Skip to main content

The Reproductive System

  • Chapter
Fetal and Neonatal Pathology

Development of the reproductive system, which comprises the gonads and external genitals in male and female embryos and fetuses, is under very complex and exquisitely synchronized genetic and hormonal control. The reproductive system is unique among the functional organ systems in the body in that it has the most pronounced sexual dimorphism. The gonads can develop either into a testis or an ovary, which differ markedly from each other in several aspects of the biology of gamete production. On the other hand, the accessory reproductive organs in the female are mainly geared for future implantations and gestations, while the male function is limited to the delivery of spermatozoa. During the last decades, a number of genes responsible for primary sex differentiation have been discovered, as well as endocrine and paracrine signaling pathways regulating these events and the subsequent development of gonads, ducts, and external genitalia. Many of the breakthroughs in our understanding of this system were made in observing abnormal development of the reproductive system in humans or in animal models with targeted gene disruption. Despite these advances, a great deal remains to be elucidated. While certain gene pathways leading to reproductive abnormalities have been relatively well described, little is known about the role of environmental and lifestyle factors, especially in mild cases. A possible relationship between prenatal exposures to environmental endocrine disrupters and abnormalities of the reproductive system, including genital malformations, testicular germ cell tumors, and some forms of infertility in adult life has been proposed (Toppari et al. 1996; Skakkebaek et al. 2001).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 419.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Barbaux S, Niaudet P, Gubler MC, et al. (1997) Donor splice-site mutations in WT1 are responsible for Frasier syndrome. Nat Genet 17:467–470.

    Article  PubMed  CAS  Google Scholar 

  • Bendsen E, Byskov AG, Andersen CY, Westergaard LG (2006) Number of germ cells and somatic cells in human fetal ovaries during the fi rst weeks after sex differentiation. Hum Reprod 21:30–35.

    Article  PubMed  CAS  Google Scholar 

  • Boisen KA, Kaleva K, Main KM, et al. (2004) Difference in the prevalence of cryptorchidism in infants between two Nordic countries. Lancet 363:1264–1269.

    Article  PubMed  CAS  Google Scholar 

  • Boisen KA, Chellakooty M, Schmidt IM, et al. (2005) Hypospadias in a cohort of 1072 Danish newborn boys: prevalence and relationship to placental weight, anthropometrical measurements at birth and reproductive hormone levels at 3 months of age. J Clin Endocrinol Metab 90:4041–4046.

    Article  PubMed  CAS  Google Scholar 

  • Capel B, Albrecht KH, Washburn LL, Eicher EM (1999) Migration of mesonephric cells into the mammalian gonad depends on Sry. Mech Dev 84:127–131.

    Article  PubMed  CAS  Google Scholar 

  • Chambers I, Colby D, Robertson M, et al. (2003) Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 113:643–655.

    Article  PubMed  CAS  Google Scholar 

  • Emmen JM, McLuskey A, Grootegoed JA, Brinkmann AO (1998) Androgen action during male sex differentiation includes suppression of cranial suspensory ligament development. Hum Reprod 13:1272–1280.

    Article  PubMed  CAS  Google Scholar 

  • Forest MG (2001) Diagnosis and treatment of disorders of sexual development. In: DeGroot LJ, Jameson JL (eds) Endocrinology, 4th ed. WB Saunders, Philadelphia, 2001, pp. 1974–2010.

    Google Scholar 

  • Goodfellow PN, Camerino G (1999) DAX-1, an “antit-estis” gene. Cell Mol Life Sci 55:857–863.

    PubMed  CAS  Google Scholar 

  • Hannema SE, Scott IS, Rajpert-De Meyts E, et al. (2006) Testicular development in the complete androgen insensitivity syndrome. J Pathol 208:518–527.

    Article  PubMed  CAS  Google Scholar 

  • Huang B, Wang S, Ning Y, et al. (1999) Autosomal XX sex reversal caused by duplication of SOX9. Am J Med Genet 87:349–353.

    Article  PubMed  CAS  Google Scholar 

  • Hutson JM, Hasthorpe S, Heyns CF (1997) Anatomical and functional aspects of testicular descent and cryptorchidism. Endocr Rev 18:259–280.

    Article  PubMed  CAS  Google Scholar 

  • Jackson MB, John Radcliffe Hospital Cryptorchidism Study Group (1988) The epidemiology of cryptorchi-dism. Horm Res 30:153–156.

    Article  PubMed  CAS  Google Scholar 

  • Kremer H, Kraaij R, Toledo SP, et al. (1995) Male pseu-dohermaphroditism due to a homozygous missense mutation of the luteinizing hormone receptor gene. Nat Genet 9:160–164.

    Article  PubMed  CAS  Google Scholar 

  • Lawson KA, Dunn NR, Roelen BAJ, et al. (1999) Bmp4 is required for the generation of primordial germ cells in the mouse embryo. Genes Dev 13:424–436.

    Article  PubMed  CAS  Google Scholar 

  • Molyneaux K, Wylie C (2004) Primordial germ cell migration. Int J Dev Biol 48:537–544.

