Vascular endothelial growth factor is bound in amniotic fluid and maternal serum

1. The objectives of the study were: (i) to investigate the serum concentrations of vascular endothelial growth factor (VEGF) in pregnant and non-pregnant women; and (ii) to study the relationship between the levels of maternal serum VEGF and the serum concentrations of human chorionic gonadotrophin (hCG) and progesterone during the first trimester. 2. Total immunoreactive VEGF was measured by competitive RIA using recombinant human VEGF165 and a polyclonal antiserum. Serum VEGF was measured in 60 non-pregnant women of child-bearing age. These data were compared with serum VEGF measured in 363 women between 41 and 91 days of gestation. 3. The median serum VEGF concentration was 1.10 μg/l (interquartile range 0.91–1.30) in the nonpregnant women and 2.13 μg/l (interquartile range 1.62–2.77) in the pregnant women. Serum levels of VEGF were significantly higher among the pregnant cohort (P < 0.0001). Serum VEGF concentration was positively correlated with gestational age, increasing until ten completed weeks of pregnancy. Serum VEGF was negatively correlated with maternal height and weight, and positively correlated with serum hCG and serum progesterone (P ≤ 0.0001 in all cases). Serum VEGF was lower in the pregnant women who smoked (P = 0.06). 4. Our data show a positive and highly significant correlation between maternal serum levels of VEGF and hormones reflecting placental function (hCG, progesterone). We speculate that VEGF production is increased by progesterone and hCG, and that VEGF has a positive influence on trophoblast development. VEGF may also be involved in the initiation of the maternal cardiovascular adaptation to pregnancy.

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00070.2014 ◽

2014 ◽

Vol 307 (3) ◽

pp. R354-R360 ◽

Cited By ~ 6

Author(s):

Cecilia Y. Cheung ◽

Michael K. Beardall ◽

Debra F. Anderson ◽

Robert A. Brace

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Amniotic Fluid ◽

Absorption Rate ◽

Mrna Levels ◽

Vascular Endothelial ◽

Fetal Sheep ◽

Fluid Infusion ◽

Caveolin 1 ◽

Endothelial Growth Factor

We hypothesized that prostaglandin E2 (PGE2) stimulates amniotic fluid transport across the amnion by upregulating vascular endothelial growth factor (VEGF) expression in amnion cells and that amniotic PGE2 concentration correlates positively with intramembranous (IM) absorption rate in fetal sheep. The effects of PGE2 at a range of concentrations on VEGF164 and caveolin-1 gene expressions were analyzed in cultured ovine amnion cells. IM absorption rate, amniotic fluid (AF) volume, and PGE2 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, PGE2 induced dose- and time-dependent increases in VEGF164 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 PGE2. In sheep fetuses, urine replacement reduced amniotic PGE2 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 PGE2 concentration was unchanged. Neither IM absorption rate nor AF volume correlated with amniotic PGE2 concentration under each experimental condition. Although PGE2 at micromolar concentrations induced dose-dependent responses in VEGF and caveolin-1 gene expression in cultured amnion cells consistent with a role of PGE2 in activating VEGF to mediate AF transport across the amnion, amniotic PGE2 at physiological nanomolar concentrations does not appear to regulate IM absorption rate or AF volume.

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