Instituto de Biología y Medicina Experimental-CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina.
Cell Biol Int. 2011 May;35(5):423-9. doi: 10.1042/CBI20100542.
PCOS (polycystic ovary syndrome) is a heterogeneous disease characterized by hyperandrogenaemia, hirsutism, oligo- or amenorrhea, insulin resistance and anovulation. The aim of the present study was to evaluate if the balance between the ovarian expression of Bax (proapoptotic protein) and Bcl-2 (antiapoptotic protein) is altered in a PCOS model developed in rats by DHEA (dehydroepiandrosterone) administration. In addition, the ovarian morphology and the circulating progesterone levels were evaluated. Histological studies confirmed the presence of follicular cysts, atretic follicles and the absence of corpora lutea in the ovaries from the PCOS group and a significant decrease in circulating progesterone levels. Immunohistochemical studies showed that the expression of Bcl-2 and Bax were mainly localized in granulosa cells of AFs (antral follicles) in both groups. Bax expression was greater in preantral and AFs from PCOS ovarian sections than in the controls. In contrast, intense Bcl-2 immunostaining was observed in the control AFs, while Bcl-2 protein was either absent in PFs (preantral follicles) or weakly expressed in AFs from PCOS rats. These results were partially confirmed by Western studies. Data revealed that the ovarian level of Bcl-2 protein was lower in PCOS than in the control and that there were no differences in Bax ovarian levels between groups. However, Bax/Bcl-2 ratio was significantly higher in PCOS group than in the control group. In conclusion, an increase in ovarian apoptosis through an imbalance among the Bcl-2 family members may be involved in the transformation of growing follicles in cystic follicles in the ovaries from DHEA-induced PCOS rats.
多囊卵巢综合征(PCOS)是一种异质性疾病,其特征为高雄激素血症、多毛症、少经或闭经、胰岛素抵抗和排卵障碍。本研究旨在评估脱氢表雄酮(DHEA)诱导的大鼠 PCOS 模型中卵巢 Bax(促凋亡蛋白)和 Bcl-2(抗凋亡蛋白)表达平衡是否改变。此外,还评估了卵巢形态和循环孕酮水平。组织学研究证实,PCOS 组卵巢中存在卵泡囊肿、闭锁卵泡,且无黄体,循环孕酮水平显著降低。免疫组织化学研究表明,Bcl-2 和 Bax 的表达主要定位于两组的窦前卵泡(AFs)颗粒细胞中。与对照组相比,PCOS 卵巢切片中的前腔卵泡和 AFs 中 Bax 的表达更高。相反,对照组的 AFs 中观察到强烈的 Bcl-2 免疫染色,而 PFs(前腔卵泡)中 Bcl-2 蛋白缺失或 PCOS 大鼠的 AFs 中 Bcl-2 蛋白表达较弱。Western 研究部分证实了这些结果。数据显示,PCOS 组卵巢 Bcl-2 蛋白水平低于对照组,两组间卵巢 Bax 水平无差异。然而,PCOS 组的 Bax/Bcl-2 比值明显高于对照组。总之,通过 Bcl-2 家族成员之间的失衡导致卵巢细胞凋亡增加,可能参与了 DHEA 诱导的 PCOS 大鼠卵巢中生长卵泡向囊性卵泡的转化。