Padol Amol R, Sukumaran Susanth V, Sadam Abdul, Kesavan Manickam, Arunvikram Kandasamy, Verma Ankita D, Srivastava Vivek, Panigrahi Manjit, Singh Thakur Uttam, Telang Avinash G, Mishra Santosh K, Parida Subhashree
Division of Pharmacology and ToxicologyICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India.
Division of Animal Genetics and BreedingICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India.
Reproduction. 2017 May;153(5):565-576. doi: 10.1530/REP-16-0446.
High cholesterol is known to negatively affect uterine contractility in conditions. The aim of the present study was to reveal the effect of 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 CaCl 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, 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.
众所周知，高胆固醇会对某些情况下的子宫收缩产生负面影响。本研究的目的是揭示高胆固醇血症对妊娠晚期小鼠子宫自发收缩和催产素诱导的子宫收缩的影响。给雌性瑞士白化小鼠喂食高胆固醇（HC）饮食（0.5%胆酸钠、1.25%胆固醇和15%脂肪）6周，然后在交配后的整个妊娠期继续喂食。在妊娠第19天，与喂食标准饮食的对照动物相比，喂食HC饮食的动物血清胆固醇水平增加了3倍以上，而甘油三酯水平降低。在张力实验中，自发收缩的平均积分张力以及高钾去极化组织中对氯化钙的反应均未改变，但与对照相比，高胆固醇血症小鼠子宫条中催产素诱导的浓度依赖性收缩反应减弱。同样，高胆固醇血症减弱了由GNAQ蛋白激活剂毒素引发的浓度依赖性子宫收缩。然而，它对血浆或子宫组织中的内源性催产素水平没有影响。它也不影响催产素刺激组织中的前列腺素释放。蛋白质印迹数据显示，高胆固醇血症小鼠子宫中小窝蛋白-1和GRK6蛋白显著增加，但催产素受体、GNAQ和RHOA蛋白表达下降。本研究结果表明，高胆固醇血症可能通过导致催产素受体下调并抑制通过GNAQ和RHOA蛋白的信号传导效率，从而减弱妊娠晚期催产素的子宫收缩作用。
