Transcriptomic mapping of key reproductive and metabolic tissues and oocytes in mouse models of polycystic ovary syndrome

Abstract

Excessive androgen production and obesity are key to Polycystic ovary syndrome (PCOS) pathogenesis. PCOS-like mouse models induced by androgen exposure include the prenatal androgenized (PNA), peripubertal androgenized, and overexpression of nerve growth factor in theca cells (17NF), as well as the effect of diet-induced maternal obesity model on offspring. To reveal the molecular features of these models, we performed transcriptomic profiling of the hypothalamus, adipose tissue, ovary, and MII oocytes. The largest number of differentially expressed genes (DEGs) were found in the ovaries of 17NF and in the adipose tissues of peripubertal androgenized models. In contrast, the hypothalamus is most affected in PNA and maternal obesity models suggesting fetal programming effects. The Ms4a6e gene, membrane-spanning 4-domains subfamily A member 6E, a DEG identified in the adipose tissue in all PCOS-like mouse models is also differently expressed in adipose tissue of women with PCOS women, highlighting a conservative disease mechanism. Our comprehensive transcriptomic mapping of key target tissues of the PCOS pathology provides a unique resource when investigating molecular mechanisms induced by androgen exposure and highlights that there are critical windows for androgen administration and maternal obesity.