Genital - Male Development
|Embryology - 23 Oct 2018 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Textbooks
- 4 Movies
- 5 Development Overview
- 6 Gonad - Testis
- 7 Internal Genital
- 8 External Genital
- 9 Hormones
- 10 Additional Images
- 11 References
- 12 Terms
- 13 Glossary Links
The male and female reproductive systems develop initially "indifferently", it is the product of the Y chromosome SRY gene that makes the "difference". The mesonephric duct (Wolffian Duct) contributes the majority of male internal genital tract.
Embryonic gonad development leads to the mesonephric/paramesonephric duct changes, while the external genitaila remain indeterminate in appearance through to the fetal period.
Importantly its sex chromosome dependence, late embryonic/fetal differential development, complex morphogenic changes, long time-course, hormonal sensitivity and hormonal influences make it a system prone to many different abnormalities.
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Murat Ulu, Nükhet Kütük, Muhammet Furkan Cıcık, Suheyb Bilge, Hüseyin Akçay, Suna Saygılı, Mehmet İbrahim Tuğlu, Alper Alkan Effects of boric acid on bone formation after maxillary sinus floor augmentation in rabbits. Oral Maxillofac Surg: 2018; PubMed 30345483
Min-Bo Zang, Qiao Zhou, Yun-Fei Zhu, Ming-Xi Liu, Zuo-Min Zhou Effects of chemotherapeutic agent bendamustine for non-hodgkin lymphoma on spermatogenesis in mice. J Biomed Res: 2018; PubMed 30333280
Chen Qian, Zhongluan Wu, Roy Chun-Laam Ng, Maria-Mercè Garcia-Barceló, Zheng-Wei Yuan, Kenneth Kak Yuen Wong, Paul Kwong Hang Tam, Vincent Chi Hang Lui Conditional deletion of platelet derived growth factor receptor alpha (Pdgfra) in urorectal mesenchyme causes mesenchyme apoptosis and urorectal developmental anomalies in mice. Cell Death Differ.: 2018; PubMed 30323271
Małgorzata M Dobrzyńska, Aneta Gajowik, Ewa A Jankowska-Steifer, Joanna Radzikowska, Ewa J Tyrkiel Reproductive and developmental F1 toxicity following exposure of pubescent F0 male mice to bisphenol A alone and in a combination with X-rays irradiation. Toxicology: 2018; PubMed 30321649
Mai M Hasan, Sally M Shalaby, Jehan El-Gendy, Eman M A Abdelghany Beneficial effects of metformin on muscle atrophy induced by obesity in rats. J. Cell. Biochem.: 2018; PubMed 30320911
- Human Embryology (2nd ed.) Larson Chapter 10 p261-306
- The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Chapter 13 p303-346
- Before We Are Born (5th ed.) Moore and Persaud Chapter 14 p289-326
- Essentials of Human Embryology, Larson Chapter 10 p173-205
- Human Embryology, Fitzgerald and Fitzgerald Chapter 21-22 p134-152
- Developmental Biology (6th ed.) Gilbert Chapter 14 Intermediate Mesoderm
|Mouse Primordial Germ Cell Migration|
Three main stages during development, mesonephric/paramesonephric duct changes are one of the first male/female differences that occur in development, while external genitaila remain indeterminate in appearance for quite a while.
- Differentiation of gonad (Sex determination)
- Differentiation of internal genital organs
- Differentiation of external genital organs
The 2nd and 3rd stages dependent on endocrine gonad. Reproductive development has a long maturation timecourse, begining in the embryo and finishing in puberty. (More? Puberty Development)
Historic Images of Genital Changes
|Urogenital indifferent||Urogenital male||Urogenital female|
Gonad - Testis
See the detailed notes on testis development.
- Links: Testis Development
Mesonephric duct or Wolffian duct differentiates to form the male internal genital tract the vas deferens (ductus deferens, vas deferens or simply vas). Associated with the duct are the male prostate and accessory glands.
|Human Mesonephric Duct position (week 6 to 11)|
| Schematic representations of the descent of the mesonephric duct (Wolffian duct, WD) or vas deferens. Anterior view.
|Adult Ductus deferens|
|Human prostate histology||Corpora Amylacea||Submucosal gland|
|(adult, low power overview)||(adult, detail)||(adult, high power detail)|
- external genitalia are initially identical and undergo male and female differentiation under the influence or absence of steroidal sex hormones.
