Talk:Genital - Male Development
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Cite this page: Hill, M.A. (2019, September 19) Embryology Genital - Male Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Genital_-_Male_Development
Alternative (backdoor) androgen production and masculinization in the human fetus
PLoS Biol. 2019 Feb 14;17(2):e3000002. doi: 10.1371/journal.pbio.3000002. eCollection 2019 Feb.
O'Shaughnessy PJ1, Antignac JP2, Le Bizec B2, Morvan ML2, Svechnikov K3, Söder O3, Savchuk I3, Monteiro A1, Soffientini U1, Johnston ZC1, Bellingham M1, Hough D1, Walker N4, Filis P4, Fowler PA4.
Abstract Masculinization of the external genitalia in humans is dependent on formation of 5α-dihydrotestosterone (DHT) through both the canonical androgenic pathway and an alternative (backdoor) pathway. The fetal testes are essential for canonical androgen production, but little is known about the synthesis of backdoor androgens, despite their known critical role in masculinization. In this study, we have measured plasma and tissue levels of endogenous steroids in second trimester human fetuses using multidimensional and high-resolution mass spectrometry. Results show that androsterone is the principal backdoor androgen in the male fetal circulation and that DHT is undetectable (<1 ng/mL), while in female fetuses, there are significantly lower levels of androsterone and testosterone. In the male, intermediates in the backdoor pathway are found primarily in the placenta and fetal liver, with significant androsterone levels also in the fetal adrenal. Backdoor intermediates, including androsterone, are only present at very low levels in the fetal testes. This is consistent with transcript levels of enzymes involved in the alternate pathway (steroid 5α-reductase type 1 [SRD5A1], aldo-keto reductase type 1C2 [AKR1C2], aldo-keto reductase type 1C4 [AKR1C4], cytochrome P450 17A1 [CYP17A1]), as measured by quantitative PCR (qPCR). These data identify androsterone as the predominant backdoor androgen in the human fetus and show that circulating levels are sex dependent, but also that there is little de novo synthesis in the testis. Instead, the data indicate that placental progesterone acts as substrate for synthesis of backdoor androgens, which occurs across several tissues. Masculinization of the human fetus depends, therefore, on testosterone and androsterone synthesis by both the fetal testes and nongonadal tissues, leading to DHT formation at the genital tubercle. Our findings also provide a solid basis to explain why placental insufficiency is associated with disorders of sex development in humans. PMID: 30763313 PMCID: PMC6375548 DOI: 10.1371/journal.pbio.3000002
Tissue-specific roles of Fgfr2 in development of the external genitalia
Development. 2015 Jun 15;142(12):2203-12. doi: 10.1242/dev.119891.
Gredler ML1, Seifert AW1, Cohn MJ2.
Congenital anomalies frequently occur in organs that undergo tubulogenesis. Hypospadias is a urethral tube defect defined by mislocalized, oversized, or multiple openings of the penile urethra. Deletion of Fgfr2 or its ligand Fgf10 results in severe hypospadias in mice, in which the entire urethral plate is open along the ventral side of the penis. In the genital tubercle, the embryonic precursor of the penis and clitoris, Fgfr2 is expressed in two epithelial populations: the endodermally derived urethral epithelium and the ectodermally derived surface epithelium. Here, we investigate the tissue-specific roles of Fgfr2 in external genital development by generating conditional deletions of Fgfr2 in each of these cell types. Conditional deletion of Fgfr2 results in two distinct phenotypes: endodermal Fgfr2 deletion causes mild hypospadias and inhibits maturation of a complex urethral epithelium, whereas loss of ectodermal Fgfr2 results in severe hypospadias and absence of the ventral prepuce. Although these cell type-specific mutants exhibit distinctive genital anomalies, cellular analysis reveals that Fgfr2 regulates epithelial maturation and cell cycle progression in the urethral endoderm and in the surface ectoderm. The unexpected finding that ectodermal deletion of Fgfr2 results in the most severe hypospadias highlights a major role for Fgfr2 in the developing genital surface epithelium, where epithelial maturation is required for maintenance of a closed urethral tube. These results demonstrate that urethral tubulogenesis, prepuce morphogenesis, and sexually dimorphic patterning of the lower urethra are controlled by discrete regions of Fgfr2 activity. © 2015. Published by The Company of Biologists Ltd. KEYWORDS: Fgf; Genitalia; Mouse; Sexual differentiation; Tubulogenesis; Urethra
Switching on sex: transcriptional regulation of the testis-determining gene Sry
Development. 2014 Jun;141(11):2195-205. doi: 10.1242/dev.107052.
