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14 April 2018 Organizational effects of the antiandrogen, vinclozolin, on penis development in the mouse
Ciro M. Amato, Morgan Boyd, Joshua Yang, Krista A. McCoy
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Endocrine disrupting chemicals (EDCs) are pollutants found throughout the environment that disrupt normal endocrine processes. In mice, penis development is thought to be most susceptible to EDCs during a critical developmental window occurring on embryonic days (E) 15.5–17.5. However, androgen signaling begins on E13.5 when androgen receptor (AR) protein is found in the genitalia and testosterone is circulating. We hypothesize that disrupting androgen signaling prior to the established critical window sensitizes the penis to future androgen disruption. To test this hypothesis, CD1 dams were exposed to vinclozolin or a corn oil solvent control on E13.5 and E14.5 and AR levels were measured with immunohistochemistry on E14.5. Early antiandrogen exposure reduced AR within nuclei and decreased intensity of AR expression within E14.5 genitalia. To evaluate the influence of antiandrogen exposure before the known critical window of penis development, two groups of pregnant dams (n = 3) were exposed to vinclozolin starting at either E13.5 or E14.5 and continued exposure through E16.5. Histology andM.O.U.S.E. scoring were used to quantify penis abnormalities. To account for differences in total doses mice experienced due to differences in length of dosing time, we compared animals that received the same total doses. Exposure to antiandrogens on E13.5 exacerbated malformations when exposure was continued through sexually dimorphic development. Both exposure time and vinclozolin dose are important for severity of vinclozolin-induced penis abnormalities in mice. This work shows that antiandrogen exposure prior to sensitive periods can exacerbate the effects of later antiandrogen exposure on reproductive development.

Summary Sentence

Prior to the sensitive window the penis is responsive to antiandrogen exposure, and this early exposure exacerbates antiandrogen-induced penis abnormalities.

© The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail:
Ciro M. Amato, Morgan Boyd, Joshua Yang, and Krista A. McCoy "Organizational effects of the antiandrogen, vinclozolin, on penis development in the mouse," Biology of Reproduction 99(3), 639-649, (14 April 2018).
Received: 27 November 2017; Accepted: 12 April 2018; Published: 14 April 2018
androgens/androgen receptor
developmental biology
developmental origins of health and disease
endocrine disruptors
fetal development
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