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

Differentiation. 2014 pii: S0301-4681(13)00087-X
doi: 10.1016/j.diff.2013.12.003
Available online 28 February 2014
[Epub ahead of print]

Gerald R. Cunha [a,b], Gail Risbridger [b], Hong Wang [b], Ned J. Place [c], Mel Grumbach [d], Tristan J. Cunha [a], Mary Weldele [e], Al J. Conley [f], Dale Barcellos [g], Sanjana Agarwal [g], Argun Bhargava [g], Christine Drea [h], Geoffrey L. Hammond [i], Penti Siiteri [j], Elizabeth M. Coscia [k], Michael J. McPhaul [l], Laurence S. Baskin [a], Stephen E. Glickman [e]

[a] Department of Urology, University of California San Francisco, 400 Parnassus Avenue, Box A610, San Francisco, CA 94143, United States
[b] Department of Anatomy & Developmental Biology, Monash University, Clayton Campus, Building 76 Level 3, Wellington Road, Clayton, VIC, Australia
[c] Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States
[d] Department of Pediatrics, University of California San Francisco, Box 0434, San Francisco, CA 94143, United States
[e] Departments of Psychology and Integrative Biology, University of California, Berkeley, CA 94720, United States
[f] Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, United States
[g] Monte Vista High School, Cupertino, CA 95014, United States
[h] Departments of Evolutionary Anthropology and Biology, Duke University, Durham, NC 27708, United States
[i] Department of Cellular & Physiological Sciences, University of British Columbia, Vancouver, BC, Canada
[j] Department of Obstetrics and Gynecology, University of California San Francisco, 400 Parnassus Avenue, Box A610, San Francisco, CA 94143, United States
[k] Salesian High School, Richmond, CA 94804, United States
[l] University of Texas Southwestern, Division of Endocrinology and Metabolism, 5323 Harry Hines Blvd., Dallas, TX, 75390-8857 and Quest Diagnostics, Endocrine Division, 33608 Ortega Highway, San Juan Capistrano, CA 92675, United States

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.

http://www.sciencedirect.com/science/article/pii/S030146811300087X