Centre for Reproductive Health, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, UK.
Centre for Biomedicine and Global Health, Edinburgh Napier University, Edinburgh, UK.
Mol Cell Endocrinol. 2025 Jan 1;595:112416. doi: 10.1016/j.mce.2024.112416. Epub 2024 Nov 16.
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 100 mg 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.
脂肪组织功能障碍是多囊卵巢综合征（PCOS）的特征之一，其表现为脂肪生成失调、功能途径改变和炎症增加。越来越明显的是，PCOS 的激素和代谢特征也存在男性相关因素。我们假设，脂肪组织功能障碍的影响不是性别特异性的，而是脂肪库特异性的，与肥胖无关。我们使用了一种临床现实的 PCOS 绵羊模型，在该模型中，从妊娠第 62 天到第 102 天，每周两次向怀孕绵羊注射 100 毫克丙酸睾酮。我们在青春期研究了对照和产前雄激素化（PA）的雌性和雄性后代，以及成年时体重匹配的对照和 PA 雌性绵羊。我们检查了皮下脂肪组织（SAT）、内脏脂肪组织（VAT）和成年雌性绵羊骨髓脂肪组织（BMAT）。青春期雌性和雄性对照的 SAT 中与脂肪生成相关的基因表达相似，而 PA 对雌性脂肪组织中与脂肪生成相关的基因表达的降低在雄性中并未观察到。在 SAT 中，由 PA 驱动的青春期与脂肪组织功能相关的基因表达的差异在两性中都存在。在成年期，青春期女性中观察到的变化消失或逆转，但与体重无关的炎症标志物增加。此外，BMAT 显示出炎症标志物增加。脂肪功能障碍随时间演变，主要集中在 SAT 而不是 VAT，并且通常是性别特异性的，尽管产前雄激素化对雄性 SAT 也有影响。在成年女性中，SAT 中存在的炎症也存在于 BMAT 中，在炎症环境中发育的血细胞可能具有全身影响。
