (1970b) Action of testosterone on the Wolffian duct of rat fetus in organ culture. Arch Anat Microsc Morphol Exp 59(1):37–49
Ju X, Li Z, Zhang C, Qin C, Shao P, Li J, Li P, Cao Q, Zhang W, Wang Z, Yin C (2013) Clinical aspects and molecular genetics of persistent mullerian duct syndrome associated with transverse testicular ectopia: report of three cases. Urol Int 90(1):83–86, doi:000339599 [pii]
Kanai Y, Hayashi Y, Kawakami H, Takata K, Kurohmaru M, Hirano H, Nishida T (1991) Effect of tunicamycin, an inhibitor of protein glycosylation, on testicular cord organization in fetal mouse gonadal explants in vitro. Anat Rec 230(2):199–208. doi:10.1002/ar.1092300207
Kanai Y, Kawakami H, Takata K, Kurohmaru M, Hirano H, Hayashi Y (1992) Involvement of actin filaments in mouse testicular cord organization in vivo and in vitro. Biol Reprod 46(2):233–245
Katoh-Fukui Y, Tsuchiya R, Shiroishi T, Nakahara Y, Hashimoto N, Noguchi K, Higashinakagawa T (1998) Male-to-female sex reversal in M33 mutant mice. Nature 393(6686):688–692. doi:10.1038/31482
Keil KP, Mehta V, Abler LL, Joshi PS, Schmitz CT, Vezina CM (2012) Visualization and quantification of mouse prostate development by in situ hybridization. Differentiation 84(3):232–239, doi:S0301-4681(12)00106-5 [pii]
Kleinman HK, Weeks BS, Schnaper HW, Kibbey MC, Yamamura K, Grant DS (1993) The laminins: a family of basement membrane glycoproteins important in cell differentiation and tumor metastases. Vitam Horm 47:162–186
Kobayashi A, Stewart CA, Wang Y, Fujioka K, Thomas NC, Jamin SP, Behringer RR (2011) beta-Catenin is essential for Mullerian duct regression during male sexual differentiation. Development 138(10):1967–1975, doi:dev.056143 [pii]
Koopman P, Munsterberg A, Capel B, Vivian N, Lovell-Badge R (1990) Expression of a candidate sex-determining gene during mouse testis differentiation. Nature 348(6300):450–452
Koopman P, Gubbay J, Vivian N, Goodfellow P, Lovell-Badge R (1991) Male development of chromosomally female mice transgenic for Sry. Nature 351(6322):117–121. doi:10.1038/351117a0
Koubova J, Menke DB, Zhou Q, Capel B, Griswold MD, Page DC (2006) Retinoic acid regulates sex-specific timing of meiotic initiation in mice. Proc Natl Acad Sci U S A 103(8):2474–2479, doi:0510813103 [pii]
Kreidberg JA, Sariola H, Loring JM, Maeda M, Pelletier J, Housman D, Jaenisch R (1993) WT-1 is required for early kidney development. Cell 74(4):679–691, doi:0092-8674(93)90515-R [pii]
Kuroki S, Matoba S, Akiyoshi M, Matsumura Y, Miyachi H, Mise N, Abe K, Ogura A, Wilhelm D, Koopman P, Nozaki M, Kanai Y, Shinkai Y, Tachibana M (2013) Epigenetic regulation of mouse sex determination by the histone demethylase Jmjd1a. Science 341(6150):1106–1109, doi:341/6150/1106 [pii]
Lee P, Schober J, Nordenstrom A, Hoebeke P, Houk C, Looijenga L, Manzoni G, Reiner W, Woodhouse C (2012) Review of recent outcome data of disorders of sex development (DSD): emphasis on surgical and sexual outcomes. J Pediatr Urol 8(6):611–615, doi:S1477-5131(12)00253-7 [pii]
Lovell-Badge R, Robertson E (1990) XY female mice resulting from a heritable mutation in the primary testis-determining gene, Tdy. Development 109(3):635–646
Luo X, Ikeda Y, Parker KL (1994) A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation. Cell 77(4):481–490, doi:0092-8674(94)90211-9 [pii]
