Prenatal and concurrent exposure to halogenated organic compounds and gene expression of CYP17A1, CYP19A1, and oestrogen receptor α and β genes

• Published in: Occupational and environmental medicine (London, England) England), 2011-06, Vol.68 (6), p.430-437
• Main Authors: Karmaus, Wilfried, Osuch, Janet Rose, Landgraf, Jeff, Taffe, Bonita, Mikucki, Dorota, Haan, Pam
• Format: Article
• Language: English
• Subjects: 17-α-hydroxylase; Adult; Adults; Animals; aromatase; Aromatase - biosynthesis; Aromatase - genetics; Biological and medical sciences; Carrier Proteins - biosynthesis; Carrier Proteins - genetics; Chemical and industrial products toxicology. Toxic occupational diseases; Chemical hazards; Cohort Studies; Congeners; dde; Dichlorodiphenyl Dichloroethylene - blood; Dichlorodiphenyl Dichloroethylene - pharmacology; endocrine disorders; Environment; Environmental Exposure - analysis; epidemiology; Estrogen Receptor alpha - biosynthesis; Estrogen Receptor alpha - genetics; Estrogens; Female; female reproductive effects and adverse pregnancy outcomes; Fishes; Food Contamination; Gene expression; Gene Expression Regulation - drug effects; Genes; Halogenated diphenyl ethers; Humans; Hydrocarbons, Halogenated - pharmacology; Lipids; Medical sciences; Middle Aged; Nuclear Proteins - biosynthesis; Nuclear Proteins - genetics; oestrogen receptor; PBDE; PCB; pesticides; Polychlorinated biphenyls; Polychlorinated Biphenyls - blood; Polychlorinated Biphenyls - pharmacology; Pregnancy; prenatal exposure; Prenatal Exposure Delayed Effects; Receptors; Steroid 17-alpha-Hydroxylase - biosynthesis; Steroid 17-alpha-Hydroxylase - genetics; Toxicology; Various organic compounds; women; Young Adult
• ISSN: 1351-0711; 1470-7926
• DOI: 10.1136/oem.2009.053249

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.