Effects of high-fat diet on testicular germ cell apoptosis in mice through endoplasmic reticulum stress

Ben-wen Zhou; Chang-cheng Zhang; He Deng; Si-min Chen; Yan-yu Chang; Yan-na Yang; Guo-qing FU; Ding Yuan; Hai-xia Zhao; Ben-wen Zhou; He Deng; Yan-na Yang; Hai-xia Zhao; Ben-wen Zhou; Chang-cheng Zhang; Si-min Chen; Yan-yu Chang; Guo-qing FU

Return

Effects of high-fat diet on testicular germ cell apoptosis in mice through endoplasmic reticulum stress

Author: Ben-Wen ZHOU ¹ ; Chang-Cheng ZHANG ¹ ; He DENG ¹ ; Si-Min CHEN ¹ ; Yan-Yu CHANG ¹ ; Yan-Na YANG ¹ ; Guo-Qing FU ¹ ; Ding YUAN ¹ ; Hai-Xia ZHAO ¹ ; Ben-Wen ZHOU ² ; He DENG ² ; Yan-Na YANG ² ; Hai-Xia ZHAO ² ; Ben-Wen ZHOU ³ ; Chang-Cheng ZHANG ³ ; Si-Min CHEN ³ ; Yan-Yu CHANG ³ ; Guo-Qing FU ³
Author Information

1. Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, China Three Gorges University, State Administration of Traditional Chinese Medicine,
2. College of Basic Medical Science, China Three Gorges University
3. College of Medicine and Health Science, China Three Gorges University
Publication Type:Journal Article
Keywords: apoptosis; endoplasmic reticulum stress; germ cells; high-fat diet; testis; unfolded protein response
From: Chinese Pharmacological Bulletin 2023;39(12):2346-2353
CountryChina
Language:Chinese
Abstract: Aim To study the effects of high-fat diet on testicular germ cell apoptosis in mice through endoplasmic reticulum stress. Methods C57BL/6J male mice were assigned into normal group and high-fat diet group randomly, with six mice in each group. The mice in normal group or high-fat diet group were fed with regular or high-fat diet continuously for five months. The mice were weighed, anesthetized, and euthanized to collect testicular and epididymal tissue for analysis. The testicular tissue was weighed and their indices were calculated. Epididymal tissue was collected for semen analysis. The morphological alterations of testicular tissue were observed using hematoxylin-eosin ( HE ) staining. The apoptosis of germ cells was detected by TUNEL staining and the apoptotic indices were calculated. The expression levels of apoptosis and endoplasmic reticulum stress-related proteins in testicular tissue were detected by Western blot. The protein expression and localization of GRP78 in testicular tissue were further detected by immunofluorescence. Results The results showed that compared to the normal group, the high-fat diet group had a significant increase in body weight, a significant decrease in testicular index, sperm concentration, and sperm vability, loose arrangement of germ cells, significant thinning of the seminiferous epithelium, no significant change in the diameter of seminiferous tubules, a significant increase in germ cell apoptosis , with an increased apoptosis index, and significant increase in expression of Bax and cleaved-caspase-12,and a significant decrease in Bcl-2 protein expression. The expression levels of GRP78 , p-IREl, XBP1, and ATF6a proteins were significantly up-regulated, while p-PERK, p-eIF2a, ATF4 protein expression showed no significant changes. Immunofluorescence results further showed a significant increase in the expression of GRP78 protein in the testicular tissue,with no significant changes in the expression location. Conclusions High-fat diet can induce the apoptosis of mouse testicular germ cells, and the mechanism may be related to the activation of endoplasmic reticulum stress IRE1 and ATF6 signaling pathway.