PCOS患者卵源性因子BMP6、BMP15、GDF9异常表达与颗粒细胞凋亡相关性

The abnormal expression of BMP6,BMP15 and GDF9 in Patients with PCOS and correlate to granulosa cell apoptosis

目的探讨PCOS患者卵泡液中骨形成蛋白BMP6、BMP15、GDF9的异常改变与颗粒细胞凋亡的相关性及对IVF结局的影响。方法将138例研究对象分为PCOS组与正常排卵组,对两组患者的临床及IVF批标进行对比分析,同时对两组患者的卵泡液行BMP6、BMP15、GDF9检测,且检测了两组颗粒细胞的Bcl-2及Caspase-3的表达情况,进而就卵液中的BMP6、BMP15、GDF9水平与颗粒细胞内的Bcl-2及Caspase-3表达量之间进行相关性分析。结果 PCOS组与对照组相比,患者的年龄、初潮年龄、Gn用量、获卵数、MⅡ卵率、受精率、优质胚胎率及临床妊娠率均无显著差别(P>0.05),而BMI指数及可移植胚胎率均小于对照组,且差异具有统计学意义(P<0.05)。PCOS组与对照组相比,患者卵丘颗粒细胞内Bcl-2 m RNA及蛋白水平显著降低,而Caspase-3m RNA及蛋白水平升高,且差异具有统计学意义(P<0.05)。卵泡液中卵源性蛋白BMP6、BMP15与颗粒细胞内凋亡调控因子Bcl-2有呈正相关,与Caspase-3呈负相关性(P<0.05)。GDF9与Caspase-3呈负相关性(P<0.05),与Bcl-2有一定相关性,但无统计学意义。结论 PCOS患者不仅卵泡液中存在BMP6、BMP15、GDF9的异常体变,且存在颗粒细胞内凋亡调控因子的异常改变,同时二者之间存在一定的相关性。

Objective：To investigate the potential effect of BMP6,BMP15 and GDF9 abnormal changes in follicular fluid on IVF outcome through the granulosa cell apoptosis. Methods：A total of 70 PCOS patients（PCOS group）and 68 female patients with normal ovarian function（control group）we collected. The general information,ages,retrieved oocyte number,BMI,Gn dosage,menarche age,fertilization rate,portable embryo rate,high-quality embryo rate,clinical pregnancy rate were recorded. Real-time PCR was used to detect the m RNA levels of Bcl-2 and Caspase-3 in the granulosa cell of all subjects. Western blotting was used to detect the expression of Bcl-2 and Caspase-3 in the granulosa cell and BMP6,BMP15 and GDF9 in the follicular fluid of all subjects. Results：Compared with control group,the BMI and portable embryo rate was significantly decreased（P〈0.05）,the other general information have no significant differences（P〉0.05）. The BMP6,BMP15 and GDF9 expression were significantly decreased in PCOS group compared with the control group（P〈0.05）. The m RNA and protein levels of Bcl-2 were significantly increased and the Caspase-3 was significantly decreased in PCOS group compared with the control group（P〈0.05）. The BMP6 and BMP15 were positively correlated with Bcl-2（P〈0.05）and negatively correlated with Caspase-3（P〈0.05）. GDF9 was has negative correlation with Caspase-3（P〈0.05）and has certain correlation with Bcl-2,but without statistical significance（P〈0.05）. Conclusions：From these data above we supposed that the low expression of BMP6,BMP15 and GDF9 may affect oocyte quality and embryo development potential and be correlated with the granulosa cell apoptosis.