PPAR-γ激动剂吡格列酮通过调节PPAR-γ/Wnt5/β-catenin通路改善薄内膜大鼠子宫内膜容受性,逆转子宫内膜屏障破坏,促进卵巢功能

IF 2.9 3区 医学 Q3 IMMUNOLOGY
Heqiao Li , Yu Guan , Xinru Chen , Wenfan Tian , Jinghong Xie , Bin Yang
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引用次数: 0

摘要

薄型子宫内膜(TE)是一种常见的生殖内分泌疾病,PPAR-γ已被报道通过Wnt5/β-catenin通路调控细胞增殖和串扰。然而,PPAR-γ是否促进子宫内膜上皮细胞增殖并通过Wnt5/β-catenin途径起作用尚未探索。建立大鼠子宫内膜变薄模型,给药15 d, HE染色观察子宫和卵巢形态学变化。采用酶联免疫吸附试验(ELISA)检测血清性激素水平。电镜观察子宫内膜表面形态。免疫组化法检测子宫内膜容受性蛋白、子宫内膜屏障蛋白和卵巢功能蛋白的表达。通过分子对接和Western blotting分析PPAR-γ/Wnt5/β-catenin通路的激活情况。结果显示,PIO改善了TE大鼠子宫内膜形态、内膜厚度、腺体数量和子宫内膜耐受相关蛋白的表达,促进了子宫内膜屏障的修复。血清激素水平、成熟卵泡和黄体数量增加,表明卵巢功能改善。western blot结果显示,PIO下调Wnt5/β-catenin信号通路,增加卵巢内分泌相关蛋白的表达。我们的研究结果表明,PPAR-γ激动剂吡格列酮通过上调PPAR-γ的表达抑制Wnt5/β-catenin通路,促进上皮细胞增殖和子宫内膜屏障修复,在治疗TE的同时起到保护卵巢功能的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
PPAR-gamma agonist pioglitazone improves endometrial receptivity, reverses endometrial barrier disruption and promotes ovarian function in thin endometrium rats via modulation PPAR-γ/Wnt5/β-catenin pathway
Thin endometrium (TE) is a common reproductive endocrine disorder, PPAR-γ has been reported to regulate cell proliferation and crosstalk with the Wnt5/β-catenin pathway. However, whether PPAR-γ promotes endometrial epithelial cell proliferation and acts through the Wnt5/β-catenin pathway has not been explored. A rat model of endometrial thinning was established and administered for 15 days, and the morphology of the uterus and ovaries was observed by HE staining. Serum sex hormone levels were measured by enzyme-linked immunosorbent assay (ELISA). The morphology of endometrial surface was observed by electron microscopy. Immunohistochemistry was used to detect the expression of endometrial receptivity, endometrial barrier and ovarian function proteins. Activation of PPAR-γ/Wnt5/β-catenin pathway was analyzed by molecular docking and Western blotting. The results showed that PIO improved endometrial morphology, endometrial thickness, gland number and expression of endometrial tolerance-related proteins, and promoted the repair of endometrial barrier in TE rats. Serum hormone levels, mature follicle and corpus luteum numbers were increased, indicating improved ovarian function. PIO downregulated the Wnt5/β-catenin signaling pathway and increased the expression of ovarian endocrine-related proteins, as shown by western blot analysis. Our findings revealed that thr PPAR-γ agonist pioglitazone inhibited the Wnt5/β-catenin pathway by up-regulating the expression of PPAR-γ and promoted the proliferation of epithelial cells and the repair of the endometrial barrier, which played a role in protecting ovarian function while treating TE.
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来源期刊
CiteScore
6.30
自引率
5.90%
发文量
162
审稿时长
10.6 weeks
期刊介绍: Affiliated with the European Society of Reproductive Immunology and with the International Society for Immunology of Reproduction The aim of the Journal of Reproductive Immunology is to provide the critical forum for the dissemination of results from high quality research in all aspects of experimental, animal and clinical reproductive immunobiology. This encompasses normal and pathological processes of: * Male and Female Reproductive Tracts * Gametogenesis and Embryogenesis * Implantation and Placental Development * Gestation and Parturition * Mammary Gland and Lactation.
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