Maternal cadmium exposure during pregnancy changes DNA methylation patterns in adult F1 rats ovarian granulosa cells.

Cadmium is a heavy metal pollutant and environmental endocrine disruptor. Studies have shown that cadmium exposure, whether it occurs in adulthood, in puberty or during the period from weaning to sexual maturity, can produce notable toxic effects on ovarian cells, especially ovarian granulosa cells. However, the effects of prenatal cadmium exposure on the morphology, function and its epigenetic mechanism of ovarian granulosa cells in offspring during adulthood have not been reported.In this study,the promoter methylation was assessed using MeDIP-Chip and Several methods were used to analyze the scanned genes, including the Gene Ontology Consortium tools, hierarchical clustering and KEGG pathway analysis.The results indicated that multiple signaling pathways, including apoptosis and hormone synthesis related pathways were affected,besides, some genes DNA methylation status of apoptosis and hormone synthesis pathways were changed.In summary, our results provide a scientific basis for subsequent analyses of cadmium-induced ovarian granulosa cell damage and its epigenetic mechanism.镉是一种重金属污染物，同时也是环境内分泌干扰物。研究表明，无论镉暴露发生于成年期、青春期还是断奶至性成熟阶段，均可对卵巢细胞，尤其是卵巢颗粒细胞产生显著毒性作用。然而，目前尚未见孕期镉暴露对成年后代卵巢颗粒细胞的形态、功能及其表观遗传机制产生影响的相关报道。本研究采用MeDIP-Chip技术检测启动子甲基化水平，并通过多种方法对扫描获得的基因进行分析，包括基因本体联合会（Gene Ontology Consortium）分析工具、层次聚类法以及KEGG通路分析。结果显示，细胞凋亡、激素合成相关通路等多条信号通路均受到影响，且细胞凋亡与激素合成通路中部分基因的DNA甲基化状态发生改变。综上，本研究结果为后续探究镉诱导的卵巢颗粒细胞损伤及其表观遗传机制提供了科学依据。