Development of the external genitalia: Perspectives from the spotted hyena (Crocuta crocuta)

Abstract

This review/research paper summarizes data on development of the external genitalia of the spotted hyena, a fascinating mammal noted for extreme masculinization of the female external genitalia. The female spotted hyena is the only extant mammal that mates and gives birth through a pendulous penis-like clitoris. Our studies indicate that early formation of the phallus in both males and females is independent of androgens; indeed the phallus forms before the fetal testes or ovaries are capable of synthesizing androgens. Likewise, pre- and postnatal growth in length of the penis and clitoris is minimally affected by “androgen status”. Nonetheless, several internal morphologies, as well as external surface features of the phallus, are androgen-dependent and thus account for dimorphism between the penis and clitoris. Finally, estrogens play a critical role in penile and clitoral development, specifying the position of the urethral orifice, determining elasticity of the urethral meatus, and facilitating epithelial-epithelial fusion events required for proper formation of the distal urethra/urogenital sinus and prepuce. Accordingly, prenatal inhibition of estrogen synthesis via administration of letrozole (an aromatase inhibitor) leads to malformations of the glans as well as the prepuce (hypospadias). The effects of prenatal androgens, anti-androgens and impaired estrogen synthesis correlated with the tissue expression of androgen and estrogen receptors.

Canalization of the Vestibular Plate in the Absence of Urethral Fusion Characterizes Development of the Human Clitoris: The Single Zipper Hypothesis

“…There is a precedent for androgen independent growth of the clitoris in the spotted hyena. 14 To our knowledge the mechanism remains to be determined but it is possible that estrogens have a role in this process.…”

The Evolutionary Origin of Female Orgasm

“…This is indicative of the importance of clitoral position for the human female orgasm. It should be noted that the size of the clitoris in mammals is very sensitive to the androgen exposure during fetal development (Cunha et al., ), which in its extreme form can manifest as masculinized external (and internal) female genitalia—as occurs occasionally in multiple species (“freemartins”; Smith and Dunn, ; Braun et al., ; Padula, ; Drea and Weil, ), and are even the normal characteristics in some, as is best known of hyena and fossa (Neaves et al., ; Hawkins et al., ) and to some extent spider monkey (Dixson, ). As androgen level may be affected by selection on its other functions (for instance, aggression; French et al., ), the variation in clitoral length could certainly be affected indirectly as well.…”

Comparative Morphology of the Penis and Clitoris in Four Species of Moles (Talpidae)

“…The question concerning the mechanism of masculinization of female external genitalia is generally approached as an issue of androgen action, with exploration for a source of androgens, and if possible (rarely), with experimental studies of the effects of various forms of “androgen blockade/deprivation”. While female fetuses of spotted hyenas are exposed to endogenous androgens (Licht et al., ), formation and growth of the pendulous penile clitoris of the spotted hyena is androgen independent even though development of certain internal phallic structures is androgen dependent (Cunha et al., ). Transient masculinization of the clitoris of Fossa fossana is not associated with elevated female androgen levels (Hawkins et al., ).…”

“…This idea is consistent with regulation of AGD in mice, which is affected by intrauterine position, but cannot be reduced in females below a certain point as a result of prenatal treatment with an antiandrogen (Vom Saal, ; vom Saal and Bronson, ; Mitchell et al., ). Thus, there is precedent for the idea that certain aspects of male and female external genitalia may be androgen independent (Cunha et al., ).…”

“…In addition, the clitoris is associated with a vaginal opening (at least during the breeding season). Moles, ring‐tailed lemurs ( Lemur catta ), and spotted hyenas ( Crocuta crocuta ) are extreme examples of masculinization of female external genitalia (Matthews, ; Drea and Weil, ; Cunha et al., ). For these species, the terms penile clitoris and peniform clitoris have been used to describe their external genitalia.…”