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Perfluorooctanoic acid effects on ovaries mediate its inhibition of peripubertal mammary gland development in Balb/c and C57Bl/6 mice
Citation:
Zhao, Y., Y. S. Tan, M. STRYNAR, G. Perez, S. Z. Haslam, AND C. Yang. Perfluorooctanoic acid effects on ovaries mediate its inhibition of peripubertal mammary gland development in Balb/c and C57Bl/6 mice. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, 33(4):563-576, (2012).
Impact/Purpose:
The National Exposure Research Laboratory′s (NERL′s) Human Exposure and Atmospheric Sciences Division (HEASD) conducts research in support of EPA′s mission to protect human health and the environment. HEASD′s research program supports Goal 1 (Clean Air) and Goal 4 (Healthy People) of EPA′s strategic plan. More specifically, our division conducts research to characterize the movement of pollutants from the source to contact with humans. Our multidisciplinary research program produces Methods, Measurements, and Models to identify relationships between and characterize processes that link source emissions, environmental concentrations, human exposures, and target-tissue dose. The impact of these tools is improved regulatory programs and policies for EPA.
Description:
Exposure to perfluorooctanoic acid (PFOA), a synthetic perfluorinated compound and an agonist of peroxisomes proliferator-activated receptor α (PPARα), causes stunted mouse mammary gland development in various developmental stages. However, the underlying mechanisms remain poorly understood. We found that peripubertal PFOA exposure significantly inhibited mammary gland growth in both Balb/c and C57Bl/6 wild type mice, but not in C57Bl/6 PPARα knockout mice, and Balb/c mice were more sensitive to PFOA inhibition. PFOA caused (1) delayed or absence of vaginal opening and lack of estrous cycling during the experimental period; (2) decreases in ovarian steroid hormonal synthetic enzyme levels; and (3) reduced expression of estrogen- or progesterone-induced mammary growth factors. Supplementation with exogenous estrogen and/or progesterone reversed the PFOA inhibitory effect on mammary gland. These results indicate that PFOA effects on ovaries mediate its inhibition of mammary gland development in Balb/c and C57Bl/6 mice and that PPARα expression is a contributing factor.
URLs/Downloads:
Reproductive Toxicology
Perfluorooctanoic acid effects on ovaries mediate its inhibition of peripubertal mammary gland development in Balb/c and C57Bl/6 mice (PDF, NA pp, 29 KB, about PDF)