Objective To determine whether prenatal exposure to dichlorodiphenyl ethylene (DDE) and polychlorinated biphenyls (PCBs) and concurrent exposure to DDE, PCBs and polybrominated diphenylethers (PBDEs) affect gene expression of aromatase (CYP19A1), 17-α-hydroxylase (CYP17A1), and oestrogen receptors α and β (ESR 1 and ESR2).
Methods Based on maternal PCB and DDE levels in the parent generation of the Michigan Fisheater Cohort determined between 1973 and 1991, individual prenatal exposures were estimated and have been published. In 2007, female adult offspring of this cohort were examined. Gene expression and concurrent lipid-adjusted exposures to DDE, PCBs and PBDEs were measured in blood and serum, respectively. Using mixed models and path analyses, gene-expression data were regressed on prenatal and concurrent exposures controlling for confounders.
Results 139 daughters of Michigan fisheaters (65.3%) participated in the investigation. While prenatal PCB levels were statistically significantly associated with decreased expression of the aromatase and 17-α-hydroxylase genes, prenatal DDE levels were significantly related to increased gene expression of aromatase but not of 17-α-hydroxylase. The DDE association seems to be mediated by concurrent lipid-adjusted p,p′-DDE serum levels. Prenatal and concurrent exposure of both PCBs and DDE had comparable effects. No association was found for PBDEs or for the gene expression of ESR 1 and ESR2.
Conclusions A 40-year antecedent prenatal exposure and concurrent levels of PCBs and DDE are associated with the expression of aromatase and 17-α-hydroxylase genes. Prenatal exposures to organochlorines may instigate long-term alterations of gene expression. Mechanisms of prenatal induction of persistent gene-expression alterations are speculated to be epigenetic in nature.
- Gene expression
- women, aromatase
- oestrogen receptor
- prenatal exposure
- endocrine disorders
- female reproductive effects and adverse pregnancy outcomes
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Funding This research was supported by three grants from the Agency for Toxic Substances and Disease Registry (H75/ATH582536, R01 TS000007 and R01 TS000069).
Competing interests None.
Patient consent Obtained.
Ethics approval Ethics approval was provided by the Michigan State University, Michigan Department of Community Health, University of South Carolina.
Provenance and peer review Not commissioned; externally peer reviewed.
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