Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, China; Centre of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, China.
Centre of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, China.
Reprod Biomed Online. 2019 Feb;38(2):152-158. doi: 10.1016/j.rbmo.2018.10.011. Epub 2018 Dec 14.
Is low MFN2 expression associated with ageing in granulosa cells as well as assisted reproductive technology (ART) outcome, and what is the underlying mechanism of action of MFN2?
In a prospective study, fresh granulosa cells were obtained from 161 women aged 20-40 years who underwent IVF with embryo transfer and who were divided into two groups: the diminished ovarian reserve (DOR) group (n = 51) and the control group (n = 110). Patient characteristics including age, infertility duration, body mass index, FSH, anti-Müllerian hormone (AMH), antral follicle count (AFC) and husband's semen parameters and granulosa cell MFN2 expression levels, cell apoptosis, mitochondrial membrane potential (ΔΨm) and ATP levels were analysed.
There were no significant differences between the DOR and control groups in terms of age, infertility duration and husband'' semen parameters; however, significant (P< 0.05) changes were found between the two groups in FSH, AMH and AFC levels. MFN2 expression was remarkably lower in granulosa cells from the DOR group and decreased in both groups as age increased. Furthermore, among young patients, MFN2 levels significantly increased in patients with pregnancy. MFN2 protein levels and cell apoptosis were lower in the MFN2 knockdown (MFN2-siRNA) group than in the control (Cy3-siRNA) group. ΔΨm and ATP levels were reduced in the MFN2-siRNA group compared with the Cy3-siRNA group.
Low MFN2 expression levels in granulosa cells were related to ageing, which may be involved in the clinical outcome of ART by promoting cell apoptosis and affecting mitochondrial function.
低 MFN2 表达是否与颗粒细胞老化以及辅助生殖技术(ART)结局相关,以及 MFN2 的作用机制是什么?
在一项前瞻性研究中,从 161 名年龄在 20-40 岁之间接受体外受精胚胎移植的女性中获得新鲜的颗粒细胞,并将其分为两组:卵巢储备减少(DOR)组(n=51)和对照组(n=110)。分析患者特征,包括年龄、不孕持续时间、体重指数、FSH、抗苗勒管激素(AMH)、窦卵泡计数(AFC)和丈夫精液参数以及颗粒细胞 MFN2 表达水平、细胞凋亡、线粒体膜电位(ΔΨm)和 ATP 水平。
DOR 组和对照组在年龄、不孕持续时间和丈夫精液参数方面无显著差异;然而,两组之间在 FSH、AMH 和 AFC 水平上存在显著差异(P<0.05)。DOR 组颗粒细胞中 MFN2 表达明显降低,且两组随年龄增长而降低。此外,在年轻患者中,妊娠患者的 MFN2 水平显著升高。与对照组(Cy3-siRNA)相比,MFN2 敲低(MFN2-siRNA)组的 MFN2 蛋白水平和细胞凋亡均较低。与 Cy3-siRNA 组相比,MFN2-siRNA 组的 ΔΨm 和 ATP 水平降低。
颗粒细胞中低 MFN2 表达水平与衰老有关,可能通过促进细胞凋亡和影响线粒体功能,参与 ART 的临床结局。