Uterine Dysfunction in Biglycan and Decorin Deficient Mice Leads to Dystocia during Parturition

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 of delayed labor onset, and showed increased tissue failure in a predominantly decorin-dependent manner. In vitro spontaneous uterine contractile amplitude and oxytocin-induced contractile force were decreased in all biglycan and decorin knockout genotypes compared to wild-type. Notably, we found no significant compensation between biglycan and decorin using quantitative real time PCR or immunohistochemistry. We conclude that the biglycan/decorin mixed double knockout mouse is a model of dystocia and delayed labor onset. Moreover, decorin is necessary for uterine function in a dose-dependent manner, while biglycan exhibits partial compensatory mechanisms in vivo. Thus, this model is poised for use as a model for testing novel targets for preventive or therapeutic manipulation of uterine dysfunction

Life outcomes influenced by war-related experiences during the Gulf crisis

This study examined the life outcomes of children exposed to the Gulf crisis in 1990 – 1991. We expected war-trauma exposure and psychological distress symptoms to predict poorer educational and occupational outcomes. Participants were 151 Kuwaiti citizens who were assessed during childhood (in 1993; M age = 10.6 years), and who were reassessed 10 years later in young adulthood (in 2003; M age = 21.2 years). Participants completed measures of intelligence, war-trauma exposure, posttraumatic stress symptoms, anxiety symptoms, depressive symptoms, intervening life events, and life outcomes. Results indicated that war-trauma exposure negatively impacted children’s educational and occupational outcomes as young adults. Boys with higher levels of war-trauma exposure were less likely to attend University. Posttraumatic stress and anxiety symptoms also predicted poorer educational and occupational outcomes. However, this relationship was not significant when we accounted for children’s intelligence. Depressive symptoms were not predictive of children’s educational or occupational outcomes. Results suggest that war-trauma exposure may have life altering effects on children. Tailored, early interventions are needed for children exposed to war traumas