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Progesterone and Prostaglandin H Synthase‐2 Involvement in Alcohol‐Induced Preterm Birth in Mice
Author(s) -
Cook Jocelynn L.,
Zaragoza Dean B.,
White Nancy M.,
Randall Carrie L.,
Olson David M.
Publication year - 1999
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1999.tb04075.x
Subject(s) - atp synthase , prostaglandin , alcohol , medicine , chemistry , endocrinology , obstetrics , andrology , enzyme , biochemistry
Background : Recently, an association between alcohol consumption during pregnancy and shortened gestational length has been reported, but the underlying mechanisms remain unknown. Progesterone (P 4 ) and prostaglandins have been shown to play important roles in parturition in both human and animal models. Recently, it has been suggested that prostaglandin H synthase‐2 (PGHS‐2) is responsible for prostaglandin changes associated with term and preterm 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 1 : Pregnant dams treated with either vehicle or alcohol (6 g/kg, intragastrically) on gestational day (GD) 16 were killed at various times in gestation up to the time of delivery. Plasma P 4 levels were measured 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 C57BW6J females were treated with either P 4 (2.0 mg, subcutaneously) or vehicle (sesame oil) 2 hr before receiving either 6 g/kg alcohol (intragastrically) or vehicle (isocaloric sucrose) on gestational day (GD) 16. Results indicate that P, pretreatment effectively antagonized alcohol‐induced preterm delivery. Experiment 3 : On GD16, pregnant dams received either 100 mgkg nimesulide (a specific PGHS‐2 inhibitor) or vehiclc (saline) subcutaneously, 2 hr before treatment with either 6 g/kg alcohol (given intragastrically) or isocaloric sucrose. Nimesulide was effective in antagonizing alcohol‐induced preterm labor. Conclusions : Together, these data suggest that both P 4 and PGHS‐2 may play roles in alcohol‐induced preterm birth.