Analysis of the effect of estrogen/androgen perturbation on penile development in transgenic and diethylstilbestrol-treated mice

Sarah D Blaschko, Phitsanu Mahawong, Max Ferritti, Tristan J Cunha, Adriane Sinclair, Hong Wang, Bruce J Schlomer, Gail Petuna Risbridger, Laurence S Baskin, Gerald R Cunha

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41 Citations (Scopus)

Abstract

Because both androgens and estrogens have been implicated in penile morphogenesis, we evaluated penile morphology in transgenic mice with known imbalance of androgen and estrogen signaling using scanning electron microscopy (SEM), histology, and immunohistochemistry of androgen and estrogen receptors alpha/beta. Penises of adult wild-type, estrogen receptor-alpha knockout (alphaERKO), estrogen receptor-beta knockout (betaERKO), aromatase knockout (Arom-KO), and aromatase overexpression (Arom+) mice were evaluated, as well as adult mice treated with diethylstilbestrol (DES) from birth to day 10. Adult penises were examined because the adult pattern is the endpoint of development. The urethral orifice is formed by fusion of the MUMP (male urogenital mating protuberance) with the MUMP ridge, which consists of several processes fused to each other and to the MUMP. Similarly, the internal prepuce is completed ventrally by fusion of a ventral cleft. In adult murine penises the stromal processes that form the MUMP ridge are separated from their neighbors by clefts. alphaERKO, betaERKO, and Arom-KO mice have penises with a MUMP ridge clefting pattern similar to that of wild-type mice. In contrast, Arom+ mice and neonatally DES-treated mice exhibit profound malformations of the MUMP, MUMP ridge clefting pattern, and internal prepuce. Abnormalities observed in Arom+ and neonatally DES-treated mice correlate with the expression of estrogen receptor-beta (ERbeta) in the affected structures. This study demonstrates that formation of the urethal orifice and internal prepuce is due to fusion of separate epithelial-surfaced mesenchymal elements, a process dependent upon both androgen and estrogen signaling, in which ERbeta signaling is strongly implicated. Anat Rec, 296:1127-1141, 2013. (c) 2013 Wiley Periodicals, Inc.
Original languageEnglish
Pages (from-to)1127 - 1141
Number of pages15
JournalAnatomical Record
Volume296
Issue number7
DOIs
Publication statusPublished - 2013

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