Fetal androgen exposure is a determinant of adult male metabolic health

Siemienowicz, Katarzyna J.; Filis, Panagiotis; Shaw, Sophie; Douglas, Alex; Thomas, Jennifer; Mulroy, Sally; Howie, Forbes; Fowler, Paul A.; Duncan, W Colin; Rae, Mick T.

Abstract

Androgen signalling is a critical driver of male development. Fetal steroid signalling can be dysregulated by a range of environmental insults and clinical conditions. We hypothesised that poor adult male health was partially attributable to aberrant androgen exposure during development. Testosterone was directly administered to developing male ovine fetuses to model excess prenatal androgenic overexposure associated with conditions such as polycystic ovary syndrome (PCOS). Such in utero androgen excess recreated the dyslipidaemia and hormonal profile observed in sons of PCOS patients. 1,084 of 15,134 and 408 of 2,766 quantifiable genes and proteins respectively, were altered in the liver during adolescence, attributable to fetal androgen excess. Furthermore, prenatal androgen excess predisposed to adolescent development of an intrahepatic cholestasis-like condition with attendant hypercholesterolaemia and an emergent pro-fibrotic, pro-oxidative stress gene and protein expression profile evident in both liver and circulation. We conclude that prenatal androgen excess is a previously unrecognised determinant of lifelong male metabolic health.

Citation

Siemienowicz, K. J., Filis, P., Shaw, S., Douglas, A., Thomas, J., Mulroy, S., Howie, F., Fowler, P. A., Duncan, W. C., & Rae, M. T. (2019). Fetal androgen exposure is a determinant of adult male metabolic health. Scientific Reports, 9, Article 20195 (2019). https://doi.org/10.1038/s41598-019-56790-4

• Journal Article Type: Article
• Acceptance Date: Dec 17, 2019
• Online Publication Date: Dec 27, 2019
• Publication Date: Dec 27, 2019
• Deposit Date: Dec 17, 2019
• Publicly Available Date: Jan 7, 2020
• Electronic ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Article Number: 20195 (2019)
• DOI: https://doi.org/10.1038/s41598-019-56790-4
• Public URL: http://researchrepository.napier.ac.uk/Output/2404291