Loss of the peroxisome proliferation-activated receptor gamma (PPARγ) does not affect mammary development and propensity for tumor formation but leads to reduced fertility
Loss of the peroxisome proliferation-activated receptor gamma (PPARγ) does not affect mammary development and propensity for tumor formation but leads to reduced fertility
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DOI：
10.1074/jbc.m200186200
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发表时间：
2002-05-17
影响因子：
4.8
通讯作者：
Hennighausen, L
中科院分区：
文献类型：
--
作者：
Cui, Y;Miyoshi, K;Hennighausen, L
过氧化物酶体增殖激活受体γ（PPARgamma）在许多细胞类型中表达，包括乳腺上皮、卵巢、巨噬细胞和带状T细胞。PPARgamma在前脂肪细胞和乳腺上皮细胞中具有抗增殖作用，用其配体治疗可减少致癌物诱导的小鼠乳腺肿瘤的进展。由于PPARgamma基因敲除小鼠在子宫内死亡，因此无法研究其在体内发育和肿瘤发生中的作用。为了研究不同细胞类型的建立和生理学是否需要PPARgamma，使用Cre-loxP重组系统在小鼠中进行该基因的细胞特异性缺失。我们使用WAP-Cre转基因小鼠删除乳腺上皮中的PPARgamma基因，使用MMTV-Cre小鼠删除上皮细胞、B细胞和T细胞以及卵巢细胞中的PPARgamma基因。PPARgamma的存在并不是妊娠期间乳腺功能发育和B-和T-细胞建立所必需的。此外，未观察到乳腺肿瘤增加。然而，卵母细胞和颗粒细胞中PPARgamma基因的缺失导致生育力受损。这些小鼠具有正常的卵泡群，它们排卵并发育黄体。虽然孕酮水平降低，着床率降低，但生育能力受损的确切原因仍有待确定。
The peroxisome proliferation-activated receptor gamma (PPARgamma) is expressed in many cell types including mammary epithelium, ovary, macrophages, and Band 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.