Comparative proteomics reveals protective effect of resveratrol on a high-fat diet-induced damage to mice testis.

In recent years, resveratrol has been shown to protect against metabolic damage, including obesity-associated subfertility/infertility. In the present study, proteomic alterations in testicular tissues were investigated by tandem mass tag (TMT) in mice fed with a high-fat diet (HFD) without or with resveratrol supplementation (HFD+RSV). Serum testosterone levels, spermatozoa parameters and testicular histological morphology were assessed. Resveratrol treatment was shown to significantly reduce serum cholesterol, prevent the HFD-induced reductions in serum testosterone and spermatozoa parameters, and decrease the ultrastructural degeneration of testicular tissues. The comparative proteomics analysis revealed 58 differentially expressed proteins between the HFD and control groups and 38 differentially expressed proteins between the HFD and HFD+RSV groups. Gene ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the most highly enriched differential proteins were correlated to spermatozoa function and cholesterol metabolism. The real-time RT-PCR and western blotting results confirmed the differential expression of the corresponding proteins related to spermatozoa function that were identified by proteomics. The present study provides new insight into the mechanisms of the beneficial effects of resveratrol, and may present it as a potential therapeutic strategy for obesity-associated male subfertility/infertility.Abbreviations:TMT: Tandem mass tag; HFD: High-fat diet; RSV: Resveratrol; GO: Gene ontology; Protein-proteinKEGG: Kyoto Encyclopedia of Genes and Genomes; RT-PCR: Reverse transcription-polymerase chain reaction; SDS-PAGE: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis; PVDF: Polyvinylidene fluoride; ECL: Enhanced chemiluminescence; RIPA: Radio-immunoprecipitation assay; CTRL: Control; PPI: interaction; RIA: Radioimmunoassay; T: Testosterone; TG: Triglycerides; TC: Total cholesterol; LDL-c: Low-density lipoprotein cholesterol; HDL-c: High-density lipoprotein cholesterol; Crisp1: Cysteine-rich secretory protein 1; SIRT1: Sirtuin 1; GPx5: Glutathione peroxidase 5; Svs4: Seminal vesicle secretory protein 4; Tssk3: Testis-specific serine kinase 3; Pate4: Prostate and testis expressed 4; Sva: Seminal vesicle antigen; Lcn5: Lipocalin 5; Spinkl: Serine protease inhibitor, Kazal type-like.

Melatonin appears to protect against steroidogenic collapse in both mice fed with high-fat diet and H2 O2 -treated TM3 cells.

High-fat diets (HFDs) are detrimental to steroidogenesis and male fertility. This study aimed to investigate the protective effects of melatonin (MT) treatment on testicular dysfunction in mice fed with HFD. C57BL/6J male mice were randomly divided into three groups: CTRL, HFD and HFD + MT. MT treatment mitigated the increase in body weight and adipose tissue in HFD-fed mice. Serum levels of sex hormones were improved upon MT supplementation, and the expression of the testosterone synthesis proteins, StAR and P450scc was rescued as well. MT treatment significantly up-regulated the expression of SIRT1, SOD2, and GPx4 and down-regulated the expression of GRP78 and CHOP, indicating an attenuation of oxidative stress (OS) and endoplasmic reticulum (ER) stress. In TM3 cells, MT treatment protected against H2 O2 -induced steroidogenic collapse by improving mitochondrial function and attenuating OS and ER stress. These results indicate that MT treatment can improve steroidogenesis in mice fed with HFD and may have therapeutic value in the treatment of obesity-associated hypogonadism.