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.