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胎儿编程:丙烯酰胺暴露导致代际卵巢功能障碍和加速卵巢衰老。

Fetal programming: exposure to acrylamide leads to intergenerational disrupted ovarian function and accelerated ovarian aging.

机构信息

Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.

Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.

出版信息

Aging (Albany NY). 2022 Sep 6;14(17):6887-6904. doi: 10.18632/aging.204269.

DOI:10.18632/aging.204269
PMID:36069806
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9512500/
Abstract

In this study we investigated the effects of multigenerational exposures to acrylamide (ACR) on ovarian function. Fifty-day-old Wistar albino female rats were divided into the control and ACR-treated groups (2.5, 10, and 20 mg/kg/day) from day 6 of pregnancy until delivery. The obtained females of the first (AF1) and second generation (AF2) were euthanized at 4 weeks of age, and plasma and ovary samples were collected. We found that multigenerational exposure to ACR reduced fertility and ovarian function in AF1 through inducing histopathological changes as evidenced by the appearance of cysts and degenerating follicles, oocyte vacuolization, and pyknosis in granulosa cells. TMR red positive cells confirmed by TUNEL assay were mostly detected in the stroma of the treated groups. Estradiol and IGF-1 concentrations significantly decreased as a result of decreased gene and its protein expression. However, ACR exposure in AF2 led to early ovarian aging as evidenced by high estradiol and progesterone levels among all treated groups compared to control group, corresponding to the upregulation of the gene and protein expression. The apoptotic cells of the stroma were greatly detected compared to that in the control group, whereas no significant difference was reported in and gene expression. This study confirms the developmental adverse effects of ACR on ovarian function and fertility in at least two consecutive generations. It emphasizes the need for more effective strategies during pregnancy, such as eating healthy foods and avoiding consumption of ACR-rich products, including fried foods and coffee.

摘要

在这项研究中,我们调查了丙烯酰胺(ACR)多代暴露对卵巢功能的影响。从怀孕第 6 天到分娩,将 50 天大的 Wistar 白化雌性大鼠分为对照组和 ACR 处理组(2.5、10 和 20 mg/kg/天)。第一代(AF1)和第二代(AF2)获得的雌性大鼠在 4 周龄时被安乐死,并收集血浆和卵巢样本。我们发现,多代暴露于 ACR 通过诱导囊泡和退化卵泡、卵母细胞空泡化和颗粒细胞固缩等组织病理学变化,降低了 AF1 的生育力和卵巢功能。TUNEL 检测证实 TMR 红色阳性细胞主要存在于处理组的基质中。雌二醇和 IGF-1 浓度显著降低,导致基因及其蛋白表达减少。然而,在 AF2 中暴露于 ACR 导致卵巢早衰,与对照组相比,所有处理组的雌二醇和孕激素水平升高,与基因和蛋白表达上调相对应。与对照组相比,基质中的凋亡细胞明显增多,而和基因的表达没有明显差异。本研究证实 ACR 对卵巢功能和生育力的发育不良影响至少在两代连续中存在。它强调了在怀孕期间需要更有效的策略,例如食用健康食品和避免食用富含 ACR 的产品,包括油炸食品和咖啡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d8b/9512500/f89026855045/aging-14-204269-g007.jpg
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