UNSW Embryology

Genital System - Male

© Dr Mark Hill (2008)

Acknowledgements

Introduction

This page introduces male gonad (testis) and reproductive tract development. The paired mesonephric ducts, also historically called Wolffian ducts, are preserved in male development and lost in females. The initial difference in male and female gonad development are dependent on testis-determining factor (TDF) the protein product of the Y chromosome SRY gene. Recent studies have indicated that additional factors may also be required for full differentiation. (More? See also Spermatogenesis | SRY)

Male Gonad (testis) Development (228 Kb)	Male External Genitalia (288 Kb)	Testes Descent (172 Kb)

(Clicking image or text will open movie, more movies can be seen on the Urogenital Movies page)

Page Links: Introduction | Some Recent Findings | Development Overview | Testicular Descent | Leydig Cells | Movies | References | Glossary

Other Pages: Y chromosome | Genital Abmormalities | Week 1 - Spermatogenesis | Endocrine Abnormalities | Endocrine Development - Pituitary

Some Recent Findings

Wilhelm D, Palmer S, Koopman P. Sex determination and gonadal development in mammals. Physiol Rev. 2007 Jan;87(1):1-28. Review.

"We review here the molecular and cellular events (differentiation, migration, proliferation, and communication) that distinguish testis and ovary during fetal development, and the changes in gene regulation that underpin these two alternate pathways."

Toppari J, Virtanen H, Skakkebaek NE, Main KM. Environmental effects on hormonal regulation of testicular descent. J Steroid Biochem Mol Biol. 2006 Dec;102(1-5):184-6. (More? Testicular Descent)

"Regulation of testicular descent is hormonally regulated, but the reasons for maldescent remain unknown in most cases."

Y Chromosome

The Y Chromosome contains approximately 200+ genes and consists of 50 million base pairs. Only 50% of its content has been determined. (More? Y chromosome)

Development Overview

Sex Determination

• Humans (week 5-6)
• Germ cells migrate into gonadal ridge
• Gonads (male/female) identical at this stage, Indifferent

Gonad development

• dependent on sex chromosome
• Y testes
• No Y ovary

SRY

• SRY protein (Testes determining factor, TDF) binds DNA
• Transcription factor, Bends DNA 70-80 degrees

Internal Genital Organs

• All embryos form paired
• Mesonephric duct, see kidney development
• Paramesonephric duct, Humans 7th week Invagination of coelomic epithelium Cord grows and terminates on urogenital sinus
• Male Gonad (testes) secretes Mullerian duct inhibitory factor (MDIF) which causes regression of paramesonephric duct
• Male Gonad (testes) secretes Testosterone which retains mesonephric duct

External Genital Organs

• All embryos initially same (indifferent)
• Testosterone differentiates male

Leydig Cells

Leydig cells named after german zoologist Franz von Leydig (1821 - 1908). These cells produce the male testicular androgens and occur during life prenatally fetal and postnatally at puberty.

Fetal Leydig Cells

Have a hormonal role in male genitalia differentiation and are lost postnatally. These cells arise approximately at 6 weeks (human) and 12.5 dpc (mouse) and there appears to be differences in hormonal sensitivity between the species. Their initial differentiation requires both luteinizing hormone (LH) and adrenocorticotrophic hormone (ACTH) and therefore normal pituitary development.

(More? Endocrine Development - Pituitary)

Adult (Puberty) Leydig Cells

Have a hormonal role in puberty, secondary sex characteristics and sexual maturation. Their initial differentiation from peritubular mesenchymal cells does not require gonadotropin, but development and function are dependent upon luteinizing hormone (LH). The cells differentiate with three discrete stages (newly formed, immature, mature) leading to a decrease in proliferation and increasing testosterone biosynthetic capacity. Insulin-like growth factor I (IGF-I) stimulates proliferation of immature cells and promotes their maturation. Testosterone and estrogen inhibit the process of precursor cell differentiation and may be responsible for the cessation of proliferation in the adult Leydig cells.

(More? Leydig reviews)

Links: Franz von Leydig

Peritubular Cells

Sertoli Cells

Puberty - immature Sertoli cells cease to proliferate and differentiate.

Molecular factors: Follicle Stimulating Hormone (FSH) -> Krüppel-like factor 4 (KLF4)

Krüppel-like factor 4 (KLF4) - zinc finger transcription factor, terminal differentiation of epithelial cells.

