Premature ovarian failure (POF) is a typical form of pathological aging with complex pathogenesis and no effective treatment. Meanwhile, recent studies have reported that a high-fat and high-sugar (HFHS) diet adversely affects ovarian function and ovum quality. Here, we investigated the therapeutic effect of thymopentin (TP-5) as a treatment for murine POF derived from HFHS and its target. Pathological examination and hormone assays confirmed that TP-5 significantly improved murine POF symptoms. And, TP-5 could reduce oxidative stress injury and blood lipids in the murine POF derived from HFHS. Flow cytometry and qPCR results suggested that TP-5 attenuated activation of CD3+ T cells and type I macrophages. RNA-Seq results indicated somedifferences in gene transcription between the TP-5 intervention group and the control group. KEGG analysis indicated that the expression of genes involved in the mTOR signaling pathway was the most significantly different between the two groups. Additionally, compared with the control groups, the expression levels of interleukin, NFκB, and TNF families of genes were significantly downregulated in the POF+TP-5 group, whereas expression of the TGFβ/Smad9 genes was significantly upregulated. Finally, immunofluorescence staining and qPCR confirmed that TP-5 promoted the polarization of Mø2 cells in the ovary by activating the expression of the BMP4/Smad9 signalling pathway. Thus, our study confirmed that TP-5 has a significant therapeutic effect on POF by upregulating BMP4/Smad9 signalling pathway so as to promote the balance and polarization of immune cell and reducing the release of inflammatory factors and reduce lipid oxidative stress injury.

中文翻译：

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胸腺五肽通过减弱免疫细胞活性和促进 BMP4/Smad9 信号通路治疗小鼠卵巢早衰。

卵巢早衰（POF）是一种典型的病理衰老形式，发病机制复杂，没有有效的治疗方法。同时，最近的研究报告称，高脂肪和高糖 (HFHS) 饮食会对卵巢功能和卵子质量产生不利影响。在这里，我们研究了胸腺五肽 (TP-5) 作为治疗源自 HFHS 及其靶点的鼠 POF 的治疗效果。病理学检查和激素测定证实 TP-5 显着改善了小鼠 POF 症状。并且，TP-5可以降低HFHS衍生的小鼠POF中的氧化应激损伤和血脂。流式细胞术和 qPCR 结果表明 TP-5 减弱了 CD3+ T 细胞和 I 型巨噬细胞的活化。RNA-Seq 结果表明 TP-5 干预组和对照组之间的基因转录存在一些差异。KEGG分析表明，参与mTOR信号通路的基因表达在两组间差异最为显着。此外，与对照组相比，POF+TP-5组白细胞介素、NFκB和TNF家族基因的表达水平显着下调，而TGFβ/Smad9基因的表达水平显着上调。最后，免疫荧光染色和 qPCR 证实 TP-5 通过激活 BMP4/Smad9 信号通路的表达来促进卵巢中 Mø2 细胞的极化。因此，