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孕期接触丙烯酰胺会对两代雌性后代的性别比例、芳香酶和细胞凋亡产生不同的影响。

Prenatal exposure to acrylamide differently affected the sex ratio, aromatase and apoptosis in female adult offspring of two subsequent generations.

机构信息

Department of Pathology, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia; Department of Zoology, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.

出版信息

Physiol Res. 2023 Mar 8;72(1):59-69. doi: 10.33549/physiolres.934975. Epub 2022 Dec 22.

DOI:10.33549/physiolres.934975
PMID:36545876
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10069810/
Abstract

In the present study, we investigated the effect of acrylamide (ACR) exposure during pregnancy on the ovary of female adult offspring of two subsequent generations. Sixty-day-old Wistar albino female rats were given different doses of ACR (2.5 and 10 mg/kg/day) from day 6 of pregnancy until giving birth. Females from the first generation (AF1) were fed ad libitum, and thereafter, a subgroup was euthanized at 8 weeks of age and ovary samples were obtained. The remaining females were maintained until they reached sexual maturity (50 days old) and then treated in the same way as the previous generation to obtain the second generation of females (AF2). The histopathological examination indicated a high frequency of corpora lutea along with an increased number of antral follicles that reached the selectable stage mainly at a dose of 2.5 mg/kg/day. Interestingly, ACR exposure significantly increased the mRNA levels of CYP19 gene and its corresponding CYP19 protein expression in AF1 females. The TUNEL assay showed a significantly high rate of apoptosis in stromal cells except for dose of 2.5 mg/kg/day. However, in AF2 females, ACR exposure significantly increased the number of degenerating follicles and cysts while the number of growing follicles was reduced. Moreover, in both ACR-treated groups, estradiol-producing enzyme CYP19A gene and its corresponding protein were significantly reduced, and an excessive apoptosis was produced. We concluded that the ovarian condition of AF1 females had considerable similarity to the typical early perimenopausal stage, whereas that of AF2 females was similar to the late perimenopausal stage in women.

摘要

在本研究中,我们研究了孕期丙烯酰胺(ACR)暴露对两代雌性后代成年卵巢的影响。60 日龄 Wistar 白化雌性大鼠从怀孕第 6 天开始每天给予不同剂量的 ACR(2.5 和 10mg/kg)直至分娩。第一代雌性(AF1)自由进食,然后亚组在 8 周龄时安乐死并获取卵巢样本。其余雌性继续饲养直至性成熟(50 天龄),然后以与前一代相同的方式处理以获得第二代雌性(AF2)。组织病理学检查表明,黄体数量较高,同时有较多的窦前卵泡达到可选择阶段,主要在 2.5mg/kg/day 剂量下。有趣的是,ACR 暴露显著增加了 AF1 雌性中 CYP19 基因的 mRNA 水平及其相应的 CYP19 蛋白表达。TUNEL 检测显示基质细胞的凋亡率显著升高,但 2.5mg/kg/day 剂量除外。然而,在 AF2 雌性中,ACR 暴露显著增加了退化卵泡和囊肿的数量,而生长卵泡的数量减少。此外,在两个 ACR 处理组中,雌激素产生酶 CYP19A 基因及其相应蛋白均显著降低,并且产生了过度凋亡。我们得出结论,AF1 雌性的卵巢状况与典型的早绝经前期相当,而 AF2 雌性的卵巢状况与女性的晚绝经后期相似。

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