title: Loss of the peroxisome proliferation-activated receptor gamma (PPARgamma ) does not affect mammary development and propensity for tumor formation but leads to reduced fertility.
abstract: The peroxisome proliferation-activated receptor gamma (PPARgamma) is expressed in many cell types including mammary epithelium, ovary, macrophages, and B- and T-cells. PPARgamma 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 PPARgamma-null mice die in utero it has not been possible to study its role in development and tumorigenesis in vivo. To investigate whether PPARgamma 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 PPARgamma 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 PPARgamma 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 PPARgamma 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.
authors.affiliation: Laboratory of Genetics and Physiology, NIDDK, the Laboratory of Immunoregulation, Immune Activation Section, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA. Yongzhic@intra.niddk.nih.gov
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Cui
authors.forename: Keiko
authors.initials: K
authors.lastname: Miyoshi
authors.forename: Estefania
authors.initials: E
authors.lastname: Claudio
authors.forename: Ulrich K
authors.initials: UK
authors.lastname: Siebenlist
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
authors.forename: Jodi
authors.initials: J
authors.lastname: Flaws
authors.forename: Kay-Uwe
authors.initials: KU
authors.lastname: Wagner
authors.forename: Lothar
authors.initials: L
authors.lastname: Hennighausen
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D010064:Embryo Implantation; D005260:Female; D005434:Flow Cytometry; D007247:Infertility, Female / Q000150:complications / Q000209:etiology*; D008321:Mammary Glands, Animal / Q000254:growth & development*; D015674:Mammary Neoplasms, Animal / Q000209:etiology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D011863:Radioimmunoassay; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D011374:Progesterone