The Parturition Defect in Steroid 5 -Reductase Type 1 Knockout Mice Is Due to Impaired Cervical Ripening

Abstract

Successful delivery of the fetus (parturition) de- pends on coordinate interactions between the uterus and cervix. A majority (70%) of mice defi- cient in the type 1 isozyme of steroid 5a-reductase fail to deliver their young at term and thus manifest a parturition defect. Using in vitro and in vivo mea- surements we show here that rhythmic contrac- tions of the uterus occur normally in these mutant mice at the end of gestation. In contrast, the cervix of the mutant animal fails to ripen at term as judged by biomechanical, histological, and endocrinolog- ical assays. Impaired metabolism of progesterone in the cervix of the mutant mice in late gestation leads to an accumulation of this steroid in the tis- sue. We conclude that a failure of cervical ripening underlies the parturition defect in mice lacking steroid 5a-reductase type 1 and that this enzyme normally plays an essential role in cervical pro- gesterone catabolism at the end of pregnancy. (Molecular Endocrinology 13: 981-992, 1999)