Perfluorooctanoic acid effects on steroid hormone and growth factor levels mediate stimulation of peripubertal mammary gland development in C57Bl/6 mice

Yong Zhao, Ying S. Tan, Sandra Z. Haslam, Chengfeng Yang

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


Perfluorooctanoic acid (PFOA) is a synthetic, widely used perfluorinated carboxylic acid and a persistent environmental pollutant. It is an agonist of peroxisome proliferator-activated receptor α (PPARα). Studies have shown that PFOA causes hepatocellular hypertrophy, tumorigenesis, and developmental toxicity in rodents, and some of its toxicity depends on the expression of PPARα. Our recent study revealed a stimulatory effect of peripubertal PFOA treatment (5 mg/kg) on mammary gland development in C57Bl/6 mice. The present study was designed to examine the underlying mechanism(s). It was found that mammary gland stimulation by PFOA was similarly observed in PPARα knockout and wild-type C57Bl/6 mice. The presence of ovaries was required for PFOA treatment (5 mg/kg) to stimulate mammary gland development with significant increases in the levels of enzymes involved in steroid hormone synthesis in both PFOA-treated wild-type and PPARα knockout mouse ovaries. PFOA treatment significantly increased serum progesterone (P) levels in ovary-intact mice and also enhanced mouse mammary gland responses to exogenous estradiol (E), P, and E + P. In addition, PFOA treatment resulted in elevated mammary gland levels of epidermal growth factor receptor (EGFR), estrogen receptor α, amphiregulin (Areg, a ligand of EGFR), hepatocyte growth factor, cyclin D1, and proliferating cell nuclear antigen (PCNA) in both wild-type and PPARα knockout mouse mammary glands. These results indicate that PFOA stimulates mammary gland development in C57Bl/6 mice by promoting steroid hormone production in ovaries and increasing the levels of a number of growth factors in mammary glands, which is independent of the expression of PPARα.

Original languageEnglish
Pages (from-to)214-224
Number of pages11
JournalToxicological Sciences
Issue number1
StatePublished - May 2010

Bibliographical note

Funding Information:
Breast Cancer and the Environment Research Centers grant (U01 ES/CA 012800) from the National Institute of Environmental Health Science and the National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services.


  • Growth factors
  • Mammary gland development
  • Perfluorooctanoic acid
  • Peroxisome proliferator-activated receptor α
  • Progesterone
  • Puberty

ASJC Scopus subject areas

  • Toxicology


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