控制性卵巢刺激对多囊卵巢综合征患者和正常排卵妇女卵源性因子表达的差异

Different Effects of Controlled Ovarian Simulation on Expression of GDF9 and BMP15 from Normal Ovulatory Women and Women with PCOS

【目的】研究控制性卵巢刺激对多囊卵巢综合征(PCOS)患者和正常排卵妇女卵母细胞和颗粒细胞中卵源性因子(生长分化因子GDF9和骨形成蛋白BMP15)表达的影响及两组妇女之间的表达差异。【方法】收集PCOS患者和正常排卵的不孕妇女共97例,分为4组:22例未经历卵巢刺激(未刺激-PCOS组)和18例经历卵巢刺激(刺激-PCOS组)的PCOS患者,28例未经历卵巢刺激(未刺激-对照组)和29例经历卵巢刺激(刺激-对照组)的正常排卵妇女。收集4组患者的卵母细胞和颗粒细胞,采用巢式实时定量PCR的方法检测两种细胞中GDF9和BMP15 mRNA的表达水平。【结果】在正常排卵妇女的卵母细胞中,GDF9和BMP15 mRNA的表达水平在未刺激组分别为24.79(2.96-109.73)和0.93(0.05-3.65),在卵巢刺激组分别为149.94(55.38-387.93)和41.65(6.50-96.11),两种因子在卵巢刺激组的表达水平均显著高于未刺激组,差异有统计学意义(P<0.05)。在正常排卵妇女的颗粒细胞中,GDF9和BMP15 mRNA的表达水平在未刺激组分别为0.02(0.009-0.21)和0.008(0.001-0.16),在卵巢刺激组分别为0.10(0.06,0.18)和0.02(0.01-0.03),两种因子在卵巢刺激组的表达水平均显著高于未刺激组,差异有统计学意义(P<0.05)。在PCOS患者的卵母细胞中,GDF9和BMP15 mRNA的表达水平在未刺激组分别为23.83(2.29-65.72)和0.09(0.05-29.32),在卵巢刺激组分别为44.81(5.93-489.19)和0.10(0.05-11.44),两种因子的表达在未刺激组和卵巢刺激组均没有差异(P>0.05)。在PCOS患者的颗粒细胞中,GDF9和BMP15 mRNA的表达水平在未刺激组分别为0.11(0.06,0.16)和0.000 005(0.000 004 8-0.000 009),在卵巢刺激组分别为0.05(0.03,0.09)和0.02(0.007-0.03),GDF9 mRNA的表达在卵巢刺激组显著低于未刺激组,而BMP15 mRNA的表达在卵巢刺激组显著高于未刺激组,差异均有统计学意义(P<0.05)。【结论】控制性卵巢刺激可以促进正常排卵妇女卵母细胞和颗粒细胞中GDF9和BMP15的表达,但是对PCOS患者卵母细胞中两种因子的表达没有促进作用,提示PCOS患者卵母细胞中卵源性因子的表达对卵巢刺激的反应性受到抑制,可能影响卵泡发育和卵母细胞成熟,从而导致卵母细胞质量低下。

[Objective] To study the effects of COS on the expression of GDF9 and BMP15 in oocytes and granulosa cells from normal ovulation women and women with PCOS,and explore the differences between the two groups.[Methods] The study comprised four groups of patients：PCOS patients with COS （stimulated-PCOS） and without COS （unstimulated-PCOS）,normal ovulatory women with COS （stimulated-control） and without COS （unstimulated-control）.Oocytes and granulosa cells were collected from four groups of patients and the nest real-time quantitative PCR was used to detect the abundance of GDF9 and BMP15 mRNA.[Results] In oocytes from normal ovulatory women,the expression levels of GDF9 and BMP15 mRNA were 24.79 （2.96-109.73） and 0.93 （0.05-3.65） respectively in the unstimulated group.The results were 149.94 （55.38-387.93） and 41.65 （6.50-96.11） respectively in the stimulated group.The expression levels of the two factors in the stimulated group were significantly higher than that in the unstimulated group （P 〈 0.05）.In granulosa ceils from normal ovulatory women,the expression levels of GDF9 and BMP15 mRNA were 0.02（0.009,0.21） and 0.008 （0.001-0.16） respectively in the unstimulated group.The results were 0.10 （0.06,0.18） and 0.02 （0.01-0.03） respectively in the stimulated group.The expression levels of the two factors in the stimulated group were also significantly higher than that in the unstimulated group （P 〈0.05）.In oocytes from PCOS patients,the expression levels of GDF9 and BMP15 mRNA were 23.83 （2.29-65.72） and 0.09 （0.05-29.32） respectively in the unstimulated group.The results were 44.81 （5.93-489.19） and 0.10 （0.05-11.44） respectively in the stimulated group.There were no significant differences between the two groups （P 〉 0.05）.In granulosa cells from PCOS patients,the expression levels of GDF9 and BMP15 mRNA were 0.11 （0.06,0.16） and 0.000 005 （0.000 004 8-0.000 009） respectively in the unstimulated group.The results were 0.05 （0.03,0.09） and 0.02 （0.007-0.03） respectively in the stimulated group.The expression level of GDF9 mRNA was significantly lower in the stimulated group than that in the unstimulated group （P 〈 0.05）,while the expression level of BMP15 mRNA was significantly higher in the stimulated group than that in the unstimulated group （P 〈 0.05）.[Conclusion] The controlled ovarian stimulation can promote the expression of GDF9 and BMP15 both in oocytes and GCs from normal ovulatory women.However,the stimulating effects may be inhibited in oocytes from PCOS patients,which subsequently impair cytoplasm maturation and lead to poor oocyte quality.