Perinatal exposure to low-dose DE-71 increases serum thyroid hormones and gonadal osteopontin gene expression

Abstract

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.

Parental Transfer of Polybrominated Diphenyl Ethers (PBDEs) and Thyroid Endocrine Disruption in Zebrafish

“…38 A significant growth inhibition was also observed in F1 larvae in our study, which was consistent with the results of previous report indicating that PBDEs disruption of TH production in rat F1 offspring causes growth impairment. 39 In our study, significant levels of DE-71 were detected in the eggs, indicating that DE-71 was transferred from exposed adult fish to their offspring. Furthermore, these PBDEs can also directly disrupt thyroid function and development in the larvae.…”

Bioconcentration and metabolism of decabromodiphenyl ether (BDE-209) result in thyroid endocrine disruption in zebrafish larvae

“…However, elevated T3 concentrations were measured in mice upon DE-71 treatment (Blake et al, 2011). Other studies have indicated that the effects of PBDEs on T3 levels were much smaller than those on T4 levels in mammals and fish (Zhou et al, 2001;Tomy et al, 2004).…”

Impact of co-exposure with lead and decabromodiphenyl ether (BDE-209) on thyroid function in zebrafish larvae

“…(Hakk et al, 2002) or in rat offspring after perinatal exposure to the penta-mixture DE-71 (Blake et al, 2011). Long-term (150 days) exposure to DE-71 by zebrafish also leads to higher plasma concentrations of T 4 (Yu et al, 2011).…”