Perfluorooctanoic acid effects on ovaries mediate its inhibition of peripubertal mammary gland development in Balb/c and C57Bl/6 mice

被引：44

作者：

Zhao, Yong ^{[1
,2
]}

Tan, Ying S. ^{[1
,2
]}

Strynar, Mark J. ^{[4
]}

Perez, Gloria ^{[1
]}

Haslam, Sandra Z. ^{[1
,2
]}

Yang, Chengfeng ^{[1
,2
,3
]}

机构：

[1] Michigan State Univ, Dept Physiol, E Lansing, MI 48824 USA

[2] Michigan State Univ, Breast Canc & Environm Res Ctr, E Lansing, MI 48824 USA

[3] Michigan State Univ, Ctr Integrat Toxicol, E Lansing, MI 48824 USA

[4] US EPA, Human Exposure & Atmospher Sci Div, Natl Exposure Res Lab, Res Triangle Pk, NC 27711 USA

来源：

REPRODUCTIVE TOXICOLOGY | 2012年 / 33卷 / 04期

基金：

美国国家卫生研究院;

关键词：

Perfluorooctanoic acid (PFOA); Mammary gland development Puberty; Steroid hormones; Growth factors; Peroxisome proliferator-activated receptor alpha (PPAR alpha); ACUTE REGULATORY PROTEIN; PERFLUOROALKYL ACIDS; GROWTH-FACTOR; PROGESTERONE ACTION; ESTROGEN-RECEPTOR; BREAST-CANCER; CROSS-FOSTER; MOUSE; EXPOSURE; ALPHA;

D O I：

10.1016/j.reprotox.2012.02.004

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Exposure to perfluorooctanoic acid (PFOA), a synthetic perfluorinated compound and an agonist of peroxisome proliferator-activated receptor alpha (PPAR alpha), 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 PPAR alpha 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 PPAR alpha expression is a contributing factor. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：563 / 576

页数：14

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