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异维 A 酸(视黄酸)暴露致雌性 Sprague-Dawley 大鼠卵巢储备功能下降。

Decreased ovarian reserve in female Sprague-Dawley rats induced by isotretinoin (retinoic acid) exposure.

机构信息

Namik Kemal University, Faculty of Medicine, Department of Gynecology and Obstetrics, Tekirdag, Turkey.

出版信息

Reprod Biomed Online. 2013 Aug;27(2):184-91. doi: 10.1016/j.rbmo.2013.04.010. Epub 2013 May 4.

DOI:10.1016/j.rbmo.2013.04.010
PMID:23768617
Abstract

Isotretinoin is a retinoid widely used for the treatment of severe nodulocystic acne. Although it has broad side effects, there is no well-designed study about its effects on the ovary. This study investigated possible toxic effects of isotretinoin on female gonads. A total of 30 female rats were randomly divided into three equal groups according to the dose of isotretinoin they were administered: 0 mg/kg/day (group 1), 7.5 mg/kg/day (group 2) or 15 mg/kg/day (group 3). Thirty days after the treatment, the effects of isotretinoin on the ovaries were evaluated with serum anti-Müllerian hormone (AMH) concentrations, apoptosis by TUNEL assay and immunohistochemical observations by proliferating cell nuclear antigen (PCNA). The percentage of atretic follicles was calculated for each stage of folliculogenesis. The serum AMH concentrations were found to be lower in both isotretinoin groups. The percentage of atretic follicles in both isotretinoin groups was higher than the control. The number of PCNA-positive granulosa cells was decreased in the isotretinoin groups. The number of ovarian follicles with apoptotic granulosa cells was increased in the experimental groups. These data are the first to identify that exposure of isotretinoin may be responsible for decreased ovarian reserve and toxic effects on rat ovaries.

摘要

异维 A 酸是一种广泛用于治疗严重结节性囊肿性痤疮的维甲酸。尽管它有广泛的副作用,但没有关于它对卵巢影响的精心设计的研究。本研究旨在探讨异维 A 酸对女性性腺的可能毒性作用。将 30 只雌性大鼠随机分为三组,根据给予的异维 A 酸剂量分为:0mg/kg/天(第 1 组)、7.5mg/kg/天(第 2 组)或 15mg/kg/天(第 3 组)。治疗 30 天后,通过血清抗苗勒管激素(AMH)浓度、TUNEL 检测法评估异维 A 酸对卵巢的影响,以及通过增殖细胞核抗原(PCNA)进行免疫组织化学观察。计算每个卵泡发生阶段的闭锁卵泡百分比。发现两组异维 A 酸组的血清 AMH 浓度均较低。两组异维 A 酸组的闭锁卵泡百分比均高于对照组。异维 A 酸组的颗粒细胞 PCNA 阳性细胞数减少。实验组卵巢卵泡中凋亡的颗粒细胞数量增加。这些数据首次表明,异维 A 酸的暴露可能导致卵巢储备减少和对大鼠卵巢的毒性作用。

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