Progesterone and prostaglandin H synthase-2 involvement in alcohol-induced preterm birth in mice.
BACKGROUND
Recently, an association between alcohol consumption during pregnancy and shortened gestational length has been reported, but the underlying mechanisms remain unknown. Progesterone (P4) 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 P4 or PGHS-2 levels. These studies were designed to determine the role of P4 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 P4 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 P4 levels and an earlier rise in uterine PGHS-2 mRNA levels during gestation. Experiment 2: Pregnant C57BL/6J females were treated with either P4 (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 P4 pretreatment effectively antagonized alcohol-induced preterm delivery. Experiment 3: On GD16, pregnant dams received either 100 mg/kg nimesulide (a specific PGHS-2 inhibitor) or vehicle (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 P4 and PGHS-2 may play roles in alcohol-induced preterm birth.
Cook
J L
JL
Perinatal Research Centre, Department of Obstetrics, University of Alberta, Edmonton, Canada. jlc21@gpu.srv.ualberta.ca
Zaragoza
D B
DB
White
N M
NM
Randall
C L
CL
Olson
D M
DM
D000818:Animals; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism*; D007743:Labor, Obstetric / Q000097:blood* / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D007752:Obstetric Labor, Premature / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy; D011247:Pregnancy; D011374:Progesterone / Q000097:blood*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism*; D013449:Sulfonamides / Q000627:therapeutic use
D002492:Central Nervous System Depressants; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D013449:Sulfonamides; D000431:Ethanol; D011374:Progesterone; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C012655:nimesulide