Das M, Djahanbakhch O, Hacihanefioglu B, Saridogan E, Ikram M, Ghali L, Raveendran M, Storey A
Academic Department of Women's Health, Barts and The London, Queen Mary's School of Medicine, University of London, and Newham University Hospital National Health Service Trust, London, UK.
J Clin Endocrinol Metab. 2008 Mar;93(3):881-7. doi: 10.1210/jc.2007-1650. Epub 2007 Dec 11.
Polycystic ovary syndrome (PCOS) represents the most common endocrine abnormality in women of reproductive age. The cause of PCOS remains largely unknown, but studies suggest an intrinsic ovarian abnormality.
The objective of the study was to test our hypothesis that differences in granulosa cell proliferation and apoptosis may underlie abnormalities that affect follicular development.
Granulosa cells were prepared from follicular fluid aspirated from 4- to 8-mm follicles of unstimulated ovaries during routine laparoscopy or laparotomy from women with anovulatory PCOS and those with regular ovulatory cycles.
The study was conducted at a university hospital.
Fourteen women with anovulatory PCOS and nine women with regular ovulatory cycles participated in the study.
Immunocytochemistry on granulosa cells to investigate apoptotic and proliferation rates, together with real-time RT-PCR to analyze gene expression profiles of apoptotic regulators, was measured.
Significantly lower apoptotic rates were found in granulosa cells from patients with PCOS, compared with 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 cellular inhibitor of apoptosis proteins-2 in the PCOS group that were coupled to higher proliferation rates (P=0.032). Gene expression profiling confirmed the immunocytochemical findings.
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.
多囊卵巢综合征（PCOS）是育龄女性中最常见的内分泌异常疾病。PCOS的病因在很大程度上仍不清楚，但研究表明存在内在的卵巢异常。
本研究的目的是验证我们的假设，即颗粒细胞增殖和凋亡的差异可能是影响卵泡发育异常的基础。
在常规腹腔镜检查或剖腹手术期间，从未刺激卵巢中4至8毫米卵泡抽吸的卵泡液中制备颗粒细胞，这些卵泡来自无排卵PCOS患者和有规律排卵周期的女性。
该研究在一家大学医院进行。
14名无排卵PCOS患者和9名有规律排卵周期的女性参与了研究。
对颗粒细胞进行免疫细胞化学检测以研究凋亡率和增殖率，并通过实时逆转录聚合酶链反应分析凋亡调节因子的基因表达谱。
与有规律排卵周期的女性相比，PCOS患者颗粒细胞的凋亡率显著降低（P=0.004）。较低的凋亡率与凋亡效应因子半胱天冬酶-3水平降低相关（P=0.001），且PCOS组中抗凋亡存活因子凋亡蛋白抑制因子-2水平升高，这与较高的增殖率相关（P=0.032）。基因表达谱分析证实了免疫细胞化学的结果。
我们的研究结果表明，PCOS患者颗粒细胞群体的细胞死亡和增殖率存在显著差异。这些差异与凋亡效应因子表达降低和细胞存活因子表达增加有关。这些结果为开发PCOS的特定治疗干预策略提供了新的见解。