Larney C1, Bailey TL1, Koopman P2.
Mammalian sex determination hinges on the development of ovaries or testes, with testis fate being triggered by the expression of the transcription factor sex-determining region Y (Sry). Reduced or delayed Sry expression impairs testis development, highlighting the importance of its accurate spatiotemporal regulation and implying a potential role for SRY dysregulation in human intersex disorders. Several epigenetic modifiers, transcription factors and kinases are implicated in regulating Sry transcription, but it remains unclear whether or how this farrago of factors acts co-ordinately. Here we review our current understanding of Sry regulation and provide a model that assembles all known regulators into three modules, each converging on a single transcription factor that binds to the Sry promoter. We also discuss potential future avenues for discovering the cis-elements and trans-factors required for Sry regulation. © 2014. Published by The Company of Biologists Ltd. KEYWORDS: Disorders of sex development; Sex determination; Sry; Testis development; Transcriptional regulation PMID 24866114
SRY interference of normal regulation of the RET gene suggests a potential role of the Y-chromosome gene in sexual dimorphism in Hirschsprung disease
Hum Mol Genet. 2014 Sep 28. pii: ddu488. [Epub ahead of print]
Li Y1, Kido T1, Garcia-Barcelo MM2, Tam PK2, Tabatabai ZL3, Lau YF4.
Abstract The Hirschsprung disease (HSCR) is a complex congenital disorder, arising from abnormalities in enteric nervous system (ENS) development. There is a gender disparity among the patients, with the male to female ratio as high as 5 : 1. Loss-of-function mutations of HSCR genes and haploinsufficiency of their gene products are the primary pathogenic mechanisms for disease development. Recent studies identified over half of the HSCR disease susceptibility genes as targets for the sex-determining factor SRY, suggesting that this Y-encoded transcription factor could be involved in sexual dimorphism in HSCR. Among the SRY targets, the tyrosine kinase receptor RET represents the most important disease gene, whose mutations account for half of the familial and up to one-third of the sporadic forms of HSCR. RET is regulated by a distal and a proximal enhancer at its promoter, in which PAX3 and NKX2-1 are the resident transcription factors respectively. We show that the SRY-box 10 (SOX10) co-activator interacts and forms transcriptional complexes with PAX3 and NKX2-1 in a sequence-independent manner and exacerbates their respective transactivation activities on the RET promoter. SRY competitively displaces SOX10 in such transcription complexes and represses their regulatory functions on RET. Hence SRY could be a Y-located negative modifier of RET expression; and if it is ectopically expressed during ENS development, such SRY repression could result in RET protein haploinsufficiency and promotion of HSCR development, thereby contributing to sexual dimorphism in HSCR. Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US. PMID 25267720
Modifications of Erectile Tissue Components in the Penis during the Fetal Period
PLoS One. 2014 Aug 29;9(8):e106409. doi: 10.1371/journal.pone.0106409. eCollection 2014.
Gallo CB1, Costa WS1, Furriel A1, Bastos AL2, Sampaio FJ1.
BACKGROUND: The penile erectile tissue has a complex microscopic anatomy with important functions in the mechanism of penile erection. The knowledge of such structures is necessary for understanding the normal physiology of the adult penis. Therefore, it is important to know the changes of these penile structures during fetal development. This study aims to analyze the development of the main components of the erectile tissue, such as collagen, smooth muscle fibers and elastic system fibers, in human fetuses. METHODOLOGY/PRINCIPAL FINDINGS: We studied the penises of 56 human fetuses aged 13 to 36 weeks post-conception (WPC). We used histochemical and immunohistochemical staining, as well as morphometric techniques to analyze the collagen, smooth muscle fibers and elastic system fibers in the corpus cavernosum and in the corpus spongiosum. These elements were identified and quantified as percentage by using the Image J software (NIH, Bethesda, USA). From 13 to 36 WPC, in the corpus cavernosum, the amount of collagen, smooth muscle fibers and elastic system fibers varied from 19.88% to 36.60%, from 4.39% to 29.76% and from 1.91% to 8.92%, respectively. In the corpus spongiosum, the amount of collagen, smooth muscle fibers and elastic system fibers varied from 34.65% to 45.89%, from 0.60% to 11.90% and from 3.22% to 11.93%, respectively. CONCLUSIONS: We found strong correlation between the elements analyzed with fetal age, both in corpus cavernosum and corpus spongiosum. The growth rate of these elements was more intense during the second trimester (13 to 24 WPC) of gestation, both in corpus cavernosum and in corpus spongiosum. There is greater proportional amount of collagen in the corpus spongiosum than in corpus cavernosum during all fetal period. In the corpus spongiosum, there is about four times more collagen than smooth muscle fibers and elastic system fibers, during all fetal period studied.
