Fetal androgen exposure is a determinant of adult male metabolic health

Katarzyna Siemienowicz, Panagiotis Filis, Sophie Shaw, Alex Douglas, Jennifer Thomas, Sally Mulroy, Forbes Howie, Paul A Fowler , W. Colin Duncan, Mick T Rae* (Corresponding Author)

*Corresponding author for this work

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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.
Original languageEnglish
Article number20195
JournalScientific Reports
Volume9
DOIs
Publication statusPublished - 27 Dec 2019

Keywords

  • developmental biology
  • disease model
  • Dyslipidaemias
  • endocrine system and metabolic diseases
  • endocrinology
  • metabolic diseases
  • metabolism
  • physiology

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