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. Pregnant rats in the control group (0mg/kg) received water by gavage and in the experimental groups received cadmium chloride solution (8.0mg/kg body weight) by gavage during gestation periods (from gestation day 1 to 21). At postnatal day 56, vaginal smears were conducted to evaluate the stage of the estrous cycle, all female offspring were sacrificed after anesthesia and and ovarian granulosa cells were isolated from the F1 SD rats.The DNA samples from the ovarian granulosa cells in the control and 8.0mg/kg CdCl2 groups were sequenced,three biological replicates were sequenced for each group.