Normal male sexual differentiation and aetiology of disorders of sex development
Best Pract Res Clin Endocrinol Metab. 2011 Apr;25(2):221-38.
Rey RA, Grinspon RP. Source Centro de Investigaciones Endocrinológicas (CEDIE-CONICET), División de Endocrinología, Hospital de Niños Dr. Ricardo Gutiérrez, C1425EFD Buenos Aires, Argentina. email@example.com
Fetal sex development consists of three sequential stages: a) the undifferentiated stage, when identical primitive structures develop in the XY and XX embryos, b) gonadal differentiation into testes or ovaries, and c) the differentiation of internal and external genitalia, which depends on the action of testicular hormones. Disorders of sex development (DSD) may result from defects in any of these stages. Abnormal formation of the anlagen of internal and/or external genitalia in early embryonic development results in Malformative DSD. In patients with a Y chromosome, defects in testis differentiation drive to early-onset fetal hypogonadism affecting whole testicular function, a condition named Dysgenetic DSD. In Non-dysgenetic DSD, the underlying pathogenesis may involve early-onset fetal hypogonadism affecting specifically either Leydig or Sertoli cell function, or male hormone end-organ defects in patients devoid of fetal hypogonadism. Understanding the pathogenesis is useful for an efficient early diagnosis approach, which is necessary for adequate decision making in the management of DSD. Copyright © 2010 Elsevier Ltd. All rights reserved.
Second to fourth digit ratio: a predictor of adult penile length
Asian J Androl. 2011 Jul 4. doi: 10.1038/aja.2011.75. [Epub ahead of print]
Choi IH, Kim KH, Jung H, Yoon SJ, Kim SW, Kim TB. Source Department of Urology, Gachon University Gil Hospital, Incheon, Korea.
The second to fourth digit ratio (2D:4D) has been proposed as a putative biomarker for prenatal testosterone and covaries with the sensitivity of the androgen receptor (AR). Both prenatal testosterone and the AR play a central role in penile growth. In this study, we investigated the relationship between digit ratio and penile length. Korean men who were hospitalized for urological surgery at a single tertiary academic centre were examined in this study, and 144 men aged 20 years or older who gave informed consent were prospectively enrolled. Right-hand second- and fourth-digit lengths were measured by a single investigator prior to measurement of penile length. Under anaesthesia, flaccid and stretched penile lengths were measured by another investigator who did not measure nor have any the information regarding the digit lengths. Univariate and multivariate analysis using linear regression models showed that only height was a significant predictive factor for flaccid penile length (univariate analysis: r=0.185, P=0.026; multivariate analysis: r=0.172, P=0.038) and that only digit ratio was a significant predictive factor for stretched penile length (univariate analysis:r=-0.216, P=0.009; multivariate analysis: r=-0.201, P=0.024; stretched penile length=-9.201×digit ratio + 20.577). Based on this evidence, we suggest that the digit ratio can predict adult penile size and that the effects of prenatal testosterone may in part explain the differences in adult penile length.Asian Journal of Andrology advance online publication, 4 July 2011; doi:10.1038/aja.2011.75.
Penile biometry on prenatal MR imaging
Ultrasound Obstet Gynecol. 2011 Apr 12. doi: 10.1002/uog.9022. [Epub ahead of print]
Nemec SF, Nemec U, Weber M, Brugger PC, Bettelheim D, Rotmensch S, Krestan CR, Rimoin DL, Graham Jr JM, Prayer D.
Department of Radiology, Division of Neuroradiology and Musculoskeletal Radiology, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; Medical Genetics Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, PACT Suite 400, Los Angeles, California 90048, USA. firstname.lastname@example.org, email@example.com.
Abstract OBJECTIVE: In view of the implementation of magnetic resonance imaging (MRI) as an adjunct to ultrasonography (US) in prenatal diagnosis, this study sought to demonstrate normal penile growth on prenatal MRI.
