脂联素通过上调PPARα/HOXA10通路改善多囊卵巢综合征大鼠的子宫内膜容受性
[Adiponectin improves endometrial receptivity in rats with polycystic ovary syndrome by upregulating the PPARα/HOXA10 pathway].
作者信息
Wang J, Yang W, Liu J, Shi J, Xiao P, Li M
机构信息
Microscopic Morphology Experimental Center//The Institute of Clinical Anatomy and Reproductive Medicine// Department of Histology and Embryology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
Department of Reproductive Medical Center, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410002, China.
出版信息
Nan Fang Yi Ke Da Xue Xue Bao. 2024 Feb 20;44(2):298-307. doi: 10.12122/j.issn.1673-4254.2024.02.12.
OBJECTIVE
To explore the role of the PPARα/HOXA10 signaling pathway in mediating the effect of adiponectin (APN) for improving endometrial receptivity in a rat model of polycystic ovary syndrome (PCOS).
METHODS
Forty female SD rat models with letrozole-induced PCOS were randomized, with 10 normal rats as the control, into 4 equal groups for treatment with APN alone, APN combined with GW6471 (a specific PPARα inhibitor) or the vehicle for 20 days, or no further treatment (PCOS model group). GW6471 treatment (daily dose of 1 mg/kg) and vehicle treatment were initiated on the 11th day following the start of APN treatment, all administered via intraperitoneal injection. The rats were observed for changes in estrous cycle, body weight, ovarian index and morphology, uterine index and morphology, serum hormone levels and lipid metabolism parameters. Endometrial expressions of PPARα and HOXA10 were detected with immunohistochemistry and Western blotting. The development of endometrial pinopodes was observed under electron microscope, and pregnancies of the rats were recorded.
RESULTS
The rat models of PCOS exhibited obvious estrous cycle disorders with significantly prolonged estrous interval, increased body weight and ovarian index, decreased uterine index, disordered serum hormones and lipid metabolism ( < 0.05), and polycystic ovarian changes, and these changes were significantly improved by APN treatment. Endometrial expressions of PPARα and HOXA10 were significantly lowered in PCOS rats and effectively up-regulated after APN treatment, but GW6471 treatment obviously blocked the effect of APN ( < 0.05). APN showed strong protective effect against PCOS-induced impairment of endometrial pinopode development, and this effect was obviously attenuated by GW6471. APN also significantly increased the pregnancy rate and embryo number in PCOS rats, while GW6471 obviously reduced the embryo number and caused developmental retardation of the embryos.
CONCLUSION
APN can improve endometrial receptivity in PCOS rats by upregulating the PARα/HOXA10 pathway.
目的
探讨过氧化物酶体增殖物激活受体α（PPARα）/同源框A10（HOXA10）信号通路在介导脂联素（APN）改善多囊卵巢综合征（PCOS）大鼠模型子宫内膜容受性中的作用。
方法
将40只来曲唑诱导的PCOS雌性SD大鼠模型随机分为4组，每组10只，另设10只正常大鼠作为对照。4组分别单独给予APN、APN联合GW6471（一种特异性PPARα抑制剂）或溶剂处理20天，PCOS模型组不做进一步处理。GW6471处理（每日剂量1mg/kg）和溶剂处理在APN处理开始后的第11天开始，均通过腹腔注射给药。观察大鼠的动情周期、体重、卵巢指数和形态、子宫指数和形态、血清激素水平及脂质代谢参数的变化。采用免疫组织化学和蛋白质印迹法检测子宫内膜中PPARα和HOXA10的表达。在电子显微镜下观察子宫内膜微绒毛的发育情况，并记录大鼠的妊娠情况。
结果
PCOS大鼠模型表现出明显的动情周期紊乱，动情间期显著延长，体重和卵巢指数增加，子宫指数降低，血清激素和脂质代谢紊乱（P<0.05），出现多囊卵巢改变，APN处理可显著改善这些变化。PCOS大鼠子宫内膜中PPARα和HOXA10的表达显著降低，APN处理后有效上调，但GW6471处理明显阻断了APN的作用（P<0.05）。APN对PCOS诱导的子宫内膜微绒毛发育损伤具有强大的保护作用，而GW6471明显减弱了这种作用。APN还显著提高了PCOS大鼠的妊娠率和胚胎数量，而GW6471明显减少了胚胎数量并导致胚胎发育迟缓。
结论
APN可通过上调PARα/HOXA10通路改善PCOS大鼠的子宫内膜容受性。
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