Edinburgh Napier University

  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