Effect of Ethanol on the Release of Prostaglandins from Ovine Fetal Brain Stem during Gestation

Prostaglandins (PGs) have been implicated as mediators of the ethanol-induced suppression of ovine fetal breathing movements (FBM). The objectives of the present study were to determine the ontogeny of the in vitro efflux of PGE2 and β-keto PGF1α in ovine fetal brain stem during the second half of gestation and to determine the effect of in vitro ethanol exposure on the efflux of these PGs. Ovine fetal brain stem tissue was obtained at mean gestational ages of 80 days (n= 6), 105 days (n= 10), and 135 days (n= 16) by rapid excision following maternal euthanization. Tissue slices (400 μM thickness) were prepared from the lower pons-medulla region of the brain stem. After a 1-hr equilibration period in artificial cerebrospinal fluid, efflux of PGE2 and 6-keto PGF1α in the brain stem was determined using the brain slice-superfusion method, and the PGE2 and 6-keto PGF1α concentrations in the superfusate were determined by specific radioimmunoassay. The mean spontaneous efflux of PGE2 and 6-keto PGF1α expressed as pmol PG/gram wet weight of tissue/5-min collection period was, respectively, 31.9 ± 4.2 and 26.6 ± 2.4 at 80 days, 38.3 ± 5.2 and 29.6 ± 2.2 at 105 days, and 57.4 ± 3.1 and 27.1 ± 1.1 at 135 days of gestation. In vitro exposure to 20, 40, and 80 mM ethanol did not affect PG efflux in the brain stem at 80 and 105 days of gestation. In vitro ethanol exposure decreased PGE2 and 6-keto PGF1α efflux at 135 days of gestation to 36.8 ± 5.3% and 41.6 ± 4.3% of spontaneous efflux within 15 min, respectively; this effect of ethanol was not dose-dependent. The data do not support the hypothesis that ethanol increases PG efflux in the ovine fetal brain stem. In view of these findings and the data implicating PGs in the mechanism of ethanol-induced suppression of FBM, it is possible that ethanol acts at either central sites rostral to the brain stem (i.e., upstream CSF) or peripheral sites to increase the synthesis of PGs and their efflux into the systemic circulation, with subsequent transfer to the respiratory control region(s) of the brain stem.