Epigenetic/circadian clocks and PCOS

Area of Science:

• Endocrinology and Genetics
• Reproductive Medicine
• Epigenetics and Chronobiology

Background:

• Polycystic Ovary Syndrome (PCOS) affects 6-20% of women and is linked to metabolic syndrome, type 2 diabetes, cardiovascular disease, and endometrial cancer.
• Genetic studies explain only about 10% of PCOS heritability, indicating other factors are involved in its etiology.
• Epigenetic alterations and circadian clock gene modifications are increasingly recognized as potential contributors to PCOS pathogenesis.

Purpose of the Study:

• To review the role of epigenetic changes and circadian clock gene modifications in the development of Polycystic Ovary Syndrome (PCOS).
• To explore the potential of epigenetic modifications as diagnostic biomarkers and therapeutic targets for PCOS.

Main Methods:

• Review of existing literature on epigenetic alterations (DNA methylation, histone modifications, non-coding RNAs) in PCOS and related conditions.
• Analysis of animal models demonstrating epigenetic programming in PCOS-like phenotypes.
• Examination of human studies reporting epigenetic changes in various tissues (PBMC, adipose, GC, liver) of women with PCOS.

Main Results:

• Epigenetic changes, including global hypomethylation and specific gene methylation alterations, are observed in women with PCOS.
• These epigenetic changes affect genes involved in hormonal regulation, inflammation, and metabolism.
• Disruptions in circadian clock gene expression are noted in women with PCOS, correlating with sleep disorders.

Conclusions:

• Epigenetic modifications and circadian rhythm disruptions are potential key players in PCOS pathogenesis.
• Distinguishing cause from consequence remains a challenge for epigenetic biomarkers.
• Targeting epigenetic modifications offers potential for precision medicine approaches in PCOS management, pending further research in large cohorts.