Prostaglandin E2 regulation of amnion cell vascular endothelial growth factor expression: relationship with intramembranous absorption rate in fetal sheep

We hypothesized that prostaglandin E-2 (PGE(2)) stimulates amniotic fluid transport across the amnion by upregulating vascular endothelial growth factor (VEGF) expression in amnion cells and that amniotic PGE(2) concentration correlates positively with intramembranous (IM) absorption rate in fetal sheep. The effects of PGE(2) at a range of concentrations on VEGF(164) and caveolin-1 gene expressions were analyzed in cultured ovine amnion cells. IM absorption rate, amniotic fluid (AF) volume, and PGE(2) concentration in AF were determined in late-gestation fetal sheep during control conditions, isovolumic fetal urine replacement (low IM absorption rate), or intra-amniotic fluid infusion (high IM absorption rate). In ovine amnion cells, PGE(2) induced dose-and time-dependent increases in VEGF(164) mRNA levels and reduced caveolin-1 mRNA and protein levels. VEGF receptor blockade abolished the caveolin-1 response, while minimally affecting the VEGF response to PGE(2). In sheep fetuses, urine replacement reduced amniotic PGE(2) concentration by 58%, decreased IM absorption rate by half, and doubled AF volume (P < 0.01). Intra-amniotic fluid infusion increased IM absorption rate and AF volume (P < 0.01), while amniotic PGE(2) concentration was unchanged. Neither IM absorption rate nor AF volume correlated with amniotic PGE(2) concentration under each experimental condition. Although PGE(2) at micromolar concentrations induced dose-dependent responses in VEGF and caveolin-1 gene expression in cultured amnion cells consistent with a role of PGE(2) in activating VEGF to mediate AF transport across the amnion, amniotic PGE(2) at physiological nanomolar concentrations does not appear to regulate IM absorption rate or AF volume.