Ben-Rafael Z, Varello M A, Meloni F, Fateh M, Mastroianni L, Flickinger G L
Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia 19104.
J Clin Endocrinol Metab. 1987 Oct;65(4):602-5. doi: 10.1210/jcem-65-4-602.
We measured the mitotic activity of granulosa cells, sex steroid concentrations in follicular fluids, and the maturity and fertilizability of oocytes from 49 follicles. Flow cytometric measurements of DNA were used to determine the percentage of cells in G0/G1, S, and G2/M phases of the cell cycle. Mitotic index was designated as the percentage of granulosa cells in S + G2/M. The progesterone concentration and the progesterone to estradiol ratio in follicular fluids were inversely correlated to mitotic index (r = -0.506; P less than 0.001, and r = -0.320; P less than 0.02, respectively). Estradiol and androstenedione levels did not correlate with the mitotic index. The mitotic index was higher in follicles with immature oocytes [25.6 +/- 2.0% (+/- SE); n = 7] than in follicles with mature oocytes (15.6 +/- 1.2%; n = 41; P less than 0.001). The mitotic index of granulosa cells was lowest in follicles with oocytes that fertilized (15.5 +/- 1.8%), higher in follicles with oocytes that remained unfertilized (18.5 +/- 1.3%; P less than 0.03), and highest in follicles with oocytes that fertilized abnormally (24.0 +/- 2.1%; P less than 0.02). Differences in maturity or fertilizability of oocytes were not associated with variations in follicular fluid progesterone concentrations. The study supports the concept that mitotic activity is decreased when granulosa cells become luteinized. During early follicular growth it is assumed that estradiol and perhaps androstenedione may be important regulators of cell division. Our findings suggest that progesterone, perhaps acting as an antiestradiol, is more important in controlling granulosa cell division of preovulatory follicles during the late follicular phase.
我们测量了49个卵泡颗粒细胞的有丝分裂活性、卵泡液中性类固醇浓度以及卵母细胞的成熟度和受精能力。采用流式细胞术检测DNA,以确定细胞周期中G0/G1、S和G2/M期的细胞百分比。有丝分裂指数定义为处于S + G2/M期的颗粒细胞百分比。卵泡液中的孕酮浓度以及孕酮与雌二醇的比值与有丝分裂指数呈负相关(分别为r = -0.506;P < 0.001,以及r = -0.320;P < 0.02)。雌二醇和雄烯二酮水平与有丝分裂指数无相关性。未成熟卵母细胞的卵泡有丝分裂指数较高[25.6 +/- 2.0%(+/-标准误);n = 7],而成熟卵母细胞的卵泡有丝分裂指数较低(15.6 +/- 1.2%;n = 41;P < 0.001)。受精卵母细胞的卵泡中颗粒细胞的有丝分裂指数最低(15.5 +/- 1.8%),未受精卵母细胞的卵泡中该指数较高(18.5 +/- 1.3%;P < 0.03),异常受精卵母细胞的卵泡中该指数最高(24.0 +/- 2.1%;P < 0.02)。卵母细胞成熟度或受精能力的差异与卵泡液孕酮浓度的变化无关。该研究支持这样的观点,即颗粒细胞黄体化时,有丝分裂活性降低。在卵泡早期生长过程中,推测雌二醇以及可能的雄烯二酮可能是细胞分裂的重要调节因子。我们的研究结果表明,孕酮可能作为一种抗雌激素,在卵泡晚期控制排卵前卵泡颗粒细胞分裂方面更为重要。