Yang Seung Chel, Yu Eun Jeong, Park Jae Kyun, Kim Tae Hyung, Eum Jin Hee, Paek Soo Kyung, Hwang Ji Young, Lyu Sang Woo, Kim Jin Young, Lee Woo Sik, Yoon Tae Ki, Song Haengseok, Lee Hee Jun
Department of Biomedical Science, CHA University, Seongnam-si, Gyeonggi-do, 13488, Korea.
Department of Obstetrics & Gynecology, Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul, Korea.
Reprod Sci. 2021 Sep;28(9):2495-2502. doi: 10.1007/s43032-021-00532-3. Epub 2021 Mar 10.
Previous studies have reported that the mitochondrial DNA (mtDNA) contents of cumulus cells (CCs) in ovarian follicular fluid are correlated with embryo quality. Quantification of mtDNA CCs has been suggested as a biomarker of embryo viability. The aim of this study was to determine the relationship between mitochondrial DNA (mtDNA)/genomic DNA (gDNA) ratio in CCs and IVF outcomes such as fertilization rates and embryo quality in infertile women. This is an observational study on 144 cumulus-oocyte complexes obtained from 144 patients undergoing IVF-intracytoplasmic sperm injection (ICSI) at a single fertility center. The CCs in ovarian follicular fluid from patients undergoing IVF-ICSI were collected by ovum pick-up. A relative copy number quantification was used to determine mtDNA/gDNA ratio. Quantitative real-time PCR for various markers (β2M and mtMinArc gene) was used to determine average mtDNA/gDNA ratio of CCs. Investigation of the correlation between mtDNA/gDNA ratio in CCs and IVF outcomes showed no statistically significant correlation between the mtDNA/gDNA ratio in CCs and fertilization rates. However, mtDNA/gDNA ratio and embryo quality showed a statistically significant positive correlation. A significantly higher mtDNA/gDNA ratio was observed in the good quality embryo group compared with the poor quality embryo group (P < 0.05). In addition, the mtDNA/gDNA ratio showed negative correlation with the patient's age (correlation coefficient= -0.228, P < 0.05). Results of this study demonstrate a negative correlation of mtDNA/gDNA ratio in CCs with patient's age, and a low copy number of mtDNA in CCs may have adverse effects on embryo quality in IVF cycles. These results suggest that the ratio of mtDNA/gDNA in CCs may serve as a biomarker in predicting IVF outcomes.
以往研究报道,卵巢卵泡液中卵丘细胞(CCs)的线粒体DNA(mtDNA)含量与胚胎质量相关。mtDNA CCs的定量分析已被提议作为胚胎活力的生物标志物。本研究的目的是确定CCs中线粒体DNA(mtDNA)/基因组DNA(gDNA)比值与不孕女性体外受精(IVF)结果(如受精率和胚胎质量)之间的关系。这是一项对从单个生育中心接受IVF-卵胞浆内单精子注射(ICSI)的144例患者获取的144个卵丘-卵母细胞复合体进行的观察性研究。通过取卵收集接受IVF-ICSI患者卵巢卵泡液中的CCs。采用相对拷贝数定量法测定mtDNA/gDNA比值。使用针对各种标志物(β2M和mtMinArc基因)的定量实时PCR来测定CCs的平均mtDNA/gDNA比值。对CCs中mtDNA/gDNA比值与IVF结果之间的相关性进行研究,结果显示CCs中mtDNA/gDNA比值与受精率之间无统计学显著相关性。然而,mtDNA/gDNA比值与胚胎质量呈统计学显著正相关。与质量差的胚胎组相比,质量好的胚胎组中观察到mtDNA/gDNA比值显著更高(P < 0.05)。此外,mtDNA/gDNA比值与患者年龄呈负相关(相关系数 = -0.228,P < 0.05)。本研究结果表明CCs中mtDNA/gDNA比值与患者年龄呈负相关,且CCs中mtDNA拷贝数低可能对IVF周期中的胚胎质量产生不利影响。这些结果表明,CCs中mtDNA/gDNA比值可作为预测IVF结果的生物标志物。