uterine dysfunction in biglycan and decorin deficient mice leads to dystocia during parturition子宫功能障碍在实验和decorin缺陷小鼠在分娩导致难产.pdfVIP

Uterine Dysfunction in Biglycan and Decorin Deficient Mice Leads to Dystocia during Parturition 1 1 1 2 3 Zhiping Wu , Abraham W. Aron , Elyse E. Macksoud , Renato V. Iozzo , Chi-Ming Hai , Beatrice E. Lechner1* 1 Department of Pediatrics, Women and Infants’ Hospital of Rhode Island, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, United States of America, 2 Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America, 3 Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, Rhode Island, United States of America Abstract Cesarean birth rates are rising. Uterine dysfunction, the exact mechanism of which is unknown, is a common indication for Cesarean delivery. Biglycan and decorin are two small leucine-rich proteoglycans expressed in the extracellular matrix of reproductive tissues and muscle. Mice deficient in biglycan display a mild muscular dystrophy, and, along with mice deficient in decorin, are models of Ehlers-Danlos Syndrome, a connective tissue anomaly associated with uterine rupture. As a variant of Ehlers-Danlos Syndrome is caused by a genetic mutation resulting in abnormal biglycan and decorin secretion, we hypothesized that biglycan and decorin play a role in uterine function. Thus, we assessed wild-type, biglycan, decorin and double knockout pregnancies for timing of birth and uterine function. Uteri were harvested at embryonic days 12, 15 and 18. Nonpregnant uterine samples of the same genotypes were assessed for tissue failure rate and spontaneous and oxytocin-induced contractility. We discovered that biglycan/decorin mixed double-knockout dams displayed dystocia, were at increased risk