Models of perinatal compromises in the guinea pig: Their use in showing the role of neurosteroids in pregnancy and the newborn

Placental progesterone production during late gestation has a major role in maintaining elevated neurosteroid levels during pregnancy. These levels of key neurosteroids, including allopregnanolone, are critical for optimal brain development during late gestation and the early neonatal period. The long gestation period (~70), in utero brain development and placental progesterone synthesis of the guineas pig makes this species very suitable for studying the mechanisms by which pregnancy compromises impact neurosteroid pathways. We have used models of intrauterine growth restriction and preterm birth to show that these challenges may suppress neurosteroid action and this likely contributes to the adverse outcomes following these conditions. Reduced allopregnanolone levels during late gestation result in reduced myelination and injurious brain cell death suggesting supplementation treatments may improve outcomes following compromised pregnancy. Guinea pig models of episodic prenatal maternal stress have been used to examine how these events lead to adverse behavioral outcomes for the offspring. We found that prenatal stress disrupts the neurosteroid pathways between the dam and fetus. Together this work indicates that compromises and stress during pregnancy and in the early neonatal period disrupt neurotropic and protective neurosteroid pathways leading to deficiencies that contribute to the adverse neurological and behavioral outcomes following these challenges. The use of neurosteroid-based supplementation therapies may represent a future range of therapeutic approaches that could be used to improve outcomes following stressful events in pregnancy and following premature birth.