Abstract
Maternal obesity is associated with prolonged and dysfunctional labour and emergency caesarean section, but the mechanisms are unknown. The present 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 6weeks before conception and during pregnancy. On gestational day 21 (TNL) or day 22 (TL) CON and HFHC (n=10) rats were killed to determine plasma cholesterol, triacylglycerol and progesterone concentrations and collection of myometrium for contractility studies and expression of CAPs caveolin-1 (Cav-1), connexin-43 (CX-43) and it's phosphorylated form (pCX-43), oxytocin receptor (OXTR) and cyclooxygenase-2 (COX-2). HFHC feeding increased visceral fat (P≤0.001), plasma cholesterol (P≤0.001) and triacylglycerol (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 was unaltered in CON. pCX-43 fell with labour in CON but remained high in HFHC. OXTR expression was significantly higher in HFHC compared with 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 -8.84 compared with -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.
Highlights
A previous study has identified that over 20 % of the female population in the U.K. are obese and this number is expected to double by 2050 [1]
This study focused on the contractile proteins caveolin-1 (CAV-1), connexin 43 (CX-43) and cyclooxygenase-2 (COX-2) during labour
The increased body weight in HFHC animals was associated with peri-renal and gonadal fat depots being 2-fold higher than control chow (CON) rats. (Peri-renal, CON 6.68 g +− 0.83 compared with HFHC 13.19 g +− 1.35, P 0.001; gonadal, CON 6.07 g +− 0.64 compared with HFHC 11.00 g +− 1.73, P < 0.032)
Summary
A previous study has identified that over 20 % of the female population in the U.K. are obese and this number is expected to double by 2050 [1]. CX-43 is the major myometrial gap junction protein that facilitates intracellular propagation of electrical impulses [11] and synchronizes myometrial contractions, whereas COX-2 is responsible for the synthesis of prostaglandins PGF2α (prostaglandin PGF2α) and prostaglandin PGE2 (PGE2) [12] which stimulate [13] and relax [14] myometrial contractions respectively. These findings suggest that HFHC-induced increases in adiposity could have a negative impact upon uterine contractility. This approach tested the hypothesis that a HFHC diet would negatively affect uterine contractility and uterine CAP expression within TNL and TL animals
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