MATERIALS AND METHODS: This retrospective study included MRI scans of 194 male fetuses (18 to 34 gestational weeks [GW]) with normal anatomy or minor abnormalities. On sagittal T2-weighted MR sequences, penile length was measured from the glans tip to the scrotal edge (outer length), and also, from the glans tip to the symphyseal border (total length). Statistical description, as well as correlation and regression analysis, were used to evaluate penile length in relation to gestation. T-tests were calculated to compare mean outer/total length on MRI with published US data.
RESULTS: Mean length values, including 95% confidence intervals and percentiles, were defined. Penile length as a function of gestational age was expressed by the regression equation: outer mean length= -5.514 + 0.622 *, and total mean length= -8.865 + 1.312 * (*= GW). The correlation coefficients were statistically significant (p < .001). The comparison between outer length on MRI and US data showed no significant differences, whereas total length on MRI and US data demonstrated significant differences (p< .001).
CONCLUSION: Our MRI results provide a reference range of fetal penile length, which, in addition to US, may be helpful in the identification of genital anomalies. Outer penile length on MRI is equivalent to penile length measured on US, whereas total length is significantly different. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
Xenografting of human fetal testis tissue: a new approach to study fetal testis development and germ cell differentiation
Hum Reprod. 2010 Oct;25(10):2405-14. Epub 2010 Aug 3.
Mitchell RT, Saunders PT, Childs AJ, Cassidy-Kojima C, Anderson RA, Wallace WH, Kelnar CJ, Sharpe RM.
MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. Abstract BACKGROUND: Abnormal fetal testis development can result in disorders of sex development (DSDs) and predispose to later testicular dysgenesis syndrome (TDS) disorders such as testicular germ cell tumours. Studies of human fetal testis development are hampered by the lack of appropriate model, and intervention systems. We hypothesized that human fetal testis xenografts can recapitulate normal development.
METHODS: Human fetal testes (at 9 weeks, n = 4 and 14-18 weeks gestation, n = 6) were xenografted into male nude mice for 6 weeks, with or without hCG treatment of the host, and evaluated for normal cellular development and function using immunohistochemistry, triple immunofluorescence and testosterone assay. The differentiation and proliferation status of germ cells within xenografts was quantified and compared with age-matched controls.
RESULTS: Xenografts showed >75% survival with normal morphology. In the first-trimester xenografts seminiferous cord formation was initiated and in first- and second-trimester grafts normal functional development of Sertoli, Leydig and peritubular myoid cells was demonstrated using cell-specific protein markers. Grafts produced testosterone when hosts were treated with hCG (P = 0.004 versus control). Proliferation of germ cells and differentiation from gonocytes (OCT4(+)) into pre-spermatogonia (VASA(+)) occurred in grafts and quantification showed this progressed comparably with age-matched ungrafted controls.
CONCLUSIONS: Human fetal testis tissue xenografts demonstrate normal structure, function and development after xenografting, including normal germ cell differentiation. This provides an in vivo system to study normal human fetal testis development and its susceptibility to disruption by exogenous factors (e.g. environmental chemicals). This should provide mechanistic insight into the fetal origins of DSDs and TDS disorders.
Growth and Development of Male External Genitalia: A Cross-sectional Study of 6200 Males Aged 0 to 19 Years
Arch Pediatr Adolesc Med. 2010 Dec;164(12):1152-7.
Tomova A, Deepinder F, Robeva R, Lalabonova H, Kumanov P, Agarwal A.
HCLD, Reproductive Research Center, Desk A19.1, Glickman Urological and Kidney Institute, and Department of Obstetric and Gynecology, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195. firstname.lastname@example.org.
OBJECTIVE: To provide estimates of normal variations in penile measurements and testicular volumes, and to establish reference ranges for clinical use.
DESIGN: Cross-sectional, population-based study.
SETTING: Schools, kindergartens, and child care centers in different parts of Bulgaria.
PARTICIPANTS: A population of 6200 clinically healthy white males aged 0 to 19 years.
INTERVENTIONS: The study physician chose schools, kindergartens, and child care centers randomly and examined children at random until he reached the required number. Each of the 20 age groups (age range, 0-19 years) had an equal number of males (ie, 310).
MAIN OUTCOME MEASURES: The mean (SD) values and fifth, 50th, and 95th percentiles of height (Siber Hegner anthropometer), weight (beam balance), testicular volume (Prader orchidometer), penile length (rigid tape), and penile circumference (measuring tape) from birth to 19 years of age.
