Fetal androgen exposure is a determinant of adult male metabolic health

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. Te...

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Autores principales:	Katarzyna J. Siemienowicz, Panagiotis Filis, Sophie Shaw, Alex Douglas, Jennifer Thomas, Sally Mulroy, Forbes Howie, Paul A. Fowler, W. Colin Duncan, Mick T. Rae
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ee541a7cd4c64f42a9378b61e15ec36b
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spelling	oai:doaj.org-article:ee541a7cd4c64f42a9378b61e15ec36b2021-12-02T13:35:11ZFetal androgen exposure is a determinant of adult male metabolic health10.1038/s41598-019-56790-42045-2322https://doaj.org/article/ee541a7cd4c64f42a9378b61e15ec36b2019-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-56790-4https://doaj.org/toc/2045-2322Abstract 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.Katarzyna J. SiemienowiczPanagiotis FilisSophie ShawAlex DouglasJennifer ThomasSally MulroyForbes HowiePaul A. FowlerW. Colin DuncanMick T. RaeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-17 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Katarzyna J. Siemienowicz Panagiotis Filis Sophie Shaw Alex Douglas Jennifer Thomas Sally Mulroy Forbes Howie Paul A. Fowler W. Colin Duncan Mick T. Rae Fetal androgen exposure is a determinant of adult male metabolic health
description	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.
format	article
author	Katarzyna J. Siemienowicz Panagiotis Filis Sophie Shaw Alex Douglas Jennifer Thomas Sally Mulroy Forbes Howie Paul A. Fowler W. Colin Duncan Mick T. Rae
author_facet	Katarzyna J. Siemienowicz Panagiotis Filis Sophie Shaw Alex Douglas Jennifer Thomas Sally Mulroy Forbes Howie Paul A. Fowler W. Colin Duncan Mick T. Rae
author_sort	Katarzyna J. Siemienowicz
title	Fetal androgen exposure is a determinant of adult male metabolic health
title_short	Fetal androgen exposure is a determinant of adult male metabolic health
title_full	Fetal androgen exposure is a determinant of adult male metabolic health
title_fullStr	Fetal androgen exposure is a determinant of adult male metabolic health
title_full_unstemmed	Fetal androgen exposure is a determinant of adult male metabolic health
title_sort	fetal androgen exposure is a determinant of adult male metabolic health
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/ee541a7cd4c64f42a9378b61e15ec36b
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Fetal androgen exposure is a determinant of adult male metabolic health

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