Exposure to Omentum Adipose Tissue Conditioned Medium from Obese Pregnant Women Promotes Myometrial Artery Dysfunction

Aim: Underlying mechanisms of poor pregnancy outcome in obese mothers (body mass index; BMI ≥30kg/m2) are unknown. Our studies demonstrate that obese pregnant women have altered myometrial artery (MA) function related to the thromboxane and nitric oxide pathways. In obesity, increased central fat mass is associated with an altered endocrine milieu. We tested the hypothesis that in obese pregnant women the omentum, a central fat store, releases factors which promote normal MAs to dysfunction.
Methods: Myometrial and omental adipose tissue biopsies were obtained from women with uncomplicated term pregnancies. Omental adipose tissue explants from 6 normal weight (NW; BMI 18.5-24.9kg/m2) and 6 obese (OB; BMI ≥30kg/m2) women were cultured and the conditioned medium collected and pooled to produce NW medium and OB medium. Adipokine concentrations were measured using ELISAs. Wire myography was used to assess the effect of conditioned medium (NW or OB; N=7) or leptin (100nM; N=5) exposure on MA responses to U46619 (thromboxane-mimetic) and bradykinin (BK; endothelial-dependent vasodilator).
Results: OB medium had higher leptin and lower adiponectin levels than NW medium. U46619 and BK concentration-response curves were shifted upwards in MAs exposed to OB medium but were unaffected by leptin.
Conclusions: Omental adipose tissue from OB pregnant women produced altered concentrations of adipokines. Acute OB medium exposure induced MA dysfunction, an effect not mirrored by exposure to leptin. These data suggest an aberrant endocrine environment created by increased central adiposity in OB pregnant women induces vascular endothelial dysregulation, which may predispose them to poor pregnancy outcome.