Cadmium Exposure in Male Rats Results in Ovarian Granulosa Cell Apoptosis in Female Offspring and Paternal Genetic Effects

IF 4.4 3区 医学 Q2 ENVIRONMENTAL SCIENCES Environmental Toxicology Pub Date : 2024-08-09 DOI:10.1002/tox.24375
Qingyu Li, Yuchen Li, Jianlin Zhu, Zhangpin Liu, Yi Sun, Yake Lv, Jingwen Li, Lingfeng Luo, Chenyun Zhang, Wenchang Zhang
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Abstract

The aim of this study was to investigate whether the damage to male offspring induced by cadmium (Cd) exposure during embryonic period leads to the apoptosis of ovarian granulosa cells (OGCs) in the next generation of female offspring, and whether this apoptosis in the offspring was due to paternal genetic effects. Pregnant Sprague–Dawley (SD) rats were exposed to CdCl2 (0, 0.5, 2.0, or 8.0 mg/kg) by gavage daily for 20 days to produce the filial 1 (F1) generation. F1 males were mated with newly purchased females to produce the F2 generation, and the F3 generation was generated in the same way. No apoptotic bodies were observed in the OGCs of either the F2 or F3 generation as shown by electron microscopy, and a reduced OGC apoptosis rate (detected by flow cytometry) was observed in F2 OGCs from the Cd-exposed group. Moreover, the mRNA (qRT-PCR) levels of Bax and Bcl-2 and the protein (western blotting) level of pro-caspase-8 increased in the F2 generation (p < 0.05). The expression of apoptosis-related miRNAs (qRT-PCR) and methylation of apoptosis-related genes (determined via bisulfite-sequencing PCR) in OGCs were further determined. Compared with those of the controls, the expression patterns of microRNAs (miRNAs) in the F2 offspring were different in the Cd-exposed group. The miR-92a-2-5p expression levels were decreased in both the F2 and F3 generations (p < 0.05), while the average methylation level of apoptosis-related genes did not change significantly (except for individual loci). In summary, this study showed that the paternal genetic intergenerational effect of male Cd exposure during embryonic period induced apoptosis of OGCs in the offspring was weakened, and the transgenerational effect disappeared; nevertheless, intergenerational and transgenerational changes in apoptosis-related genes, epigenetic modifications, DNA methylation, and miRNAs were observed, and may be important for understanding the homeostatic mechanisms of the body to alleviate the intergenerational transmission of Cd-induced damage.

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雄性大鼠暴露于镉会导致雌性后代卵巢颗粒细胞凋亡和父系遗传效应。
本研究旨在探讨胚胎期镉(Cd)暴露对雄性后代的损伤是否会导致下一代雌性后代卵巢颗粒细胞(OGCs)的凋亡,以及这种凋亡是否是由于父系遗传效应所致。怀孕的Sprague-Dawley(SD)大鼠每天灌胃接触氯化镉(0、0.5、2.0或8.0毫克/千克)20天,以产生孝子1代(F1)。F1 雄性与新购买的雌性交配产生 F2 代,F3 代以同样的方法产生。电子显微镜显示,F2 代或 F3 代的 OGC 中均未观察到凋亡体,而在 Cd 暴露组的 F2 OGC 中,观察到 OGC 的凋亡率降低(通过流式细胞仪检测)。此外,在 F2 代中,Bax 和 Bcl-2 的 mRNA(qRT-PCR)水平以及 pro-caspase-8 的蛋白质(Western 印迹)水平都有所提高(p<0.05)。
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来源期刊
Environmental Toxicology
Environmental Toxicology 环境科学-毒理学
CiteScore
7.10
自引率
8.90%
发文量
261
审稿时长
4.5 months
期刊介绍: The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are: Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration; Natural toxins and their impacts; Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation; Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard; Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.
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