PMID- 23653160 OWN - NLM STAT- MEDLINE DCOM- 20131021 LR - 20211021 IS - 1932-8494 (Electronic) IS - 1932-8486 (Print) IS - 1932-8486 (Linking) VI - 296 IP - 7 DP - 2013 Jul TI - Analysis of the effect of estrogen/androgen perturbation on penile development in transgenic and diethylstilbestrol-treated mice. PG - 1127-41 LID - 10.1002/ar.22708 [doi] AB - 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. CI - Copyright (c) 2013 Wiley Periodicals, Inc. FAU - Blaschko, Sarah D AU - Blaschko SD AD - Department of Urology, University of California San Francisco, A610 San Francisco, California, USA. FAU - Mahawong, Phitsanu AU - Mahawong P FAU - Ferretti, Max AU - Ferretti M FAU - Cunha, Tristan J AU - Cunha TJ FAU - Sinclair, Adriane AU - Sinclair A FAU - Wang, Hong AU - Wang H FAU - Schlomer, Bruce J AU - Schlomer BJ FAU - Risbridger, Gail AU - Risbridger G FAU - Baskin, Laurence S AU - Baskin LS FAU - Cunha, Gerald R AU - Cunha GR LA - eng GR - R01 DK058105/DK/NIDDK NIH HHS/United States GR - R01 DK0581050/DK/NIDDK NIH HHS/United States GR - APP1002733/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20130508 PL - United States TA - Anat Rec (Hoboken) JT - Anatomical record (Hoboken, N.J. : 2007) JID - 101292775 RN - 0 (Estrogen Receptor alpha) RN - 0 (Estrogen Receptor beta) RN - 0 (Estrogens, Non-Steroidal) RN - 731DCA35BT (Diethylstilbestrol) RN - EC 1.14.14.1 (Aromatase) SB - IM MH - Age Factors MH - Animals MH - Animals, Newborn MH - Aromatase/deficiency/genetics/*metabolism MH - Diethylstilbestrol/*toxicity MH - Estrogen Receptor alpha/deficiency/genetics/*metabolism MH - Estrogen Receptor beta/deficiency/genetics/*metabolism MH - Estrogens, Non-Steroidal/*toxicity MH - Immunohistochemistry MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mice, Transgenic MH - Microscopy, Electron, Scanning MH - Morphogenesis/drug effects MH - Penis/abnormalities/*drug effects/metabolism MH - Signal Transduction/drug effects PMC - PMC3709018 MID - NIHMS491246 EDAT- 2013/05/09 06:00 MHDA- 2013/10/22 06:00 PMCR- 2014/07/01 CRDT- 2013/05/09 06:00 PHST- 2013/02/06 00:00 [received] PHST- 2013/03/27 00:00 [accepted] PHST- 2013/05/09 06:00 [entrez] PHST- 2013/05/09 06:00 [pubmed] PHST- 2013/10/22 06:00 [medline] PHST- 2014/07/01 00:00 [pmc-release] AID - 10.1002/ar.22708 [doi] PST - ppublish SO - Anat Rec (Hoboken). 2013 Jul;296(7):1127-41. doi: 10.1002/ar.22708. Epub 2013 May 8.