RESULTS: Testes did not show any increase in size until the onset of puberty at age 11 years, whereas penile growth was gradual after birth. However, both penile and testicular development demonstrated peak growth from 12 to 16 years of age, which coincided with the maximal male pubertal growth spurt. Data indicate an earlier pubertal development for this study population than that for a similar population several decades ago. Significant differences between urban and rural populations regarding penile length were also noticed.
CONCLUSIONS: Our study provides the contemporary reference range values for height, weight, testicular volume, and penile length and circumference of males aged 0 to 19 years. Our data show that, even by the end of 20th century, there is still some acceleration of male pubertal development. For the first time are reported somatic differences in genitalia within a population between urban and rural representatives.
Penile embryology and anatomy
ScientificWorldJournal. 2010 Jun 29;10:1174-9.
Yiee JH, Baskin LS.
Department of Urology, University of California San Francisco, USA. email@example.com Abstract
Knowledge of penile embryology and anatomy is essential to any pediatric urologist in order to fully understand and treat congenital anomalies. Sex differentiation of the external genitalia occurs between the 7th and 17th weeks of gestation. The Y chromosome initiates male differentiation through the SRY gene, which triggers testicular development. Under the influence of androgens produced by the testes, external genitalia then develop into the penis and scrotum. Dorsal nerves supply penile skin sensation and lie within Buck's fascia. These nerves are notably absent at the 12 o'clock position. Perineal nerves supply skin sensation to the ventral shaft skin and frenulum. Cavernosal nerves lie within the corpora cavernosa and are responsible for sexual function. Paired cavernosal, dorsal, and bulbourethral arteries have extensive anastomotic connections. During erection, the cavernosal artery causes engorgement of the cavernosa, while the deep dorsal artery leads to glans enlargement. The majority of venous drainage occurs through a single, deep dorsal vein into which multiple emissary veins from the corpora and circumflex veins from the spongiosum drain. The corpora cavernosa and spongiosum are all made of spongy erectile tissue. Buck's fascia circumferentially envelops all three structures, splitting into two leaves ventrally at the spongiosum. The male urethra is composed of six parts: bladder neck, prostatic, membranous, bulbous, penile, and fossa navicularis. The urethra receives its blood supply from both proximal and distal directions.
Sonic hedgehog, apoptosis, and the penis
J Sex Med. 2009 Mar;6 Suppl 3:334-9.
Department of Urology, Northwestern University Medical School, Chicago, IL 60611, USA. firstname.lastname@example.org Abstract INTRODUCTION: Smooth muscle apoptosis in the penis is common in prostatectomy patients and animal models of erectile dysfunction (ED). A critical regulator of smooth muscle apoptosis in the penis is the secreted protein Sonic hedgehog (SHH). Since SHH protein treatment of the penis prevents cavernous nerve (CN) injury-induced apoptosis, SHH has the potential to treat post-prostatectomy apoptosis. However, little is known about how SHH signaling is regulated in the adult penis.
AIM: The goal of this review is to examine what is known about SHH signaling in the penis, to offer insight as to how SHH inhibition induces apoptosis in penile smooth muscle, and to define the role of the SHH pathway in maintaining CN integrity.
METHODS: Information presented in this review was derived from a literature search using the National Library of Medicine PubMed Services. Search terms included SHH, apoptosis, smooth muscle, penis, ED, pelvic ganglia, corpora cavernosa, CN, regeneration, Schwann cell, neural activity, and transport.
RESULTS: In this review, we have discussed the role of the CN in regulation of SHH abundance and apoptosis induction in the penis, and have examined the function and localization of SHH signaling in the CN.
CONCLUSION: There is substantial potential to develop SHH for delivery to the penis of prostatectomy patients at the time of surgery in order to prevent apoptosis induction and long-term ED development. Studies are in progress that will identify if SHH may be used as a regenerative therapy to speed CN regeneration.
The adrenal cortex and sexual differentiation during early human development
Rev Endocr Metab Disord. 2009 Mar;10(1):43-9.
