title: Perfluorooctanoic acid effects on ovaries mediate its inhibition of peripubertal mammary gland development in Balb/c and C57Bl/6 mice.
abstract: Exposure to perfluorooctanoic acid (PFOA), a synthetic perfluorinated compound and an agonist of peroxisome 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.
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, MI 48824, United States; Breast Cancer and the Environment Research Center, Michigan State University, East Lansing, MI 48824, United States. Electronic address: yzhao@msu.edu.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, MI 48824, United States; Breast Cancer and the Environment Research Center, Michigan State University, East Lansing, MI 48824, United States. Electronic address: tanying@msu.edu.
authors.forename: Ying S
authors.initials: YS
authors.lastname: Tan
authors.affiliation: Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, United States. Electronic address: strynar.mark@epa.gov.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Strynar
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, MI 48824, United States. Electronic address: perezg@msu.edu.
authors.forename: Gloria
authors.initials: G
authors.lastname: Perez
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, MI 48824, United States; Breast Cancer and the Environment Research Center, Michigan State University, East Lansing, MI 48824, United States. Electronic address: shaslam@msu.edu.
authors.forename: Sandra Z
authors.initials: SZ
authors.lastname: Haslam
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, MI 48824, United States; Breast Cancer and the Environment Research Center, Michigan State University, East Lansing, MI 48824, United States; Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, United States. Electronic address: yangcf@msu.edu.
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Yang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002210:Caprylates / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005466:Fluorocarbons / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D027361:Organic Anion Transporters / Q000096:biosynthesis; D010053:Ovary / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists* / Q000235:genetics; D011374:Progesterone / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D012741:Sexual Maturation / Q000187:drug effects*; D013045:Species Specificity; D014018:Tissue Distribution
chemical_list: D002210:Caprylates; D004785:Environmental Pollutants; D004967:Estrogens; D005466:Fluorocarbons; D027361:Organic Anion Transporters; D047493:PPAR alpha; D011374:Progesterone; C023036:perfluorooctanoic acid