    Article  PubMed  CAS  Google Scholar 

  • Nef S, Parada LF (1999) Cryptorchidism in mice mutant for Insl3. Nat Genet 22:295–299.

    Article  PubMed  CAS  Google Scholar 

  • Nielsen J, Wohlert M (1991) Sex chromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in Århus, Denmark. In: Evans JA, Hamerton JL, Robinson A (eds) Children and Young Adults with Sex Chromosome Aneuploidy. Wiley-Liss, New York, pp. 209–223.

    Google Scholar 

  • Ohinata Y, Payer B, O'Carroll D, et al. (2005) Blimp1 is a critical determinant of the germ cell lineage in mice. Nature 436:207–213.

    Article  PubMed  CAS  Google Scholar 

  • Quigley CA, De Bellis A, Marschke KB, et al. (1995) Androgen receptor defects: historical, clinical and molecular perspectives. Endocr Rev 16:271–321.

    PubMed  CAS  Google Scholar 

  • Rajpert-De Meyts E, Hanstein R, Jorgensen N, et al. (2004) Developmental expression of POU5F1 (OCT-3/4) in normal and dysgenetic human gonads. Hum Reprod 19:1338–1344.

    Article  PubMed  CAS  Google Scholar 

  • Rajpert-De Meyts E, Jorgensen NE, Graem N, et al. (1999) Expression of anti-müllerian hormone during normal and pathological gonadal development: association with differentiation of Sertoli and granulosa cells. J Clin Endocrinol Metab 84:3836–3844.

    Article  PubMed  Google Scholar 

  • Raymond CS, Murphy MW, O'Sullivan MG, et al. (2000) Dmrt1, a gene related to worm and fl y sexual regulators, is required for mammalian testis differentiation. Genes Dev 14:2587–2595.

    Article  PubMed  CAS  Google Scholar 

  • Saitou M, Barton SC, Surani MA. (2002) A molecular programme for the specifi cation of germ cell fate in mice. Nature 418:293–300.

    Article  PubMed  CAS  Google Scholar 

  • Satge D, Jacobsen GK, Cessot F, et al. (1996) A fetus with Down syndrome and intratubular germ cell neopla-sia. Pediatr Pathol Lab Med 16:107–112.

    Article  PubMed  CAS  Google Scholar 

  • Skakkebaek NE, Rajpert-De Meyts E, Main KM (2001) Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod 16:972–978.

    Article  PubMed  CAS  Google Scholar 

  • Swain A, Zanaria E, Hacker A, et al. (1996) Mouse Dax1 expression is consistent with a role in sex determination as well as in adrenal and hypothalamus function. Nat Genet 12:404–409.

    Article  PubMed  CAS  Google Scholar 

  • Toppari J, Kaleva M, Virtanen HE (2001) Trends in the incidence of cryptorchidism and hypospadias, and methodological limitations of registry-based data. Hum Reprod Update 7:282–286.

    Article  PubMed  CAS  Google Scholar 

  • Toppari J, Larsen JC, Christiansen P, et al. (1996) Male reproductive health and environmental chemicals with estrogenic effects. Environ Health Perspect 104(suppl 4):742–747.

    Google Scholar 

  • Vainio SJ, Itäranta PV, Peräsaari JP, et al. (1999) Wnts as kidney tubule inducing factors. Int J Dev Biol 43:419–423.

    PubMed  CAS  Google Scholar 

  • Virtanen HE, Kaleva M, Haavisto AM, et al. (2001) The birth rate of hypospadias in the Turku area in Finland. APMIS 109:96–100.

    Article  PubMed  CAS  Google Scholar 

  • Wikström AM, Raivio T, Hadziselimovic F, et al. (2004) Klinefelter syndrome in adolescence: onset of puberty is associated with accelerated germ cell depletion. J Clin Endocrinol Metab 89:2263–2270.

    Article  PubMed  Google Scholar 

  • Ying Y, Qi X, Zhao GQ (2001) Induction of primordial germ cells from murine epiblasts by synergistic action of BMP4 and BMP8B signaling pathways. Proc Natl Acad Sci USA 98:7858–7862.

    Article  PubMed  CAS  Google Scholar 

  • Ying Y, Zhao GQ (2001) Cooperation of endoderm-derived BMP2 end extraembryonic ectoderm-derived BMP4 in primordial germ cell generation in the mouse. Dev Biol 232:484–492.

    Article  PubMed  CAS  Google Scholar 

  • Zimmermann S, Steding G, Emmen JM, et al. (1999) Targeted disruption of the Insl3 gene causes bilateral cryptorchidism. Mol Endocrinol 13:681–691.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer-Verlag London Limited

About this chapter

Cite this chapter

Meyts, E.RD., Graem, N. (2007). The Reproductive System. In: Keeling, J.W., Khong, T.Y. (eds) Fetal and Neonatal Pathology. Springer, London. https://doi.org/10.1007/978-1-84628-743-5_23

Download citation

  • DOI: https://doi.org/10.1007/978-1-84628-743-5_23

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-84628-524-0

  • Online ISBN: 978-1-84628-743-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics