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糖尿病对 Db/Db 小鼠模型精子质量的影响及 FoxO1 通路的作用。

Effects of Diabetes Mellitus on Sperm Quality in the Db/Db Mouse Model and the Role of the FoxO1 Pathway.

机构信息

First Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China (mainland).

Department of Andrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China (mainland).

出版信息

Med Sci Monit. 2021 Feb 16;27:e928232. doi: 10.12659/MSM.928232.

DOI:10.12659/MSM.928232
PMID:33589581
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7896429/
Abstract

BACKGROUND Studies have shown that diabetes mellitus (DM) has a negative impact on male reproductive function, which may lead to changes in the testis and epididymis and a decline in semen quality. MATERIAL AND METHODS We performed animal experiments with 6 diabetic db/db mice as the model group (group B) and 6 C57BL/6J mice as the control group (group A). After adaptive feeding for 7 days, the sperm quality of each group was measured. Concurrently, the morphology of the mouse testis was observed by hematoxylin-eosin (H&E) staining. The expression of the PI3K, Akt, FoxO1, FasL, IL-6, and Stat3 proteins and mRNAs in the testicular tissue was detected by western blotting and RT-qPCR. RESULTS The number of spermatozoa and sperm motility of group A was significantly higher than that of group B (P<0.05). H&E staining of the testicular tissue showed the seminiferous tubules in group B mice were damaged to varying degrees and the seminiferous tubules were sparsely arranged. Compared with those of group A, the expression levels of PI3K, Akt, and Stat3 proteins and mRNAs in group B were significantly lower (P<0.05), while the expression levels of FoxO1, FasL, and IL-6 proteins and mRNAs in group B mice were significantly higher (P<0.05). CONCLUSIONS This study demonstrated that DM inhibited the expression of PI3K, Akt, and Stat3 proteins and mRNAs in the FoxO1 pathway and promoted the expression of FoxO1, FasL, and IL-6 proteins and mRNAs, leading to abnormal apoptosis of testicular tissue cells and functional damage, and eventually spermatogenic dysfunction.

摘要

背景

研究表明,糖尿病(DM)对男性生殖功能有负面影响,可能导致睾丸和附睾发生变化,精液质量下降。

材料和方法

我们进行了动物实验,使用 6 只糖尿病 db/db 小鼠作为模型组(B 组)和 6 只 C57BL/6J 小鼠作为对照组(A 组)。适应喂养 7 天后,测量每组的精子质量。同时,通过苏木精-伊红(H&E)染色观察小鼠睾丸的形态。通过 Western blot 和 RT-qPCR 检测睾丸组织中 PI3K、Akt、FoxO1、FasL、IL-6 和 Stat3 蛋白和 mRNA 的表达。

结果

A 组的精子数和精子活力明显高于 B 组(P<0.05)。B 组小鼠睾丸组织 H&E 染色显示,生精小管受损程度不同,生精小管排列稀疏。与 A 组相比,B 组 PI3K、Akt 和 Stat3 蛋白和 mRNA 的表达水平明显降低(P<0.05),而 FoxO1、FasL 和 IL-6 蛋白和 mRNA 的表达水平明显升高(P<0.05)。

结论

本研究表明,DM 抑制 FoxO1 通路中 PI3K、Akt 和 Stat3 蛋白和 mRNA 的表达,促进 FoxO1、FasL 和 IL-6 蛋白和 mRNA 的表达,导致睾丸组织细胞异常凋亡和功能损伤,最终导致生精功能障碍。

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