Regulation of amniotic fluid volume by intramembranous absorption in sheep: role of passive permeability and vascular endothelial growth factor.
OBJECTIVE
During long-term intravascular fluid infusion in the ovine fetus, a large increase in fetal urinary flow rate occurs while amniotic fluid volume increases only slightly because of increased intramembranous absorption. The current study tested the hypotheses that passive intramembranous permeability increases in response to fetal intravascular saline solution infusion and that the increased intramembranous absorption occurs in parallel with an increase in vascular endothelial growth factor gene expression in the amnion, chorion, and placenta.


METHODS
Chronically catheterized fetal sheep that average 126 +/- 1 (SE) days of gestation either were infused intravascularly with 7 L of normal saline solution over 3 days (n = 8 sheep) or served as time controls (n = 6 sheep). Amniotic fluid volume and fetal urinary flow rate were measured daily. Intramembranous diffusional permeability was estimated daily as being equal to the clearance of intra-amniotically injected technetium 99m. Vascular endothelial growth factor messenger RNA abundance in the amnion, chorion, and placenta was determined by Northern blot analysis. Statistical analyses included analysis of variance.


RESULTS
In the infused fetuses, amniotic fluid volume and urinary flow increased (P <.01) by 891 +/- 144 mL and 3488 +/- 487 mL per day, respectively, on infusion day 3 compared with no changes over time in the control fetuses. In the infused fetuses, estimated intramembranous absorption increased by 4276 +/- 499 mL during the 3-day infusion. Intramembranous technetium 99m permeability was similar over time in the two groups. In the infused group, vascular endothelial growth factor messenger RNA levels in the amnion, chorion, and placenta increased 2- to 4-fold compared with the control group (P <.001).


CONCLUSIONS
The up-regulation of vascular endothelial growth gene expression may mediate the increase in the intramembranous absorption that is induced by volume-loading diuresis; however, this does not occur by passive mechanisms. We speculate that vascular endothelial growth mediates the increased intramembranous absorption by increasing vesicular transport.
Daneshmand
Sean S
SS
Division of Perinatal Medicine, Department of Reproductive Medicine, University of California at San Diego, La Jolla 92093, USA.
Cheung
Cecilia Y
CY
Brace
Robert A
RA
D000042:Absorption / Q000187:drug effects; D000650:Amnion / Q000378:metabolism; D000653:Amniotic Fluid / Q000378:metabolism*; D000818:Animals; D002823:Chorion / Q000378:metabolism; D004231:Diuresis / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000235:genetics / Q000502:physiology*; D005321:Extraembryonic Membranes / Q000378:metabolism*; D005260:Female; D007267:Injections; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D008222:Lymphokines / Q000235:genetics / Q000502:physiology*; D010539:Permeability; D010920:Placenta / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012756:Sheep; D012965:Sodium Chloride / Q000008:administration & dosage; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D012965:Sodium Chloride