Dataset Information

Gene expression in the fetal mouse ovary is altered by exposure to low doses of bisphenol A.

ABSTRACT: Evidence from experimental studies suggests that fetal exposure to the endocrine-disrupting chemical bisphenol A (BPA) has adverse reproductive effects in both males and females. Studies from our laboratory suggest that exposure to the developing female fetus produces a unique, multigenerational effect. Specifically, maternal exposure affects the earliest stages of oogenesis in the developing fetal ovary, and the resulting subtle meiotic defects increase the likelihood that embryos produced by the exposed female in adulthood (i.e., the grandchildren) will be chromosomally abnormal. To understand the impact of BPA on the developing ovary, we conducted expression studies to characterize gene expression changes in the fetal ovary that result from BPA exposure. We first tested the validity of the approach, asking whether we could reliably detect temporal changes in expression levels of meiotic genes in controls. As anticipated, we were able to identify appropriate increases in expression in meiotic, but in few other, genes. Intriguingly, this analysis provided data on a small set of genes for which timing and expression changes suggest that they may have important and heretofore unrecognized meiotic roles. After verifying the utility of our approach, we focused our analysis on BPA-exposed animals. We found modest, but significant, changes in gene expression in the fetal ovaries from exposed fetuses. The first changes were evident within 24 h of exposure, and the most extensive changes correlated with the onset of meiosis. Furthermore, gene ontology analysis suggested that BPA acts to down-regulate mitotic cell-cycle genes, raising the possibility that fetal BPA exposure may act to limit expansion of the primordial germ cell population.

SUBMITTER: Lawson C

PROVIDER: S-EPMC3012563 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Gene expression in the fetal mouse ovary is altered by exposure to low doses of bisphenol A.

Lawson Crystal C Gieske Mary M Murdoch Brenda B Ye Ping P Li Yunfei Y Hassold Terry T Hunt Patricia A PA

Biology of reproduction 20100825 1

Evidence from experimental studies suggests that fetal exposure to the endocrine-disrupting chemical bisphenol A (BPA) has adverse reproductive effects in both males and females. Studies from our laboratory suggest that exposure to the developing female fetus produces a unique, multigenerational effect. Specifically, maternal exposure affects the earliest stages of oogenesis in the developing fetal ovary, and the resulting subtle meiotic defects increase the likelihood that embryos produced by t ...[more]

PMID: 20739668

Similar Datasets

Project description:Genomic imprinting, a phenomenon by which genes are expressed in a monoallelic, parent-of-origin-dependent fashion, is critical for normal brain development. Expression of imprinted genes is regulated via epigenetic mechanisms, including DNA methylation (5-methylcytosine, 5mC), and disruptions in imprinting can lead to disease. Early-life exposure to the endocrine disrupting chemical bisphenol A (BPA) is associated with abnormalities in brain development and behavior, as well as with disruptions in epigenetic patterning, including 5mC and DNA hydroxymethylation (5-hydroxymethylcytosine, 5hmC). Using an established mouse model of perinatal environmental exposure, the objective of this study was to examine the effects of perinatal BPA exposure on epigenetic regulation of imprinted gene expression in adult mice. Two weeks prior to mating, dams were assigned to control chow or chow containing an environmentally relevant dose (50 µg/kg) of BPA. Exposure continued until offspring were weaned at post-natal day 21, and animals were followed until 10 months of age. Expression of three imprinted genes-Pde10a, Ppp1r9a, and Kcnq1, as well as three genes encoding proteins critical for regulation of 5mC and 5hmC-Dnmt1, Tet1, and Tet2, were evaluated in the right cortex and midbrain using qRT-PCR. Perinatal BPA exposure was associated with a significant increase in adult Kcnq1 (p = 0.04) and Dnmt1 (p = 0.02) expression in the right cortex, as well as increased expression of Tet2 in the midbrain (p = 0.03). Expression of Tet2 and Kcnq1 were positively correlated in the midbrain. Analysis of 5mC and 5hmC at the Kcnq1 locus was conducted in parallel samples using standard and oxidative bisulfite conversion followed by pyrosequencing. This analysis revealed enrichment of both 5mC and 5hmC at this locus in both brain regions. No significant changes in 5mC and 5hmC at Kcnq1 were observed with perinatal BPA exposure. Together, these data suggest that perinatal BPA exposure results in altered expression of Kcnq1, Dnmt1, and Tet2 in the adult mouse brain. Further studies with larger sample sizes are necessary to understand the mechanistic basis for these changes, as well as to determine the implications they have for brain development and function.

Dataset Information

Gene expression in the fetal mouse ovary is altered by exposure to low doses of bisphenol A.

Publications

Gene expression in the fetal mouse ovary is altered by exposure to low doses of bisphenol A.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets