Development of the Penis during the Human Fetal Period (13 to 36 Weeks after Conception)

Gallo, C.; Costa, Waldemar S.; Furriel, A.; Bastos, Ana L.; Sampaio, Francisco J.B.

doi:10.1016/j.juro.2013.05.050

Cited by 10 publications

(6 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Masculinization of the fetus is dependent on the action of testosterone at the Wolffian ducts and on the action of DHT at the external genitalia [25]. The process of masculinization at the external genitalia starts in the late first/early second trimester, and the most intense phase of penile growth occurs later in the second trimester [8]. This is a critical period for normal masculinization, therefore, and it was assumed until recently that growth of the external genitalia was solely dependent on DHT formed in the target organ through 5α-reduction of testis-derived testosterone.…”

Section: Discussionmentioning

confidence: 99%

“…In humans, male-specific morphological differentiation of the genital tubercle/penis begins around 10 weeks of gestation (i.e., 8 weeks postconception), with closure of the urethral groove [6,7]. The process is complete by about gestation weeks 15–16.5 [6,7], although sexually dimorphic growth of the penis continues through the second and third trimesters [8]. The etiology of hypospadias is probably multifactorial, but it is likely that altered androgen exposure during the second trimester is a significant factor [9].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Alternative (backdoor) androgen production and masculinization in the human fetus

et al. 2019

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alternative (backdoor) androgen production and masculinization in the human fetus

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Masculinization of the fetus is dependent on the action of testosterone at the Wolffian ducts and on the action of DHT at the external genitalia (19). The process of masculinization at the external genitalia starts in the early second trimester and the most intense phase of penile growth also occurs later in the second trimester (20). This is a critical period for normal masculinization, therefore, and it was assumed, until recently, that growth of the external genitalia was solely dependent on DHT formed in the target organ through 5α-reduction of testis-derived testosterone.…”

Section: Discussionmentioning

confidence: 99%

Alternative (backdoor) androgen production and masculinization in the human fetus

O’Shaughnessy

Antignac

Bizec

et al. 2018

Preprint

View full text Add to dashboard Cite

2Masculinization of the external genitalia in humans is dependent on formation of 5α-3 dihydrotestosterone (DHT) through both the canonical androgenic pathway and an alternative 4 (backdoor) pathway. The fetal testes are essential for canonical androgen production but little 5 is known about the synthesis of backdoor androgens despite their known critical role in 6 masculinization. In this study, we have measured plasma and tissue levels of endogenous 7 steroids in second trimester human male fetuses using multi-dimensional and high-resolution formed primarily in non-gonadal tissue with placental progesterone the likely substrate. 16Masculinization of the human fetus depends, therefore, on androgen synthesis by both the 17 fetal testes and non-gonadal tissues leading to DHT formation at the genital tubercle. Our 18 findings provide, for the first time, a solid basis to explain why placental insufficiency is

show abstract

“…The sex difference in AGD can already be observed in human foetuses at 11 to 13 weeks of gestation, and the sex difference increases to a magnitude similar to that at birth by 17 to 20 weeks of gestation (Thankamony et al, 2016). Similarly, in regard to androgen‐dependent penile development, the external genitalia are fully differentiated by around 12 weeks of gestation and penile growth appears to be more intense during mid‐gestation than late gestation (Gallo, Costa, Furriel, Bastos, & Sampaio, 2013; Johnson & Maxwell, 2000). In addition, both AGD and penile length increase rapidly during the first 3 months of life, which corresponds to the early postnatal testosterone surge (Thankamony, Ong, Dunger, Acerini, & Hughes, 2009).…”

Section: Introductionmentioning

confidence: 99%

No relationship between prenatal or early postnatal androgen exposure and autistic traits: evidence using anogenital distance and penile length measurements at birth and 3 months of age

Kung

Thankamony

Ong

et al. 2020

Child Psychology Psychiatry

View full text Add to dashboard Cite

Background: Autism is more prevalent in males than in females. Hypotheses related to the extreme male brain theory of autism suggest that heightened androgen exposure during early development contributes to autistic traits. Whilst prior research focused mostly on the prenatal period, the current study tests the influences of androgen exposure during both the prenatal and the early postnatal periods on autistic traits during childhood. Methods: Anthropometric measures that are putative biomarkers of early androgen exposure were employed. Anogenital distance (AGD) was measured at birth and 3 months of age in boys and girls. Penile length at birth and 3 months of age was also measured in boys. When the children were 9-13 years old, a parent-reported questionnaire (the 10-item children's version of the Autism Spectrum Quotient; AQ-10 Child) was used to assess autistic traits in 97 boys and 110 girls. Results: There were no significant associations between any of the AGD or penile length measures and scores on the AQ-10 Child in boys, girls or the entire sample. Conclusions: The current study provides the first test of whether early measurements of AGD and/or penile length predict subsequent autistic traits. The current findings do not support a relationship between prenatal or early postnatal androgen exposure and autistic traits. The current study augments prior research showing no consistent relationship between early androgen exposure and autistic traits.

show abstract

Development of the Penis during the Human Fetal Period (13 to 36 Weeks after Conception)

Cited by 10 publications

References 22 publications

Alternative (backdoor) androgen production and masculinization in the human fetus

Alternative (backdoor) androgen production and masculinization in the human fetus

Alternative (backdoor) androgen production and masculinization in the human fetus

No relationship between prenatal or early postnatal androgen exposure and autistic traits: evidence using anogenital distance and penile length measurements at birth and 3 months of age

Contact Info

Product

Resources

About