Hypercholesterolemia impairs oxytocin-induced uterine contractility in late pregnant mouse.

Reproduction (Cambridge, England) 2017 May

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High cholesterol is known to negatively affect uterine contractility in ex vivo conditions. The aim of the present study was to reveal the effect of in vivo hypercholesterolemia on spontaneous and oxytocin-induced uterine contractility in late pregnant mouse uterus. Female Swiss albino mice were fed with high cholesterol (HC) diet (0.5% sodium cholate, 1.25% cholesterol and 15% fat) for 6 weeks and then throughout the gestation period after mating. On day 19 of gestation, serum cholesterol level was increased more than 3-fold while triglycerides level was reduced in HC diet-fed animals as compared to control animals fed with a standard diet. In tension experiments, neither the mean integral tension of spontaneous contractility nor the response to CaCl2 in high K+-depolarized tissues was altered, but the oxytocin-induced concentration-dependent contractile response in uterine strips was attenuated in hypercholesterolemic mice as compared to control. Similarly, hypercholesterolemia dampened concentration-dependent uterine contractions elicited by a GNAQ protein activator, Pasteurella multocida toxin. However, it had no effect on endogenous oxytocin level either in plasma or in uterine tissue. It also did not affect the prostaglandin release in oxytocin-stimulated tissues. Western blot data showed a significant increase in caveolin-1 and GRK6 proteins but decline in oxytocin receptor, GNAQ and RHOA protein expressions in hypercholesterolemic mouse uterus. The results of the present study suggest that hypercholesterolemia may attenuate the uterotonic action of oxytocin in late pregnancy by causing downregulation of oxytocin receptors and suppressing the signaling efficacy through GNAQ and RHOA proteins. © 2017 Society for Reproduction and Fertility.

Citation

Amol R Padol, Susanth V Sukumaran, Abdul Sadam, Manickam Kesavan, Kandasamy Arunvikram, Ankita D Verma, Vivek Srivastava, Manjit Panigrahi, Thakur Uttam Singh, Avinash G Telang, Santosh K Mishra, Subhashree Parida. Hypercholesterolemia impairs oxytocin-induced uterine contractility in late pregnant mouse. Reproduction (Cambridge, England). 2017 May;153(5):565-576