- Indifferent stage ‐ cloaca divided by proliferating mesenchyme forming the urorectal septum which separates the ventral urogenital sinus from the dorsal rectum.
- Difference stage ‐ locally in this region the presence or absence of dihydrotestosterone (DHT), generated from testosterone, determines male/female development.
Anti-Müllerian Hormone (AMH, Müllerian Inhibiting Substance, MIS, Müllerian Inhibiting Factor, MIF) is a secreted glycoprotein factor of the transforming growth factor-beta, TGF-beta superfamily, that regulates gonadal and genital tract development. (Gene locus 19p13.3)
In the male embryo, the Sertoli cell secrete AMH and inhibit paramesonephric (Mullerian) duct development. This secreted hormone also acts to differentiate the Leydig cells (interstitial cells).
Ligand of TGF-beta (transforming growth factor-beta) superfamily and receptor binds to the anti-Mullerian hormone receptor type 2. Signalling pathway activate SMAD family transcription factors that regulate gene expression.
In postnatal males, AMH increases during the first month, reaching peak level at 6 months of age, and then slowly declines during childhood falling to low levels in puberty.
In reproductive age women, AMH is produced in the ovary by the granulosa cells surrounding preantral and small antral follicles and serum levels may reflect the remaining follicle cohort and decrease with age.
Sertoli cells release mainly a prohormone (proAMH), that is cleaved by subtilisin/kexin-type proprotein convertases or serine proteinases. The cleaved protein forms a stable complex (AMHN,C). Therefore the circulating AMH is a mixture of proAMH and AMHN,C. It has been suggested that proAMH may be activated within the gonads and also by its endocrine target-cells.
Preproprotein proteolytically processed to generate N- and C-terminal cleavage products, that homodimerize and associate to form a biologically active noncovalent complex. (see Protein Atlas)
Male testosterone and AMH levels
During ovary follicle development, the granulosa cells secrete AMH and it may have a role in follicular recruitment and development. and may also function in postnatal elevation of FSH secretion in females.
Other AMH Tissues
- The placenta has also been shown to both synthesise AMH and express its receptors.
- AMH receptors have been identified in both the pituitary and brain.
| Male presence of Dihydrotestosterone (DHT, 5α-dihydrotestosterone, androstanolone, 5α-androstan-17β-ol-3-one).
Androgen and Digit ratio (2D:4D)
The ratio of 2nd and 4th finger (D, digit) length. This ratio has been suggested to relate to high fetal testosterone concentration (males have lower 2D:4D than females) and has been shown for several species. Although a study in mice has not shown the same correlation. There have been some suggestions that the ratio may also be an indicator of various neurological abnormalities.
To measure (2D:4D) - using your right hand palm up, measure the index finger (2) and ring finger (4) length from palm to tip. Dividing the index finger by the ring finger gives the 2D:4D ratio, average women ratio is 1, average men is 0.98.
- Ortega EA, Salvador Q, Fernandez M & Ward MA. (2018). Alterations of sex determination pathway in the genital ridges of males with limited Y chromosome genes. Biol. Reprod. , , . PMID: 30285093 DOI.
- Gredler ML, Seifert AW & Cohn MJ. (2015). Tissue-specific roles of Fgfr2 in development of the external genitalia. Development , 142, 2203-12. PMID: 26081573 DOI.
- Ishiguro T, Tamagawa S & Ogawa H. (1992). [Changes of pupil size in brain death patients]. Seishin Shinkeigaku Zasshi , 94, 864-73. PMID: 1484906
- Funke S, Flach E, Kiss I, Sándor J, Vida G, Bódis J & Ertl T. (2010). Male reproductive tract abnormalities: more common after assisted reproduction?. Early Hum. Dev. , 86, 547-50. PMID: 20674196 DOI.
