Dyslipidaemia and altered hepatic function in males - consequences of androgen excess in fetal life

Siemienowicz, Katarzyna; Filis, Panagiotis; Shaw, Sophie; Douglas, Alex; Thomas, Jennifer; Howie, Forbes; Fowler, Paul; Duncan, Colin; Rae, Mick

Abstract

Introduction: Adult male offspring of women with PCOS have increased dyslipidaemia, characterised by elevated triglycerides (TG), increased total and LDL-cholesterol (LDL-C), and hyperinsulinaemia. As altered intrauterine endocrine environments can ‘programme’ adverse health outcomes in adulthood we hypothesised that this dyslipidaemia was a consequence of a hyperandrogenic intrauterine environment. We used an outbred large animal model to identify if prenatal androgen excess could be causally linked to male hepatic dysfunction and investigate the underpinning mechanisms of dyslipidaemia.

Methods: Ovine fetuses were directly injected with a 200 μl bolus of testosterone propionate (PA; 20 mg) or vehicle control (C) at day 62 and 82 of gestation. Male adolescent offspring were studied at 6 months postnatal age (C, n=14; PA, n=14). Hepatic transcriptome and proteome were determined using Illumina RNA sequencing and liquid chromatography-mass spectrometer (LC-MS/MS), respectively. Plasma proteins and analytes were measured using LC-MS/MS, ELISA or benchtop biochemistry autoanalysers. Statistical analysis between C and PA groups was carried out using pairwise comparisons, with false discovery rate correction, accepting adjusted P

Citation

Siemienowicz, K., Filis, P., Shaw, S., Douglas, A., Thomas, J., Howie, F., Fowler, P., Duncan, C., & Rae, M. (2019, May). Dyslipidaemia and altered hepatic function in males - consequences of androgen excess in fetal life. Presented at 21st European Congress of Endocrinology, Lyon, France

• Presentation Conference Type: Conference Abstract
• Conference Name: 21st European Congress of Endocrinology
• Start Date: May 18, 2019
• End Date: May 21, 2019
• Publication Date: 2019
• Deposit Date: Aug 20, 2019
• Print ISSN: 1479-6848
• Electronic ISSN: 1479-6848
• Volume: 63
• Article Number: P669
• Series Title: Endocrine Abstracts
• DOI: https://doi.org/10.1530/endoabs.63.P669
• Public URL: http://researchrepository.napier.ac.uk/Output/1789301