Journal article

A critical role for estrogen signaling in penis development

Luke C Govers, Tiffany R Phillips, Deidre M Mattiske, Nineveh Rashoo, Jay R Black, Adriane Sinclair, Laurence S Baskin, Gail P Risbridger, Andrew J Pask

The FASEB Journal | FEDERATION AMER SOC EXP BIOL | Published : 2019

Abstract

Hypospadias, a developmental defect of the penis, is one of the most common congenital malformations in humans. Its incidence has rapidly increased over recent decades, and this has been largely attributed to our increased exposure to endocrine-disrupting chemicals. Penis development is primarily an androgen-driven process; however, estrogen and xenoestrogens are known to affect penis development in both humans and mice. Here, we investigated the role of estrogen in the developing penis. Using a novel penis culture system, we showed that exogenous estrogen directly targets the developing penis in utero to cause hypospadias. In addition, we also uncovered an unexpected endogenous role for est..

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Grants

Awarded by U.S. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Grant


Awarded by National Health and Medical Research Council of Australia


Funding Acknowledgements

The authors acknowledge technical support by the Melbourne Trace Analysis for Chemical, Earth, and Environmental Sciences (TrACEES) Platform for access to the GE Phoenix Nanotom M Micro-CT instrument. Research reported in this publication was supported by the U.S. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Grant R01DK096263 (to A.J.P.), and by the National Health and Medical Research Council of Australia Project Grant APP1098480 (to G.P.R. and A.J.P.). The authors declare no conflicts of interest.