Context: Polycystic ovary syndrome (PCOS) represents the commonest endocrine abnormality in women of reproductive age. The cause of PCOS remains largely unknown, but studies suggest an intrinsic ovarian abnormality.

Objective: To test our hypothesis that differences in granulosa cell proliferation and apoptosis may underlie abnormalities that affect follicular development.

Design: Granulosa cells were prepared from follicular fluid aspirated from 4-8 mm follicles of unstimulated ovaries during routine laparoscopy or laparotomy from women with anovulatory PCOS and those with regular ovulatory cycles.

Setting: University hospital.

Patients: 14 women with anovulatory PCOS and 9 women with regular ovulatory cycles.

Main outcome measures: Immunocytochemistry on granulosa cells to investigate apoptotic and proliferation rates, together with real-time RT-PCR to analyze gene expression profiles of apoptotic regulators.

Results: Significantly lower apoptotic rates were found in granulosa cells from patients with PCOS compared to women with regular ovulatory cycles (P = 0.004). Lower apoptotic rates were associated with decreased levels of the apoptotic effector caspase 3 (P = 0.001) and increased levels of the anti-apoptotic survival factor cIAP-2 in the PCOS group that were coupled to higher proliferation rates (P = 0.032). Gene expression profiling confirmed the immunocytochemical findings.

Conclusions: Our findings indicate that there are significant differences in the rate of cell death and proliferation in granulosa cell populations in PCOS patients. These are associated with decreased expression of apoptotic effectors and increased expression of a cell survival factor. These results provide new insights that may be useful in developing specific therapeutic intervention strategies in PCOS.