Reproductive phenotypes in mice with targeted disruption of the 20α-hydroxysteroid dehydrogenase gene
Reproductive phenotypes in mice with targeted disruption of the 20α-hydroxysteroid dehydrogenase gene
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DOI：
10.1262/jrd.18125
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发表时间：
2007-06-01
影响因子：
1.8
通讯作者：
Nishihara, Masugi
中科院分区：
文献类型：
--
作者：
Ishida, Maho;Choi, Jae-hyek;Nishihara, Masugi
在大鼠和小鼠的黄体中，20 α -羟基类固醇脱氢酶（20 α - hsd）催化黄体酮转化为无生物活性的代谢物20 α -二氢黄体酮（20 α - ohp）。孕酮减少20 α - hsd被认为对这些啮齿类动物的功能性黄体溶解很重要。除了黄体外，20 α - hsd在胎盘、子宫内膜上皮和胎儿皮肤等组织中也有表达，尽管它在后者的组织中所起的作用仍有待确定。为了更广泛地确定20 α - hsd对功能性黄体溶解和啮齿动物生殖系统的贡献，我们产生了一种靶向破坏20 α - hsd基因的小鼠品系。在我们获得的20只α - hsd -/-小鼠中，缺乏催化反应必需的基因组区域，在假妊娠或妊娠期间，黄体中没有检测到20 α - hsd活性，也没有检测到血清中20 α - ohp浓度的增加。20只α - hsd -/-小鼠的发情周期、假妊娠和妊娠的持续时间均显著延长，但血清孕酮水平在妊娠期下降到足以分娩幼崽的水平。此外，20只α - hsd -/-小鼠的幼崽数量，特别是活仔数量明显减少。这些发现表明，20 α - hsd在功能性黄体溶解中的作用相对较小，但它与新生小鼠的存活有关。
In the corpus luteum of rats and mice, 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) catalyzes the conversion of progesterone to a biologically inactive metabolite, 20 alpha-dihydroprogesterone (20 alpha-OHP). The reduction of progesterone by 20 alpha-HSD is believed to be important for functional luteolysis in these rodent species. In addition to the corpus luteum, expression of 20 alpha-HSD has been demonstrated in tissues such as the placenta, endometrial epithelia, and fetal skin, although the roles it plays in the latter tissues remain to be determined. To determine the contribution of 20 alpha-HSD to functional luteolysis and to the rodent reproductive system more generally, we generated a strain of mice with targeted disruption of the 20 alpha-HSD gene. In the 20 alpha-HSD-/- mice we obtained, which lacked the genomic region essential for catalytic reaction, neither 20 alpha-HSD activity in the corpus luteum nor an increase in the serum concentrations of 20 alpha-OHP during pseudopregnancy or pregnancy was detected. The durations of the estrous cycle, pseudopregnancy, and pregnancy were significantly prolonged in the 20 alpha-HSD-/- mice, although the serum progesterone levels decreased to levels low enough for delivery of pups at term of pregnancy. In addition, the number of pups, especially live pups, was markedly decreased in the 20 alpha-HSD-/- mice. These findings suggest that the role of 20 alpha-HSD in functional luteolysis is relatively minor but that it is involved in the survival of newborn mice.