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.
Highlights
Androgen signalling is a critical driver of male development
Circulating biomarkers characteristic of the sons of women with polycystic ovary syndrome (PCOS) were examined in male sheep from control and prenatally androgen treated pregnancies
anti-Müllerian hormone (AMH) and insulin were significantly elevated in adolescent prenatally androgen treated males (P < 0.05), but testosterone concentrations were comparable with control offspring (Fig. 1a)
Summary
Androgen signalling is a critical driver of male development. Fetal steroid signalling can be dysregulated by a range of environmental insults and clinical conditions. 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. Human data and animal experimentation has demonstrated aetiological contributions of prenatal androgen overexposure to the development of PCOS in female offspring[13], linking the reproductive phenotype with metabolic phenotypes, including insulin resistance (IR), obesity and dyslipidaemia. The aims of the study were, in an animal model of prenatal androgen excess: 1. Determine whether dyslipidaemia observed in PCOS-patient male relatives may have early-life-environment contributions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
