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Effects of chronic dietary exposure to low levels of PCBs (polychlorinated biphenyls) on reproduction, growth and whole body burdens were investigated in three generations of Peromyscus polionotus. Mated pairs were maintained on a diet containing 5 mg/kg PCBs (Aroclor 1254) for 12 months, beginning exposure as young adults; matched controls received a similar diet without PCBs. Offspring were maintained on the parental regime and paired at maturity with non-siblings in the same group. In first and second generation offspring, birth and weaning weights were significantly lower in PCB-exposed animals; in the second generation, there were also significantly fewer mice born/month, longer intervals prior to birth of the first litter, and decreased survival to weaning (25 days) among exposed mice. Whole body residue of PCBs increased significantly with each generation of exposure. This study clearly shows that chronic exposure to PCBs at a dosage of 5 mg/kg depressed fertility, growth and survival in Peromyscus, and that these effects were amplified through multigenerational exposure.

Polybrominated diphenyl ethers (PBDEs) are flame retardants that have been widely used in manufacturing. They are major household and environmental contaminants that bioaccumulate. Humans are exposed primarily through dust inhalation and dietary ingestion of animal products. In animal studies, high doses of penta-brominated diphenyl ethers (penta-BDEs) in the mg/kg body weight (BW) range negatively impact brain development, behavior, memory, circulating thyroid hormone concentrations, the reproductive system and bone development. We investigated the effects of ingestion of a relatively low dose of the penta-BDE mixture DE-71 by pregnant and lactating rats on reproductive and thyroid parameters of the F1 offspring. F0 mothers received 60 μg/kg BW of DE-71 or vehicle daily by gavage from Day 1.5 of pregnancy through lactation (except the day of parturition). F1 pups were sacrificed at 21 d of age or outbred at approximately 80 d of age. Bred F1 females were sacrificed at Day 14.5 of pregnancy or at five months of age. Bred F1 males were sacrificed at five months of age. DE-71 treatment of the mothers affected the F1 females as evidenced by lower body weights at 80 d and five months of age, elevated serum T3 and T4 concentrations at Day 14.5 of pregnancy and increased thyroid gland weight and ovarian osteopontin mRNA at five months of age. Perinatal DE-71 exposure also increased testicular osteopontin mRNA in 21-day-old F1 males. Utilizing a granulosa cell in vitro model, we demonstrated that DE-71 activated the rat osteopontin gene promoter. Our results are the first to demonstrate that PBDEs increase rodent circulating T3 and T4 concentrations and gonadal osteopontin mRNA, and activate the osteopontin gene promoter. These changes may have clinical implications as others have shown associations between human exposure to PBDEs and subclinical hyperthyroidism, and overexpression of ovarian osteopontin has been associated with ovarian cancer.

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