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 in utero 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 CYP19 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 CYP19 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 ESR1 and ESR2 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.

中文翻译：

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胎儿编程：在子宫内接触丙烯酰胺会导致代际间卵巢功能受损并加速卵巢衰老

在这项研究中，我们调查了多代接触丙烯酰胺 (ACR) 对卵巢功能的影响。50 天大的 Wistar 白化雌性大鼠从怀孕第 6 天到分娩分为对照组和 ACR 治疗组（2.5、10 和 20 mg/kg/天）。获得的第一代（AF1）和第二代（AF2）雌性在4周龄时被安乐死，并收集血浆和卵巢样本。我们发现在子宫内多代接触 ACR 通过诱导组织病理学变化降低 AF1 的生育能力和卵巢功能，表现为囊肿和退化卵泡的出现、卵母细胞空泡化和颗粒细胞固缩。TUNEL法证实的TMR红阳性细胞主要在治疗组的基质中检测到。由于CYP19基因及其蛋白表达减少，雌二醇和 IGF-1 浓度显着降低。然而，与对照组相比，所有治疗组的高雌二醇和黄体酮水平证明了 AF2 中 ACR 暴露导致卵巢早衰，对应于CYP19的上调基因和蛋白质表达。与对照组相比，大量检测到基质的凋亡细胞，而ESR1和ESR2基因表达无显着差异。这项研究证实了 ACR 对至少连续两代人的卵巢功能和生育能力的发育不良影响。它强调在怀孕期间需要采取更有效的策略，例如吃健康食品和避免食用富含 ACR 的产品，包括油炸食品和咖啡。