The Effects of Serum from Obese Pregnant Rats on Hypoxia‐Induced Placental sFlt‐1 Release

Abstract

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% O2). However, in face of hypoxia (1% O2), 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.