Insights into the effects of sex and tissue location on the evolution of adipocyte dysfunction in an ovine model of polycystic ovary syndrome (PCOS).

Levate, Giovanni; Wang, Yuan; McCredie, Riada; Fenwick, Megan; Rae, Michael T.; Duncan, W. Colin; Siemienowicz, Katarzyna J.

Abstract

Adipose tissue dysfunction is one of the features of Polycystic Ovary Syndrome (PCOS) with dysregulated adipogenesis, altered functional pathways and increased inflammation. It is increasingly clear that there are also male correlates of the hormonal and metabolic features of PCOS. We hypothesised that the effects of adipose tissue dysfunction are not sex-specific but rather fat depot-specific and independent of obesity. We used a clinically realistic ovine model of PCOS where pregnant sheep are injected with 100mg of testosterone propionate twice weekly from day 62 to day 102 of gestation. We studied control and prenatally androgenised (PA) female and male offspring during adolescence and weight-matched control and PA female sheep during adulthood. We examined subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and in adult female sheep bone marrow adipose tissue (BMAT). Adipogenesis related gene expression in SAT was similar in adolescent female and male controls and the reduction in adipogenesis related gene expression by PA in female adipose tissue was not observed in males. Differences in expression of genes associated with adipose tissue function in adolescence in SAT driven by PA were found in both sexes. In adulthood, the changes seen in adolescent females were absent or reversed but there was an increase in inflammatory markers that was weight independent. In addition, BMAT showed increased inflammatory markers. Adipose dysfunction evolves with time and is focussed on SAT rather than VAT and is generally sex-specific although there are also effects of prenatal androgenisation on male SAT. In female adults, the inflammation seen in SAT is also present in BMAT and the development of blood cells in an inflammatory environment may have systemic implications.

Citation

Levate, G., Wang, Y., McCredie, R., Fenwick, M., Rae, M. T., Duncan, W. C., & Siemienowicz, K. J. (2025). Insights into the effects of sex and tissue location on the evolution of adipocyte dysfunction in an ovine model of polycystic ovary syndrome (PCOS). Molecular and Cellular Endocrinology, 595, Article 112416. https://doi.org/10.1016/j.mce.2024.112416

• Journal Article Type: Article
• Acceptance Date: Nov 13, 2024
• Online Publication Date: Nov 16, 2024
• Publication Date: Jan 1, 2025
• Deposit Date: Nov 18, 2024
• Publicly Available Date: Nov 18, 2024
• Journal: Molecular and Cellular Endocrinology
• Print ISSN: 0303-7207
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 595
• Article Number: 112416
• DOI: https://doi.org/10.1016/j.mce.2024.112416
• Keywords: Androgen, Bone Marrow, Adipose tissue, inflammation, sex differences, Sheep