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

Departments of Molecular Genetics (M.S.M., D.W.R.) and Obstetrics and Gynecology (A.P., R.A.W.) University of Texas Southwestern Medical Center Dallas, Texas 75235

Successful delivery of the fetus (parturition) depends on coordinate interactions between the uterus and cervix. A majority (70%) of mice deficient in the type 1 isozyme of steroid 5-reductase fail to deliver their young at term and thus manifest a parturition defect. Using in vitro and in vivo measurements we show here that rhythmic contractions 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 endocrinological assays. Impaired metabolism of progesterone in the cervix of the mutant mice in late gestation leads to an accumulation of this steroid in the tissue. We conclude that a failure of cervical ripening underlies the parturition defect in mice lacking steroid 5-reductase type 1 and that this enzyme normally plays an essential role in cervical pro-gesterone catabolism at the end of pregnancy.

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