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The Effects of Serum from Obese Pregnant Rats on Hypoxia‐Induced Placental sFlt‐1 Release
Author(s) -
Palei Ana,
Dent Edward,
Spradley Frank,
Granger Joey
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.810.11
Subject(s) - medicine , endocrinology , preeclampsia , soluble fms like tyrosine kinase 1 , hypoxia (environmental) , placenta , placental growth factor , chemistry , vascular endothelial growth factor , biology , fetus , pregnancy , organic chemistry , oxygen , genetics , vegf receptors
Placental ischemia/hypoxia is thought to promote the release of placental anti‐angiogenic factors, such as soluble fms‐like tyrosine kinase (sFlt)‐1, into the maternal circulation that cause endothelial dysfunction and ultimately preeclampsia (PE). A leading risk factor for PE is obesity; however, the mechanisms linking obesity and PE are unknown. We have previously found that placental explants from obese rats show enhanced hypoxia‐induced sFlt‐1 release. Our present aims were to compare the effects of serum from obese and lean pregnant rats on placental sFlt‐1 secretion. Serum from obese (melanocortin‐4 receptor deficient; body weight 357±5 g and visceral fat weight 15.3±0.4 g) and lean (wild type; BW 331±11 g and VFW 9.2±0.4 g; P<0.05) pregnant rats were obtained on gestational day (GD)19. Placentas from normal pregnant Sprague Dawley rats were collected on GD19 and individual explants were cultured in plate inserts‐coated with matrigel containing medium supplemented with 5% obese or lean serum, at 37° C for 48 h. Secreted sFlt‐1 in media was measured by ELISA. There was no difference in sFlt‐1 secretion from explants incubated with obese vs. lean serum (1524±116 and 1558±69 pg/mg) under normoxia (6% O 2 ). However, in face of hypoxia (1% O 2 ), sFlt‐1 release was higher in explants incubated with obese serum compared with lean serum (1671±142 and 1462±81 pg/mg). Interestingly, while hypoxia elicited an increase in sFlt‐1 secretion from explants treated with obese serum, hypoxia did not stimulate sFlt‐1 release from explants treated with lean serum. In conclusion, our preliminary findings indicate that circulating factor(s) in obese pregnancies may promote exaggerated placental hypoxia‐induced sFlt‐1 production. Funding: 14POST18970005, HL051971 and 1T32HL105324.