Epidermal Growth Factor (EGF)

Transforming Growth Factor-beta (TGFbeta)

Puberty

In humans at puberty, hormonal and morphological changes occur within the gonad and other systems (secondary sex characteristics). Within the testis the immature Sertoli cells cease to proliferate and differentiate. Spermatogonium proliferate and spermatogenesis begins, and it takes about 70 days for cells to mature from the diploid spermatogonium to a primary spermatocyte. This maturation occurs in waves along the seminiferous tubules.

Histology sections through the testis seminiferous tubule (Images: UWA Blue Histology)

(More? Week 1 - Spermatogenesis)

Male Genital Movies

More movies can be seen on the Urogenital Movies page.

Male Gonad (testis) Development (228 Kb)	Male External Genitalia (288 Kb)	Testes Descent (172 Kb)

(Clicking image or text will open movie)

Testicular Descent

This topic is also covered on Genital Abmormalities page.

Toppari J, Virtanen H, Skakkebaek NE, Main KM. Environmental effects on hormonal regulation of testicular descent. J Steroid Biochem Mol Biol. 2006 Dec;102(1-5):184-6.

"Regulation of testicular descent is hormonally regulated, but the reasons for maldescent remain unknown in most cases. The main regulatory hormones are Leydig cell-derived testosterone and insulin-like factor 3 (INSL3). Luteinizing hormone (LH) stimulates the secretion of these hormones, but the secretory responses to LH are different: INSL3 secretion increases slowly and may reflect the LH dependent differentiated status of Leydig cells, whereas testosterone response to LH is immediate. Testosterone contributes to the involution of the suspensory ligament and to the inguinoscrotal phase of the descent, while INSL3 acts mainly in transabdominal descent by stimulating the growth of the gubernaculum. INSL3 acts through a G-protein coupled receptor LGR8. "

Kaleva M, Toppari J. Cryptorchidism: an indicator of testicular dysgenesis? Cell Tissue Res. 2005 Oct;322(1):167-72.

"Cryptorchidism is a common ailment of new-born boys, affecting 1-9% of full term boys at birth."

References

Links: Reviews | Articles | Online Textbooks | Search Textbooks | Search PubMed | Glossary

PubMed

Reviews

• Baskin LS, Ebbers MB.    [See Related Articles] Hypospadias: anatomy, etiology, and technique. J Pediatr Surg. 2006 Mar;41(3):463-72.
• Kavlock R, Cummings A    [See Related Articles] Mode of action: inhibition of androgen receptor function--vinclozolin-induced malformations in reproductive development. Crit Rev Toxicol. 2005 Oct-Nov;35(8-9):721-6.
• Huhtaniemi I, Pelliniemi LJ. Fetal Leydig cells: cellular origin, morphology, life span, and special functional features. Proc Soc Exp Biol Med. 1992 Nov;201(2):125-40. Review.
• O'Shaughnessy PJ, Baker PJ, Johnston H. The foetal Leydig cell-- differentiation, function and regulation. Int J Androl. 2006 Feb;29(1):90-5; discussion 105-8. Review.
• Mendis-Handagama SM, Ariyaratne HB. Differentiation of the adult Leydig cell population in the postnatal testis. Biol Reprod. 2001 Sep;65(3):660-71. Review.

Articles

• Kelce WR, Monosson E, Gamcsik MP, Laws SC, Gray LE Jr.    [See Related Articles] Environmental hormone disruptors: evidence that vinclozolin developmental toxicity is mediated by antiandrogenic metabolites. Toxicol Appl Pharmacol. 1994 Jun;126(2):276-85.

Search PubMed

Search Feb 2007 "Testis Development" 10642 reference articles of which 990 were reviews.

Search PubMed: term = Testis Development | Wolffian Duct | Mesonephric Duct | Endocrine Disruptors |

Glossary of Terms

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Quick Links

Urogenital Pages:

Abnormalities | References | OMIM | Questions | Medline | Pig (stage13/14) | Human (Stage22) | Selected Human highpower
Text only page | WWW Links

Development Notes ----------------- Menstrual Cycle Week 1 Week 2 Week 3 Week 4 Placenta Serial Images Genes/DNA Molecular Dev Abnormal Dev Postnatal Dev Notes Index

System Notes ----------------- Heart/Cardiovascular Respiratory Coelomic cavity Gastrointestinal Tract Head and Neck Neural Neural Crest Eye Ear Nose Endocrine Urogenital Musculoskeletal Integumentary

Movies ----------------- Embryo Growth Ultrasound Week 1 Week 2 Week 3 Week 4 Stage 13/14 Stage 22 Neural Head and Neck Heart Vasculature Gastrointestinal Urogenital Other Embryos Larsen Internet

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