Endocrine Abstracts

In a register-based and case-control studies it has been shown that daughters of women with or without PCOS have a five-fold increased risk of being diagnosed with the syndrom. Moreover, sons born to a mother with PCOS have two to three-fold increased risk of being obese. But how PCOS is inherited is unclear as PCOS loci identified by genome-wide association studies account for only 10% of the heritability. It has been suggested that epigenetic and developmental programming contributes to the inheritance of PCOS. In support for this, PCOS-like traits induced by androgen exposure during pregnancy in mice can be passed on from mothers (F₀) to daughters (F₁), granddaughters (F₂), and even great-granddaughters (F₃), and transcriptional and mitochondrial perturbations of oocytes accompany the transmission. Several of the oocyte gene signatures are detectable also in serum from daughters of women with PCOS and in adipose tissue of unrelated women with PCOS, indicating communication between germ cells, serum and somatic tissues/cells. Also, male offspring F₁ to F₃ of obese and androgen-exposed mothers develop aberrant reproductive and metabolic traits in adulthood. Small-noncoding (snc)RNA sequencing carried by the sperm contribute to a transgenerational epigenetic inheritance of phenotypic traits. As in females, several of sperm signatures are detectable in whole blood from sons of women with PCOS supporting the translational relevance of the mouse findings.