Asby DJ, Arlt W, Hanley NA. Source Human Genetics Division, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, UK. Abstract Human sexual differentiation is a critical process whereby a strict dimorphism is established that enables future reproductive success as phenotypic males and females. Significant components of this differentiation pathway unfold during the first three months of gestation when they are sensitive to disruption by abnormal hormonal influences. Excessive exposure of female development to androgens in conditions such as congenital adrenal hyperplasia causes virilization. However, recently we have suggested that female development normally takes place in the presence of low, yet significant, levels of androgen, implying a need for strict regulation to avoid virilization and the potential for a biological role of androgens in females that has not been fully elucidated. Here, we review androgen-dependent male differentiation of the external genitalia in humans, and link this to current understanding of female development and steroidogenesis in the developing adrenal cortex.
Anatomy of the human penis: the relationship of the architecture between skeletal and smooth muscles
J Androl. 2004 May-Jun;25(3):426-31.
Hsu GL, Hsieh CH, Wen HS, Hsu WL, Wu CH, Fong TH, Chen SC, Tseng GF. Source Microsurgical Potency Reconstruction Center, Taiwan Adventist Hospital, Taipei Medical University Hospital, Taipei, Taiwan, Republic of China. email@example.com Abstract To investigate the anatomy of the ischiocavernosus muscle, bulbospongiosus muscle, and tunica albuginea and to determine their relationships to smooth muscle, which is a key element of penile sinusoids, we performed cadaveric dissection and histologic examinations of 35 adult human male cadavers. The tunica of the corpora cavernosa is a bilayered structure that can be divided into an inner circular layer and an outer longitudinal layer. The outer longitudinal layer is an incomplete coat that is absent between the 5-o'clock and 7-o'clock positions where 2 triangular ligamentous structures form. These structures, termed the ventral thickening, are a continuation of the anterior fibers of the left and right bulbospongiosus muscles. On the dorsal aspect, between the 1-o'clock and 11-o'clock positions, is a region called the dorsal thickening, a radiating aspect of the bilateral ischiocavernosus muscles. In the corpora cavernosa, skeletal muscle contains and supports smooth muscle, which is an essential element in the sinusoids. This relationship plays an important part in the blood vessels' ability to supply the blood to meet the requirements for erection, whereas in the corpus spongiosum, skeletal muscle partially entraps the smooth muscle to allow ejaculation when erect. In the glans penis, however, the distal ligament, a continuation of the outer longitudinal layer of the tunica, is arranged centrally and acts as a trunk of the glans penis. Without this strong ligament, the glans would be too weak to bear the buckling pressure generated during coitus. A significant difference exists in the thickness of the dorsal thickening, the ventral thickening, and the distal ligament between the potent and impotent groups (P < or =.01). Together, the anatomic relationships between skeletal muscle and smooth muscle within the human penis explain many physiologic phenomena, such as erection, ejaculation, the intracavernous pressure surge during ejaculation, and the pull-back force against the glans penis during anal constriction. This improvement in the modeling of the anatomic-physiologic relationship between these structures has clinical implications for penile surgeries.
Neuroanatomical ontogeny of the human fetal penis
Br J Urol. 1997 Apr;79(4):628-40.
Baskin LS, Lee YT, Cunha GR.
Department of Urology, University of California School of Medicine San Francisco, USA. Abstract OBJECTIVE: To determine the development of the human penis, and hence the cause of congenital anomalies, using an immunohistochemical analysis of fetal penile ontogeny.
MATERIALS AND METHODS: In 25 human fetal penile specimens (gestational age 8 to 23 weeks) various tissues were localized immunohistochemically using stains for alpha-actin (smooth muscle), cytokeratin 8 and 14 (epithelium) and protein gene-product (PGP) 9.5 (neurons).
RESULTS: Nerves were identified in the penis with anti-PGP in specimens of all ages, prominent dorsally at the 11 and 1 o'clock positions but also extending around the tunica to the junction of the corpus spongiosum and corpora cavernosa, suggesting that these structures may be injured in procedures which straighten the penis. The nerves continued into the glans on the dorsal aspect, suggesting that glans reduction in feminizing genitoplasties should be performed on the ventral aspect. Smooth muscle was first noted at 10 weeks' gestation, with epithelial differentiation occurring in the earliest specimens studied (8 weeks' gestation). With time, smooth muscle density was highest in the corpus spongiosum, especially between it and the corpora cavernosa. Smooth muscle also developed close to the urethral epithelium. The tunica albuginea showed consistent variations in thickness, with the mid-dorsal 12 o'clock position being the thickest, followed by the 5 and 7 o'clock periurethral positions.
CONCLUSION: A better knowledge of penile development and of the relationship of the nerves to the corpora cavernosa is useful in the strategic design of penile straightening procedures and feminizing genitoplasties.