Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou, 310006, Zhejiang, China.
Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China.
J Assist Reprod Genet. 2022 Oct;39(10):2239-2247. doi: 10.1007/s10815-022-02599-6. Epub 2022 Aug 31.
The purpose of this study was to explore the association of expression of cystic fibrosis transmembrane conductance regulator (CFTR) in cumulus cells (CCs) from mature oocytes with oocyte quality and embryonic development.
A total of 338 infertile women who underwent ovarian stimulation cycle of oocyte retrieval in Zhejiang University School of Medicine were retrospectively enrolled in this study. The relative mRNA expression levels of CFTR, bone morphogenetic protein 15 (BMP15), and growth differentiation factor 9 (GDF9) in CCs were detected by qPCR technology. ROC curve was applied for the diagnosis of oocyte maturation. The serum levels of anti-Müllerian hormone (AMH), E, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and androstenedione were measured. Oocyte maturation rate, fertilization rate, cleavage rate, high-quality embryo formation rate, and implantation rate after embryo transfer were also determined.
The mRNA expression levels of CFTR in CCs were significantly increased in metaphase II (MII) oocytes compared to that in metaphase I (MI) or germinal vesicle (GV) oocytes. The ROC curve analysis illustrated that CFTR mRNA expression could efficiently discriminate MII oocytes from MI or GV oocytes (AUC = 0.954), and revealed that 0.695 RQU is the optimal cut-off value for diagnosis. So the cut-off value of 2 = 0.70 was used to divide the patients into two groups: low- (n = 114) and high-CFTR group (n = 224). The mRNA expression of CFTR in CCs was positively correlated with the antral follicular count (AFC), number of oocytes retrieved, number of MII oocytes, serum E level on hCG day, and BMP15 and GDF9 expression in CCs. Under continuous stimulation with the same dose of recombinant follicle-stimulating hormone (rFSH), the number of follicles, average recovered oocytes, recovered oocytes, MII oocytes, as well as the oocyte recovery rate, fertilization rate, oocyte cleavage rate, high-quality embryo formation rate, and implantation rate were decreased in patients with lower CFTR.
This study suggests that CFTR expression in CCs is associated with the developmental potential of human oocytes.
本研究旨在探讨成熟卵母细胞中囊性纤维化跨膜电导调节因子（CFTR）的表达与卵母细胞质量和胚胎发育的关系。
回顾性分析浙江大学医学院接受卵巢刺激取卵周期的 338 例不孕妇女的资料。采用 qPCR 技术检测 CCs 中 CFTR、骨形态发生蛋白 15（BMP15）和生长分化因子 9（GDF9）的相对 mRNA 表达水平。应用 ROC 曲线诊断卵母细胞成熟。检测血清抗苗勒管激素（AMH）、E、卵泡刺激素（FSH）、黄体生成素（LH）和雄烯二酮水平。还测定了卵母细胞成熟率、受精率、卵裂率、优质胚胎形成率和胚胎移植后的着床率。
与 MI 或 GV 卵母细胞相比，MII 卵母细胞中 CFTR 的 mRNA 表达水平显著增加。ROC 曲线分析表明，CFTR mRNA 表达可有效区分 MI 或 GV 卵母细胞与 MII 卵母细胞（AUC=0.954），且 0.695 RQU 为最佳截断值用于诊断。因此，使用 2=0.70 将患者分为低（n=114）和高-CFTR 组（n=224）。CCs 中 CFTR 的 mRNA 表达与窦卵泡计数（AFC）、获卵数、MII 卵母细胞数、HCG 日血清 E 水平以及 CCs 中 BMP15 和 GDF9 的表达呈正相关。在相同剂量重组卵泡刺激素（rFSH）的持续刺激下，低 CFTR 患者的卵泡数、平均回收卵数、回收卵数、MII 卵母细胞数以及卵母细胞回收率、受精率、卵裂率、优质胚胎形成率和着床率均降低。
本研究提示 CCs 中 CFTR 的表达与人类卵母细胞的发育潜能有关。
