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

ABSTRACT: 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.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE127254 | GEO | 2022/02/01

REPOSITORIES: GEO

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Project description:The oocyteâs capacity to complete maturation, to succeed fertilization and to reach the blastocyst stage is what defines the oocyteâs competence. The oocyte acquires this competence working closely with somatic cells of the follicle. Cumulus and granulosa cells provided support for the oocyteâs development and conversely the oocyte influence follicular cell growth and differentiation. Existing studies support the idea that follicular-stimulated hormone and luteinizing hormone play an essential role in oocyte competence acquisition through protein kinase A (PKA) and protein kinase C (PKC) signalling in granulosa cells. Therefore, human-like granulosa cells (KGN) were treated with forskolin 10 Î¼M and phorbol 12-myristate 13-acetate 0.1 Î¼M for 24 hours in order to process a transcriptomic analysis of differentially express genes between treatment. Over 2000 genes were founded to be differentially express at cut-off fold change of 1.5 and a p-value of 0.05. Five major upstreams, EGF, TGFB1, VEGF, FGF2 and HGF were founded to play an important role in competence acquisition thought PKA and PKC signalling. Differentially expressed targeted genes of both signalling pathways were classified in seven major ovarian functions such as PTGS2, IL8 and IL6 in inflammation, STAR, CYP11A1, CYP19A1 in steroidogenesis, VEGFC, VEGFA, CXCR4 in angiogenesis, AREG, EGFR, SPRY2 in differentiation, BAX, BCL2L12, CASP1 in apoptosis, CCND1, CCNB1, CCNB2 in division and MMP1, MMP9, TIMP1 in ovulation. Taken together, the results of this study suggest that PKA and PKC signalling potentiate their effects in some functions such as inflammation and apoptosis while some others are more specific to one or the other protein kinase like differentiation, ovulation and angiogenesis that are thought to be more PKC-dependent in human granulosa cells. 8 samples were analysed, 4 controls compared to 4 Phorbol 12-myristate 13-acetate treatments (total of 4 replicates).

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

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