Reproductive phenotypes in mice with targeted disruption of the 20α-hydroxysteroid dehydrogenase gene

Abstract

In the corpus luteum of rats and mice, 20α-hydroxysteroid dehydrogenase (20α-HSD) catalyzes the conversion of progesterone to a biologically inactive metabolite, 20α-dihydroprogesterone (20α-OHP). The reduction of progesterone by 20α-HSD is believed to be important for functional luteolysis in these rodent species. In addition to the corpus luteum, expression of 20α-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 20α-HSD to functional luteolysis and to the rodent reproductive system more generally, we generated a strain of mice with targeted disruption of the 20α-HSD gene. In the 20α-HSD-/- mice we obtained, which lacked the genomic region essential for catalytic reaction, neither 20α-HSD activity in the corpus luteum nor an increase in the serum concentrations of 20α-OHP during pseudopregnancy or pregnancy was detected. The durations of the estrous cycle, pseudopregnancy, and pregnancy were significantly prolonged in the 20α-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 20α-HSD-/- mice. These findings suggest that the role of 20α-HSD in functional luteolysis is relatively minor but that it is involved in the survival of newborn mice.