Polycystic ovary syndrome is transmitted via a transgenerational epigenetic process
Mimouni et. al.
Polycystic ovary syndrome(PCOS) is the most common reproductive andmetabolic disorderaffecting women of reproductive age. PCOS has a strong heritable component, but its pathogenesis has been unclear. Here, we performedRNA sequencingand genome-wideDNA methylationprofiling of ovarian tissue from control and third-generation PCOS-like mice. We found that DNA hypomethylation regulates key genes associated with PCOS and that several of the differentially methylated genes are also altered in blood samples from women with PCOS compared with healthy controls. Based on this insight, we treated the PCOS mouse model with themethyl groupdonor S-adenosylmethionine and found that it corrected theirtranscriptomic, neuroendocrine, and metabolic defects. These findings show that the transmission of PCOS traits to future generations occurs via an altered landscape of DNA methylation and propose methylome markers as a possible diagnostic landmark for the condition, while also identifying potential candidates for epigenetic-based therapy.
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