Progesterone and prostaglandin H synthase-2 involvement in alcohol-inducedpreterm birth in mice

Background: Recently, an association between alcohol consumption during pre gnancy and shortened gestational length has been reported, but the underlyi ng mechanisms remain unknown. Progesterone (P-4) and prostaglandins have be en shown to play important roles in parturition in both human and animal mo dels. Recently, it has been suggested that prostaglandin H synthase-2 (PGHS -2) is responsible for prostaglandin changes associated with term and prete rm labor. It is possible that alcohol induces preterm birth by altering P-4 or PGHS-2 levels. These studies were designed to determine the role of P-4 and PGHS-2 in alcohol-induced preterm labor in mice. Methods: Experiment I: Pregnant dams treated with either vehicle or alcohol (6 g/kg, intragastrically) on gestational day (GD) 16 were killed at vario us times in gestation up to the time of delivery. Plasma P-4 levels were me asured by radioimmunoassay and uterine PGHS-2 mRNA expression was measured by Ribonuclease Protection Assay. Results indicated that alcohol treatment was associated with an earlier decline in plasma P-4 levels and an earlier rise in uterine PGHS-2 mRNA levels during gestation. Experiment 2: Pregnant C57BL/6J females were treated with either P-4 (2.0 mg, subcutaneously) or vehicle (sesame oil) 2 hr before receiving either 6 g/kg alcohol (intragast rically) or vehicle (isocaloric sucrose) on gestational day (GD) 16. Result s indicate that P-4 pretreatment effectively antagonized alcohol-induced pr eterm delivery. Experiment 3: On GD16, pregnant dams received either 100 mg /kg nimesulide (a specific PGHS-2 inhibitor) or vehicle (saline) subcutaneo usly, 2 hr before treatment with either 6 g/kg alcohol (given intragastrica lly) or isocaloric sucrose. Nimesulide was effective in antagonizing alcoho l-induced preterm labor. Conclusions: Together, these data suggest that both P-4 and PGHS-2 may play roles in alcohol-induced preterm birth.