title: Palmitoyl-protein thioesterase 1 (PPT1): an obesity-induced rat testicular marker of reduced fertility.
abstract: Male obesity may lead to declines in testosterone levels, reproductive hormonal profile, and semen quantity. To assess the effects of obesity on spermatogenesis, Sprague-Dawley rats fed a high-fat diet served as a model of induced obesity. The litter sizes for females mated to obese males were significantly lower as compared to females mated with normal-diet-fed controls. Their serum high-density lipoprotein, low-density lipoprotein, cholesterol, and estradiol levels increased in obese males, but testosterone and follicle-stimulating hormone levels decreased. Testicular morphology disruptions included Sertoli-cell atrophy, disrupted tight junctions, and mitochondrial degeneration in spermatogenic cells. To further investigate the molecular mechanisms leading to high-fat-diet-induced changes, we employed testicular proteomic analysis on rats fed both types of diet. Three spots were up-regulated in rats fed a high-fat diet whereas two others were downregulated. One of the upregulated spots was palmitoyl-protein thioesterase 1 (PPT1), a lipoprotein metabolizing related enzyme localized to Sertoli cells. In a Sertoli-cell line cultured in a high-fat supplemented medium, PPT1 abundance was accompanied by increases in the endocytic vesicle-associated protein, clathrin, and decreases in the tight junctional proteins, ZO-1 and occludin. In conclusion, declines in rat male fertility induced by a high-fat diet are associated with an altered testicular protein expression pattern as well as disruption of testicular Sertoli-cell and spermatogenic-cell morphology. PPT1 expression may provide a testicular marker of reduced fertility in obese males, as increases in its expression may be detrimental to Sertoli-cell function during spermatogenesis.
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.forename: Wenzhen
authors.initials: W
authors.lastname: Zhao
authors.forename: Guobao
authors.initials: G
authors.lastname: Gu
authors.forename: Liming
authors.initials: L
authors.lastname: Lu
authors.forename: Jingsheng
authors.initials: J
authors.lastname: Feng
authors.forename: Qiangsu
authors.initials: Q
authors.lastname: Guo
authors.forename: Zhide
authors.initials: Z
authors.lastname: Ding
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001835:Body Weight; D017931:DNA Primers / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional; D005455:Fluorescent Antibody Technique; D005640:Follicle Stimulating Hormone / Q000097:blood; D005786:Gene Expression Regulation / Q000502:physiology*; D007248:Infertility, Male / Q000209:etiology / Q000503:physiopathology*; D008074:Lipoproteins / Q000097:blood; D008098:Litter Size / Q000502:physiology; D008297:Male; D013058:Mass Spectrometry; D009765:Obesity / Q000150:complications / Q000503:physiopathology*; D062793:Occludin / Q000378:metabolism; D020543:Proteome / Q000378:metabolism; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012708:Sertoli Cells / Q000502:physiology; D013091:Spermatogenesis / Q000502:physiology*; D013737:Testis / Q000378:metabolism / Q000473:pathology*; D013739:Testosterone / Q000097:blood; D013869:Thiolester Hydrolases / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D015415:Biomarkers; D017931:DNA Primers; D008074:Lipoproteins; D062793:Occludin; D020543:Proteome; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D013739:Testosterone; D005640:Follicle Stimulating Hormone; D013869:Thiolester Hydrolases; C095299:palmitoyl-protein thioesterase