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

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

Research output: Contribution to journalArticle

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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 α/β. Penises of adult wild-type, estrogen receptor-α knockout (αERKO), estrogen receptor-β knockout (βERKO), 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. αERKO, βERKO, 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 (ERβ) 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 ERβ signaling is strongly implicated.

Original languageEnglish (US)
Pages (from-to)1127-1141
Number of pages15
JournalAnatomical Record
Volume296
Issue number7
DOIs
StatePublished - Jul 2013

Fingerprint

diethylstilbestrol
Diethylstilbestrol
androgen
androgens
Androgens
estrogens
Estrogens
perturbation
genetically modified organisms
Estrogen Receptors
Penis
mice
Aromatase
penis
prepuce
Estrogen Receptor beta
morphogenesis
histology
Androgen Receptors
abnormality

Keywords

  • Androgen receptor
  • Estrogen receptor
  • Mouse penis
  • Prepuce

ASJC Scopus subject areas

  • Anatomy
  • Histology
  • Ecology, Evolution, Behavior and Systematics
  • Biotechnology

Cite this

Blaschko, S. D., Mahawong, P., Ferretti, M., Cunha, T. J., Sinclair, A., Wang, H., ... Cunha, G. R. (2013). Analysis of the effect of estrogen/androgen perturbation on penile development in transgenic and diethylstilbestrol-treated mice. Anatomical Record, 296(7), 1127-1141. https://doi.org/10.1002/ar.22708

Analysis of the effect of estrogen/androgen perturbation on penile development in transgenic and diethylstilbestrol-treated mice. / Blaschko, Sarah D.; Mahawong, Phitsanu; Ferretti, Max; Cunha, Tristan J.; Sinclair, Adriane; Wang, Hong; Schlomer, Bruce J.; Risbridger, Gail; Baskin, Laurence S.; Cunha, Gerald R.

In: Anatomical Record, Vol. 296, No. 7, 07.2013, p. 1127-1141.

Research output: Contribution to journalArticle

Blaschko, SD, Mahawong, P, Ferretti, M, Cunha, TJ, Sinclair, A, Wang, H, Schlomer, BJ, Risbridger, G, Baskin, LS & Cunha, GR 2013, 'Analysis of the effect of estrogen/androgen perturbation on penile development in transgenic and diethylstilbestrol-treated mice', Anatomical Record, vol. 296, no. 7, pp. 1127-1141. https://doi.org/10.1002/ar.22708
Blaschko, Sarah D. ; Mahawong, Phitsanu ; Ferretti, Max ; Cunha, Tristan J. ; Sinclair, Adriane ; Wang, Hong ; Schlomer, Bruce J. ; Risbridger, Gail ; Baskin, Laurence S. ; Cunha, Gerald R. / Analysis of the effect of estrogen/androgen perturbation on penile development in transgenic and diethylstilbestrol-treated mice. In: Anatomical Record. 2013 ; Vol. 296, No. 7. pp. 1127-1141.
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