Magoffin DA (2005) Ovarian theca cell. Int J Biochem Cell Biol 37(7):1344–1349, doi:S1357-2725(05)00057-9 [pii]
Malki S, Berta P, Poulat F, Boizet-Bonhoure B (2005) Cytoplasmic retention of the sex-determining factor SOX9 via the microtubule network. Exp Cell Res 309(2):468–475, doi:S0014-4827(05)00326-5 [pii]
Martineau J, Nordqvist K, Tilmann C, Lovell-Badge R, Capel B (1997) Male-specific cell migration into the developing gonad. Curr Biol 7(12):958–968, doi:S0960-9822(06)00415-5 [pii]
Merchant H (1975) Rat gonadal and ovarioan organogenesis with and without germ cells. An ultrastructural study. Dev Biol 44(1):1–21
Merchant-Larios H, Moreno-Mendoza N, Buehr M (1993) The role of the mesonephros in cell differentiation and morphogenesis of the mouse fetal testis. Int J Dev Biol 37(3):407–415
Morita Y, Manganaro TF, Tao XJ, Martimbeau S, Donahoe PK, Tilly JL (1999) Requirement for phosphatidylinositol-3′-kinase in cytokine-mediated germ cell survival during fetal oogenesis in the mouse. Endocrinology 140(2):941–949
Palmer SJ, Burgoyne PS (1991) In situ analysis of fetal, prepuberal and adult XX – XY chimaeric mouse testes: Sertoli cells are predominantly, but not exclusively, XY. Development 112(1):265–268
Pask AJ, Calatayud NE, Shaw G, Wood WM, Renfree MB (2010) Oestrogen blocks the nuclear entry of SOX9 in the developing gonad of a marsupial mammal. BMC Biol 8(1):113, doi:1741-7007-8-113 [pii]
Paulsson M (1992) Basement membrane proteins: structure, assembly, and cellular interactions. Crit Rev Biochem Mol Biol 27(1–2):93–127. doi:10.3109/10409239209082560
Payne AH, Hardy MP, Russell LD (1996) The Leydig cell. Cache River Press, Vienna
Pelliniemi LJ, Frojdman K (2001) Structural and regulatory macromolecules in sex differentiation of gonads. J Exp Zool 290(5):523–528. doi:10.1002/jez.1096
Perriton CL, Powles N, Chiang C, Maconochie MK, Cohn MJ (2002) Sonic hedgehog signaling from the urethral epithelium controls external genital development. Dev Biol 247(1):26–46. doi:10.1006/dbio.2002.0668
Qin Y, Bishop CE (2005) Sox9 is sufficient for functional testis development producing fertile male mice in the absence of Sry. Hum Mol Genet 14(9):1221–1229
Qin Y, Kong LK, Poirier C, Truong C, Overbeek PA, Bishop CE (2004) Long-range activation of Sox9 in Odd Sex (Ods) mice. Hum Mol Genet 13(12):1213–1218. doi:10.1093/hmg/ddh141
Renfree MB, Ager EI, Shaw G, Pask AJ (2008) Genomic imprinting in marsupial placentation. Reproduction 136(5):523–531, doi:REP-08-0264 [pii]
Renfree MB, Suzuki S, Kaneko-Ishino T (2013) The origin and evolution of genomic imprinting and viviparity in mammals. Philos Trans R Soc Lond B Biol Sci 368(1609):20120151, doi:rstb.2012.0151 [pii]
Richardson LL, Kleinman HK, Dym M (1995) Basement membrane gene expression by Sertoli and peritubular myoid cells in vitro in the rat. Biol Reprod 52(2):320–330
Rossi P, Dolci S, Albanesi C, Grimaldi P, Geremia R (1993) Direct evidence that the mouse sex-determining gene Sry is expressed in the somatic cells of male fetal gonads and in the germ cell line in the adult testis. Mol Reprod Dev 34(4):369–373
Schmahl J, Capel B (2003) Cell proliferation is necessary for the determination of male fate in the gonad. Dev Biol 258(2):264–276
