Loss of the Peroxisome Proliferation-activated Receptor gamma (PPARγ) Does Not Affect Mammary Development and Propensity for Tumor Formation but Leads to Reduced Fertility

The peroxisome proliferation-activated receptor gamma (PPARγ) is expressed in many cell types including mammary epithelium, ovary, macrophages, and B- and T-cells. PPARγ has an anti-proliferative effect in pre-adipocytes and mammary epithelial cells, and treatment with its ligands reduced the progression of carcinogen-induced mammary tumors in mice. Because PPARγ-null mice die in utero it has not been possible to study its role in development and tumorigenesis in vivo. To investigate whether PPARγ is required for the establishment and physiology of different cell types, a cell-specific deletion of the gene was carried out in mice using the Cre-loxP recombination system. We deleted the PPARγ gene in mammary epithelium using WAP-Cre transgenic mice and in epithelial cells, B- and T-cells, and ovary cells using MMTV-Cre mice. The presence of PPARγ was not required for functional development of the mammary gland during pregnancy and for the establishment of B- and T-cells. In addition, no increase in mammary tumors was observed. However, loss of the PPARγ gene in oocytes and granulosa cells resulted in impaired fertility. These mice have normal populations of follicles, they ovulate and develop corpora lutea. Although progesterone levels are decreased and implantation rates are reduced, the exact cause of the impaired fertility remains to be determined.

This research was originally published in the Journal of Biological Chemistry. Yongzhi Cui, Keiko Miyoshi, Estefania Claudio, Ulrich K. Siebenlist, Frank J. Gonzalez, Jodi Flaws, Kay-Uwe Wagner and Lothar Hennighausen. Loss of the Peroxisome Proliferation-activated Receptor gamma (PPARγ) Does Not Affect Mammary Development and Propensity for Tumor Formation but Leads to Reduced Fertility. J. Biol. Chem. 2002; 277(20):17830-17835.

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