PER3 expression in granulosa cells of women with polycystic ovary syndrome: a potential role of the ovarian peripheral clock in infertility.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with infertility, metabolic dysfunction, and circadian rhythms disturbances, including delayed melatonin secretion. The human Period3 (PER3) plays an important role in regulating tissue-specific peripheral circadian clock. This suggests that the PER3 may be an important component of the ovarian circadian clock and could contribute to PCOS pathogenesis. METHODS AND RESULTS: At first, PCOS-related RNAseq studies retrieved from the GEO database and analyzed to find differential gene expression in PCOS datasets. In experimental step, follicular fluid and surrounding cumulus cells were collected from 16 PCOS patients and 12 healthy women. Isolated granulosa cells from follicular fluid were cultured in α-MEM supplemented with the addition of follicular fluid and harvested at 2-hour intervals over 12 h timepoints. PER3 gene expression was measured by real-time PCR. Melatonin and estrogen hormone concentrations in follicular fluid were measured using ELISA. Both RNA-seq and qPCR showed a significant increase in PER3 gene expression in PCOS patients compared to controls. Also, the normal oscillation patterns of PER3 were disrupted in PCOS patients. Melatonin and estrogen levels were significantly reduced in PCOS group. CONCLUSION: Our findings suggest that increased PER3 gene expression and disruption of its rhythmicity in granulosa cells appear to be associated with PCOS. This circadian disruption may contribute to changes in melatonin and estrogen levels, potentially contributing to the development of PCOS symptoms.