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

Yong Zhao, Ying S. Tan, Mark J. Strynar, Gloria Perez, Sandra Z. Haslam, Chengfeng Yang

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


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.

Original languageEnglish
Pages (from-to)563-576
Number of pages14
JournalReproductive Toxicology
Issue number4
StatePublished - Jul 2012

Bibliographical note

Funding Information:
This work was supported by the Breast Cancer and the Environment Research Centers Grant U01 ES/CA 012800 from the National Institute of Environment Health Science (NIEHS) and the National Cancer Institute (NCI), National Institutes of Health (NIH), Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS or NCI, NIH. The authors would like to thank Jeffery Leipprandt, Jessica Bennett, Lisa Ann Zustiak and Dr. Jianwei Xie for their excellent technical assistance in animal model studies.


  • Growth factors
  • Mammary gland development
  • Perfluorooctanoic acid (PFOA)
  • Peroxisome proliferator-activated receptor α (PPARα)
  • Puberty
  • Steroid hormones

ASJC Scopus subject areas

  • Toxicology


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