The parturition defect in steroid 5 alpha-reductase type 1 knockout mice is due to impaired cervical ripening

Successful delivery of the fetus (parturition) depends on coordinate intera ctions between the uterus and cervix. A majority (70%) of mice deficient in the type 1 isozyme of steroid 5 alpha-reductase fail to deliver their youn g at term and thus manifest a parturition defect. Using in vitro and in viv o measurements we show here that rhythmic contractions of the uterus occur normally in these mutant mice at the end of gestation. In contrast, the cer vix of the mutant animal fails to ripen at term as judged by biomechanical, histological, and endocrinological assays. Impaired metabolism of progeste rone in the cervix of the mutant mice in late gestation leads to an accumul ation of this steroid in the tissue. We conclude that a failure of cervical ripening underlies the parturition defect in mice lacking steroid tia-redu ctase type 1 and that this enzyme normally plays an essential role in cervi cal progesterone catabolism at the end of pregnancy.