Maternal obesity is associated with prolonged and dysfunctional labour and emergency caesarean section, but the mechanisms are unknown. This study investigated the effects of an adiposity inducing high-fat, high-cholesterol (HFHC) diet on uterine contractile associated protein (CAP) expression and ex-vivo uterine contractility in term non-labouring (TNL) and term labouring (TL) rats. Female rats were fed either control chow (CON n=20) or HFHC (n=20) diet 6 weeks before conception and during pregnancy. On gestational day 21 (TNL) or day 22 (TL) CON and HFHC (n=10) rats were euthanized to determine plasma cholesterol, triglyceride and progesterone concentrations and collection of myometrium for contractility studies and expression of CAPs Caveolin-1 (Cav-1), connexin-43 and it’s phosphorylated form (CX-43 & pCX-43), oxytocin receptor (OXTR), and cyclooxygenase-2 (COX-2). HFHC feeding increased visceral fat ( P ≤0.001), plasma cholesterol ( P ≤0.001) and triglyceride ( P =0.039) concentrations. Stage of labour effected uterine expression of CAV-1 (P<0.02), pCX43 and COX-2 (both P<0.03). CAV-1 and pCX43 decreased but COX-2 increased with parturition. Significant diet and labour stage interactions were evident for CX-43 and pCX43 (P<0.03 and P<0.004 respectively). CX-43 decreased with TL in HFHC animals but unaltered in CON. pCX-43 fell with labour in CON but remained high in HFHC. OXTR expression was significantly higher in HFHC compared to CON animals P<0.03). Progesterone was higher in HFHC rats at term (P<0.014) but fell significantly with labour to similar concentrations as CON. Contractility studies identified synchronous contractions of stable amplitude in lean animals, but unstable asynchronous contractions with obesity. Uterine dose response to oxytocin was blunted during labour in HFHC rats with a log EC50 of -8.84M compared to -10.25M in CON for integral activity (P<0.05). In conclusion our adiposity model exhibits adverse effects on contractile activity during labour that can be investigated further to unravel the mechanisms causing uterine dystocia in obese women.
- Copyright 2015 The Author(s)
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