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N-乙酰半胱氨酸和左旋肉碱可预防由轻度子宫内膜异位症不孕女性的卵泡液引起的卵母细胞减数分裂损伤。

N-Acetyl-Cysteine and l-Carnitine Prevent Meiotic Oocyte Damage Induced by Follicular Fluid From Infertile Women With Mild Endometriosis.

机构信息

Human Reproduction Division, Department of Gynecology and Obstetrics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

Department of Genetics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.

出版信息

Reprod Sci. 2016 Mar;23(3):342-51. doi: 10.1177/1933719115602772. Epub 2015 Sep 3.

Abstract

This study evaluated the potential protective effect of the antioxidants, l-carnitine (LC) and N-acetyl-cysteine (NAC), in preventing meiotic oocyte damage induced by follicular fluid (FF) from infertile women with mild endometriosis (ME). We performed an experimental study. The FF samples were obtained from 22 infertile women undergoing stimulated cycles for intracytoplasmic sperm injection (11 with ME and 11 without endometriosis). Immature bovine oocytes were submitted to in vitro maturation (IVM) divided into 9 groups: no-FF (No-FF); with FF from control (CFF) or ME (EFF) groups; and with LC (C + LC and E + LC), NAC (C + NAC and E + NAC), or both antioxidants (C + 2Ao and E + 2Ao). After IVM, oocytes were immunostained for visualization of microtubules and chromatin by confocal microscopy. The percentage of meiotically normal metaphase II (MII) oocytes was significantly lower in the EFF group (51.35%) compared to No-FF (86.36%) and CFF (83.52%) groups. The E + NAC (62.22%), E + LC (80.61%), and E + 2Ao (61.40%) groups showed higher percentage of normal MII than EFF group. The E + LC group showed higher percentage of normal MII than E + NAC and E + 2Ao groups and a similar percentage to No-FF and CFF groups. Therefore, FF from infertile women with ME causes meiotic abnormalities in bovine oocytes, and, for the first time, we demonstrated that the use of NAC and LC prevents these damages. Our findings elucidate part of the pathogenic mechanisms involved in infertility associated with ME and open perspectives for further studies investigating whether the use of LC could improve the natural fertility and/or the results of in vitro fertilization of women with ME.

摘要

本研究评估了抗氧化剂左旋肉碱(LC)和 N-乙酰半胱氨酸(NAC)在预防轻度子宫内膜异位症(ME)不孕患者卵泡液(FF)引起的卵母细胞减数分裂损伤中的潜在保护作用。我们进行了一项实验研究。FF 样本取自 22 名接受体外受精(ICSI)刺激周期的不孕女性(11 名 ME,11 名无子宫内膜异位症)。不成熟的牛卵母细胞进行体外成熟(IVM),分为 9 组:无 FF(No-FF);有对照(CFF)或 ME(EFF)组的 FF;有 LC(C + LC 和 E + LC)、NAC(C + NAC 和 E + NAC)或两种抗氧化剂(C + 2Ao 和 E + 2Ao)。IVM 后,通过共聚焦显微镜对卵母细胞进行微管和染色质的免疫染色。与 No-FF(86.36%)和 CFF(83.52%)组相比,EFF 组的中期 II(MII)卵母细胞减数分裂正常的比例显著降低(51.35%)。E + NAC(62.22%)、E + LC(80.61%)和 E + 2Ao(61.40%)组的正常 MII 比例高于 EFF 组。E + LC 组的正常 MII 比例高于 E + NAC 和 E + 2Ao 组,与 No-FF 和 CFF 组相似。因此,ME 不孕女性的 FF 导致牛卵母细胞减数分裂异常,并且我们首次证明 NAC 和 LC 的使用可预防这些损伤。我们的研究结果阐明了与 ME 相关的不孕的部分发病机制,并为进一步研究左旋肉碱是否可以改善 ME 女性的自然生育力和/或体外受精的结果提供了新的视角。

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