Fetal esophageal ligation induces expression of vascular endothelial growth factor messenger ribonucleic acid in fetal membranes

OBJECTIVE: Obstruction of the fetal esophagus does not always produce the e xpected polyhydramnios. This is because of increased intramembranous absorp tion of amniotic fluid into the fetal circulation. A possible mediator for this increased absorption is vascular endothelial growth factor (VEGF). The present objective was to explore whether VEGF gene expression and action w ould be induced in fetal membranes and placentas of ovine fetuses after eso phageal ligation. STUDY DESIGN: Five late-gestation fetal sheep underwent esophageal ligation and 5 served as control animals. On postoperative day 9, amnion, chorion, and placenta were collected for cellular localization and quantitation of V EGF messenger ribonucleic acid by in situ hybridization and Northern blot a nalysis. Reverse-transcription polymerase chain reaction was used to identi fy the VEGF molecular forms. Immunostaining with Ki-67 antibody was used to determine the proliferation of vascular endothelium in the fetal membranes and placentas. RESULTS: VEGF messenger ribonucleic acid was localized in amniotic epitheli um, chorionic cytotrophoblast, and cytotrophoblast of the placenta. VEGF(16 4) was the major transcript expressed in these tissues. The abundance of VE GF messenger ribonucleic acid in the amnion and chorion, but not in the pla centa, was significantly increased in the ligated fetuses in comparison wit h the control fetuses. The proliferation of the intramembranous blood vesse l endothelium was greater in the ligated fetuses than in the control fetuse s. CONCLUSION: The levels of VEGF messenger ribonucleic acid and the prolifera tion of vascular endothelium in the amnion and chorion increased after feta l esophageal ligation. This provides a possible mechanism for the enhanced intramembranous absorption of amniotic fluid through increased vascularity and permeability of the fetal membranes, thus ameliorating the development of polyhydramnios. We speculate that the signal(s) that mediate the increas e in VEGF expression is present in either the fetal urine or the fetal lung secretions, or both.