Involvement of 20α-Hydroxysteroid Dehydrogenase in the Maintenance of Pregnancy in Mice
Involvement of 20α-Hydroxysteroid Dehydrogenase in the Maintenance of Pregnancy in Mice
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DOI：
10.1262/jrd.20045
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发表时间：
2008-12-01
影响因子：
1.8
通讯作者：
Nishihara, Masugi
中科院分区：
文献类型：
--
作者：
Chop, Jae-hyek;Ishida, Maho;Nishihara, Masugi
酶20 α-羟基类固醇脱氢酶（20 α-HSD）将孕酮分解代谢成生物学上无活性的类固醇，20 α-二氢孕酮（20 α-OHP）。在大鼠和小鼠的黄体中，20 α-HSID被认为参与功能性黄体溶解。它也分布在其他组织中，包括胎盘、子宫内膜上皮和胎儿皮肤，尽管它在这些组织中的作用仍有待阐明。在本研究中，我们研究了20 α-HSD在维持妊娠中的作用，使用20 α-HSD基因靶向破坏的小鼠。我们首先证实，20对α-HSD-/-中的幼仔数量显著小于20对α-HSD +/+中的幼仔数量。然后，我们使20只α-HSD +/-雄性和雌性交配，使得每只怀孕雌性产生20只α-HSD +/+、20只α-HSD +/-和20只α-HSD-/-后代。子代的基因型比例不符合孟德尔遗传规律，20个α-HSD +/-和20个α-HSD-/-子代的数量小于预期值。妊娠第13、15、18天胎儿的基因型比例符合孟德尔定律，但妊娠第18天胎儿总数明显少于妊娠第13天，提示妊娠晚期胎儿丢失。接下来，我们将20个α-HSD +/+胚胎转移到20个α-HSD +/+或20个α-HSD-/-雌性中，发现20个α-HSD-/-母鼠的后代数量显著少于20个α-HSD +/+母鼠。20 α-HSD mRNA在胎儿、胎盘和子宫中的表达从妊娠第11天到第18天逐渐增加。此外，20只alpha-HSD-/-胎儿中的孕酮浓度显着高于20只alpha-HSD +/+胎儿，而20只alpha-HSD-/-胎儿中的20只alpha-OHP浓度低于20只alpha-HSD +/+胎儿。这些结果表明，母体和胎儿20 α-HSD至少部分通过降低胎儿中的孕酮浓度在维持正常妊娠中发挥作用。
The enzyme 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) catabolizes progesterone into a biologically inactive steroid, 20 alpha-dihydroprogesterone (20 alpha-OHP). In the corpora lutea of rats and mice, 20 alpha-HSID is considered to be involved in functional luteolysis. It is also distributed in other tissues including the placenta, endometrial epithelia and fetal skin, although the roles it plays in these tissues remain to be elucidated. In the present Study, we investigated the role of 20 alpha-HSD in the maintenance of pregnancy using mice with targeted disruption of the 20 alpha-HSD gene. We first confirmed that the number of pups was significantly smaller in 20 alpha-HSD-/- pairs than in 20 alpha-HSD+/+ pairs. We then mated 20 alpha-HSD+/- males and females so that each pregnant female produced 20 alpha-HSD+/+, 20 alpha-HSD+/- and 20 alpha-HSD-/- offspring. The genotype ratio of the offspring did not match the Mendel's law of inheritance, and the numbers of 20 alpha-HSD+/- and 20 alpha-HSD-/- offspring were smaller than expected values. Although the genotype ratio of fetuses on days 13, 15 and 18 of pregnancy matched the Mendel's law, the total number of fetuses on day 18 was significantly smaller than that oil day 13, suggesting that fetal loss occurred during late pregnancy. Next, we transferred 20 alpha-HSD+/+ embryos to 20 alpha-HSD+/+ or 20 alpha-HSD-/- females and found that the number of offspring was significantly smaller in 20 alpha-HSD-/- dams than in 20 alpha-HSD+/+ dams. Expression of 20 alpha-HSD mRNA in the fetus, placenta and uterus progressively increased from day 11 to 18 of pregnancy. In addition, concentrations of progesterone were significantly higher in the 20 alpha-HSD-/- fetuses than in the 20 alpha-HSD+/+ fetuses, while those of 20 alpha-OHP were lower in the 20 alpha-HSD-/- fetuses than in the 20 alpha-HSD+/+ fetuses. These results suggest that both maternal and fetal 20 alpha-HSD play a role in maintaining normal pregnancy at least partially by reducing progesterone concentrations in fetuses.