Tet methylcytosine dioxygenase 2(TET2)-dependent epigenetic regulation in the pathogenesis of polycystic ovary syndrome - PubMed
a day ago
- #PCOS
- #Epigenetics
- #TET2
- Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder and a major cause of female infertility.
- Epigenetic dysregulation, particularly DNA methylation, plays a key role in PCOS pathogenesis.
- TET2-mediated 5-hydroxymethylcytosine (5hmC) modifications are involved in PCOS development.
- Genome-wide 5hmC profiling showed higher global 5hmC levels and TET2 expression in PCOS granulosa cells.
- Significant 5hmC alterations were found in pathways related to MAPK signaling, gap junction communication, and oocyte meiosis.
- USP45 was identified as a downstream target of TET2 via ChIP-seq analysis.
- TET2 drives hyperandrogenism-induced autophagy by stabilizing PRKAA1 through USP45-mediated deubiquitination.
- Pharmacological inhibition of TET2 rescued autophagic abnormalities in PCOS.
- The study provides a novel epigenetic framework for developing PCOS therapies.