Schmahl J, Eicher EM, Washburn LL, Capel B (2000) Sry induces cell proliferation in the mouse gonad. Development 127(1):65–73
Sekido R, Lovell-Badge R (2008) Sex determination involves synergistic action of SRY and SF1 on a specific Sox9 enhancer. Nature 453(7197):930–934, doi:nature06944 [pii]
Shinoda K, Lei H, Yoshii H, Nomura M, Nagano M, Shiba H, Sasaki H, Osawa Y, Ninomiya Y, Niwa O et al (1995) Developmental defects of the ventromedial hypothalamic nucleus and pituitary gonadotroph in the Ftz-F1 disrupted mice. Dev Dyn 204(1):22–29. doi:10.1002/aja.1002040104
Siegel PM, Muller WJ (2010) Transcription factor regulatory networks in mammary epithelial development and tumorigenesis. Oncogene 29(19):2753–2759, doi:onc201043 [pii]
Stringer JM, Suzuki S, Pask AJ, Shaw G, Renfree MB (2012a) Promoter-specific expression and imprint status of marsupial IGF2. PLoS One 7(7):e41690. doi:10.1371/journal.pone.0041690
Stringer JM, Suzuki S, Pask AJ, Shaw G, Renfree MB (2012b) Selected imprinting of INS in the marsupial. Epigenetics Chromatin 5(1):14, doi:1756-8935-5-14 [pii]
Svingen T, Koopman P (2007) Involvement of homeobox genes in mammalian sexual development. Sex Dev 1(1):12–23, doi:96235 [pii]
Timpl R (1993) Proteoglycans of basement membranes. Experientia 49(5):417–428
Tung PS, Fritz IB (1993) Interactions of Sertoli cells with laminin are essential to maintain integrity of the cytoskeleton and barrier functions of cells in culture in the two-chambered assembly. J Cell Physiol 156(1):1–11. doi:10.1002/jcp.1041560102
Tyndale-Biscoe CH, Renfree MB (1987) Reproductive physiology of marsupials, Monographs on marsupial biology. Cambridge University Press, Cambridge/New York
Vidal VP, Chaboissier MC, de Rooij DG, Schedl A (2001) Sox9 induces testis development in XX transgenic mice. Nat Genet 28(3):216–217
Wilhelm D, Martinson F, Bradford S, Wilson MJ, Combes AN, Beverdam A, Bowles J, Mizusaki H, Koopman P (2005) Sertoli cell differentiation is induced both cell-autonomously and through prostaglandin signaling during mammalian sex determination. Dev Biol 287(1):111–124
Wilhelm D, Palmer S, Koopman P (2007) Sex determination and gonadal development in mammals. Physiol Rev 87(1):1–28. doi:10.1152/physrev.00009.2006, 87/1/1 [pii]
Yamada G (2005) Reproductive/urogenital organ development and molecular genetic cascades: glamorous developmental processes of bodies. J Biochem 137(6):665–669. doi:10.1093/jb/mvi085, 137/6/665 [pii]
Yamada G, Suzuki K, Haraguchi R, Miyagawa S, Satoh Y, Kamimura M, Nakagata N, Kataoka H, Kuroiwa A, Chen Y (2006) Molecular genetic cascades for external genitalia formation: an emerging organogenesis program. Dev Dyn 235(7):1738–1752. doi:10.1002/dvdy.20807
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Pask, A. (2016). The Reproductive System. In: Wilhelm, D., Bernard, P. (eds) Non-coding RNA and the Reproductive System. Advances in Experimental Medicine and Biology, vol 886. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-7417-8_1
Download citation
DOI: https://doi.org/10.1007/978-94-017-7417-8_1
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-017-7415-4
Online ISBN: 978-94-017-7417-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)