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接受体外受精的女性颗粒细胞和卵泡液的端粒长度及端粒酶活性

Telomere Length and Telomerase Activity of Granulosa Cells and Follicular Fluid in Women Undergoing In Vitro Fertilization.

作者信息

Péntek Sándor, Várnagy Ákos, Farkas Bálint, Mauchart Péter, Gödöny Krisztina, Varjas Tímea, Kőszegi Tamás, Kaltenecker Péter, Jakabfi-Csepregi Rita, Kovács Kálmán, Bódis József, Sulyok Endre

机构信息

National Laboratory on Human Reproduction, University of Pécs, 7622 Pécs, Hungary.

Department of Obstetrics and Gynecology, University of Pecs Medical School, 7624 Pécs, Hungary.

出版信息

Antioxidants (Basel). 2023 Feb 8;12(2):419. doi: 10.3390/antiox12020419.

Abstract

This study aimed to evaluate the interrelationship between telomere length, telomerase activity and oxidative DNA damage in patients undergoing in vitro fertilization (IVF). This single-center, observational clinical study comprised 102 unselected, consecutive patients with various infertility diagnoses. Granulosa cells (GCs) and follicular fluid (FF) were analyzed simultaneously for telomere functions and for the marker of oxidative DNA damage, 8-hydroxy-2-deoxyguanosine (8-OHdG). An Absolute Human Telomere Lengths Quantification qPCR Assay kit and Telomerase Activity Quantification qPCR Assay kit (Nucleotestbio, Budapest, Hungary), as well as an 8-OHdG ELISA kit (Abbexa Ltd., Cambridge, United Kingdom) were used for analyses. Similar telomere lengths were found in GCs and FF, however telomerase activity was markedly depressed, while 8-OHdG levels were markedly elevated in FF compared with those in GCs ( < 0.01). Telomere lengths were independent of telomerase activity both in GCs and FF. However, GC 8-OHdG was inversely related to telomerase activity in GCs and FF ( < 0.05). Importantly, 8-OHdG levels both in GCs and FF had significant negative impact on the number of the retrieved and MII oocytes ( < 0.01), whereas FF 8-OHdG was negatively related further to the number of fertilized oocytes and blastocysts ( < 0.01). In conclusion, we could not confirm the direct association of telomere function and reproductive potential. However, oxidative DNA damage, as mainly reflected by 8-OHdG, adversely affected early markers of IVF outcome and clinical pregnancies.

摘要

本研究旨在评估体外受精(IVF)患者端粒长度、端粒酶活性与氧化性DNA损伤之间的相互关系。这项单中心观察性临床研究纳入了102例未经筛选的连续不孕患者,诊断各异。同时对颗粒细胞(GCs)和卵泡液(FF)进行端粒功能及氧化性DNA损伤标志物8-羟基-2'-脱氧鸟苷(8-OHdG)的分析。使用绝对人类端粒长度定量qPCR检测试剂盒和端粒酶活性定量qPCR检测试剂盒(Nucleotestbio,匈牙利布达佩斯)以及8-OHdG ELISA试剂盒(Abbexa Ltd.,英国剑桥)进行分析。在GCs和FF中发现了相似的端粒长度,然而端粒酶活性明显降低,而与GCs相比,FF中的8-OHdG水平明显升高(<0.01)。GCs和FF中的端粒长度均与端粒酶活性无关。然而,GC中的8-OHdG与GCs和FF中的端粒酶活性呈负相关(<0.05)。重要的是,GCs和FF中的8-OHdG水平均对获取的MII期卵母细胞数量有显著负面影响(<0.01),而FF中的8-OHdG与受精的卵母细胞和囊胚数量进一步呈负相关(<0.01)。总之,我们无法证实端粒功能与生殖潜能之间的直接关联。然而,主要由8-OHdG反映的氧化性DNA损伤对IVF结局和临床妊娠的早期标志物产生了不利影响。

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