- Lin C, Yin Y, Veith GM, Fisher AV, Long F & Ma L. (2009). Temporal and spatial dissection of Shh signaling in genital tubercle development. Development , 136, 3959-67. PMID: 19906863 DOI.
- Wu X, Ferrara C, Shapiro E & Grishina I. (2009). Bmp7 expression and null phenotype in the urogenital system suggest a role in re-organization of the urethral epithelium. Gene Expr. Patterns , 9, 224-30. PMID: 19159697 DOI.
- Jin ZW, Abe H, Hinata N, Li XW, Murakami G & Rodríguez-Vázquez JF. (2016). Descent of mesonephric duct to the final position of the vas deferens in human embryo and fetus. Anat Cell Biol , 49, 231-240. PMID: 28127497 DOI.
- Pang K, Ryan JF, Baxevanis AD & Martindale MQ. (2011). Evolution of the TGF-β signaling pathway and its potential role in the ctenophore, Mnemiopsis leidyi. PLoS ONE , 6, e24152. PMID: 21931657 DOI.
- McLennan IS & Pankhurst MW. (2015). Anti-Müllerian hormone is a gonadal cytokine with two circulating forms and cryptic actions. J. Endocrinol. , 226, R45-57. PMID: 26163524 DOI.
- Garrel G, Racine C, L'Hôte D, Denoyelle C, Guigon CJ, di Clemente N & Cohen-Tannoudji J. (2016). Anti-Müllerian hormone: a new actor of sexual dimorphism in pituitary gonadotrope activity before puberty. Sci Rep , 6, 23790. PMID: 27030385 DOI.
- Novembri R, Funghi L, Voltolini C, Belmonte G, Vannuccini S, Torricelli M & Petraglia F. (2015). Placenta expresses anti-Müllerian hormone and its receptor: Sex-related difference in fetal membranes. Placenta , 36, 731-7. PMID: 25972076 DOI.
- McIntyre MH. (2006). The use of digit ratios as markers for perinatal androgen action. Reprod. Biol. Endocrinol. , 4, 10. PMID: 16504142 DOI.
- Yan RH, Bunning M, Wahlsten D & Hurd PL. (2009). Digit ratio (2Dratio4D) differences between 20 strains of inbred mice. PLoS ONE , 4, e5801. PMID: 19495421 DOI.
Koopman P. (2010). The delicate balance between male and female sex determining pathways: potential for disruption of early steps in sexual development. Int. J. Androl. , 33, 252-8. PMID: 19845801 DOI.
Adham IM, Emmen JM & Engel W. (2000). The role of the testicular factor INSL3 in establishing the gonadal position. Mol. Cell. Endocrinol. , 160, 11-6. PMID: 10715534
Hiort O & Holterhus PM. (2000). The molecular basis of male sexual differentiation. Eur. J. Endocrinol. , 142, 101-10. PMID: 10664515
Chawengsaksophak K, Svingen T, Ng ET, Epp T, Spiller CM, Clark C, Cooper H & Koopman P. (2012). Loss of Wnt5a disrupts primordial germ cell migration and male sexual development in mice. Biol. Reprod. , 86, 1-12. PMID: 21900680 DOI.
Cools M, Wolffenbuttel KP, Drop SL, Oosterhuis JW & Looijenga LH. (2011). Gonadal development and tumor formation at the crossroads of male and female sex determination. Sex Dev , 5, 167-80. PMID: 21791949 DOI.
- mesonephric duct - (Wollfian duct) An early developing urogenital paired duct system that initially runs the length of the embryo, that will differentiate and form the male reproductive duct system (ductus deferens). In females, this duct degenerates occasionally some remnants may remain associated in broad ligament.
- Wolffian duct - (mesonephric duct, preferred terminology), A developmental duct that runs from the mesonephros to cloaca. The duct in male differentiates to form the ductus deferens and in female the same structure regresses. Historically named after Caspar Friedrich Wolff (1733-1794), a German scientist and early embryology researcher and is said to have established the doctrine of germ layers. (More? Caspar Friedrich Wolff)
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Cite this page: Hill, M.A. (2018, October 23) Embryology Genital - Male Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Genital_-_Male_Development
- © Dr Mark Hill 2018, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G