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卵泡液中游离线粒体DNA水平可作为小卵巢子宫内膜异位囊肿患者妊娠成功的生物标志物:一项病例对照研究。

The levels of follicular fluid cell-free mitochondrial DNA could serve as a biomarker for pregnancy success in patients with small ovarian endometriosis cysts: A case-control study.

作者信息

Huo Ping, Zhang Ning, Zhang Pingping, Wu Xiaohua

机构信息

Hebei Medical University, Shijiazhuang.

Department of Reproductive Genetics, Hebei General Hospital, Shijiazhuang.

出版信息

Medicine (Baltimore). 2020 Nov 25;99(48):e23348. doi: 10.1097/MD.0000000000023348.

Abstract

Ovarian endometriosis cyst (OEC) is caused by the growth of ectopic endometrium into the ovarian cortex, leading to disrupted ovarian cortical structures and infertility. Large OECs are usually surgically removed, and assisted reproductive technology (ART) is required for future pregnancy. The oocyte reserve and development of patients with small non-surgical OECs are unknown. In this study, we compared mitochondrial abnormality, ATPase and IF1 mRNA expression levels, and OXPHO complex proteins between OEC vs control mural granulosa cells (mGCs).OEC mGCs show fewer mitochondria per cell, a higher proportion of aberrant morphology, lower ATPase mRNA levels, higher IF1 mRNA levels, and impaired expression of 3 of the 5 critical proteins involved in the OXPHOS complex, compared with control mGCs. Cell-free mitochondrial DNA (cfmtDNA) levels are higher in the follicular fluid of patients with OEC and were inversely associated with the expression of mtDNA in mGCs and cumulus granulosa cells (cGCs).Taken together, this study indicates that small non-surgical OECs lead to poor quality of oocytes and subsequent embryos during ART compared with control, which was accompanied by mGC mitochondrial dysfunction. mGC and cGC mtDNA and FF cfmtDNA might serve as efficient biomarkers for the non-invasive prediction of pregnancy outcomes in patients with OEC undergoing ART.

摘要

卵巢子宫内膜异位囊肿(OEC)是由异位的子宫内膜生长到卵巢皮质中引起的,导致卵巢皮质结构破坏和不孕。大型OEC通常通过手术切除,未来怀孕需要辅助生殖技术(ART)。小型非手术OEC患者的卵母细胞储备和发育情况尚不清楚。在本研究中,我们比较了OEC与对照壁层颗粒细胞(mGCs)之间的线粒体异常、ATP酶和IF1 mRNA表达水平以及氧化磷酸化(OXPHOS)复合体蛋白。与对照mGCs相比,OEC mGCs每个细胞中的线粒体数量更少,异常形态的比例更高,ATP酶mRNA水平更低,IF1 mRNA水平更高,并且参与OXPHOS复合体的5种关键蛋白中有3种的表达受损。OEC患者卵泡液中的游离线粒体DNA(cfmtDNA)水平更高,并且与mGCs和卵丘颗粒细胞(cGCs)中线粒体DNA的表达呈负相关。综上所述,本研究表明,与对照相比,小型非手术OEC在ART期间会导致卵母细胞和后续胚胎质量较差,同时伴有mGC线粒体功能障碍。mGC和cGC的线粒体DNA以及卵泡液中的cfmtDNA可能作为接受ART的OEC患者妊娠结局非侵入性预测的有效生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd32/7710174/8533cd786e83/medi-99-e23348-g001.jpg

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