title: Cholesterol-enriched diet disrupts the blood-testis barrier in rabbits.
abstract: About 15% of heterosexual couples in the USA suffer from infertility issues; male infertility accounts for ∼50% of all infertility cases and roughly 50% of male infertility is idiopathic. Increased levels of plasma cholesterol affect spermatogenesis and male fertility negatively, but by unclear mechanisms. Clearly, spermatogenesis occurs in immune-privileged seminiferous tubules that are protected by the blood-testis barrier (BTB), and BTB disruption results in sperm damage and male infertility. Accordingly, using rabbits fed a 2% cholesterol-enriched diet for 2, 4, and 6 wk to raise levels of plasma cholesterol, we tested the hypothesis that elevated levels of plasma cholesterol disrupt the BTB functionally and biochemically. The cholesterol-enriched diet increased lipid deposition dramatically and time-dependently in the seminiferous tubules and disrupted the BTB as evidenced by increased IgG staining within the seminiferous tubules. Total protein levels of the tight-junction proteins ZO-1 and occludin were increased in the seminiferous tubules of rabbits fed the cholesterol-enriched diet, and the distribution patterns of tight-junction proteins were markedly affected, including an increased accumulation of tight-junction proteins in endosomes. Disruption of the integrity of the BTB due to increased plasma levels of cholesterol might play a role in male infertility.
authors.affiliation: Department of Basic Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Morgan
authors.affiliation: Department of Basic Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota.
authors.forename: Othman
authors.initials: O
authors.lastname: Ghribi
authors.affiliation: Department of Basic Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota.
authors.forename: Liang
authors.initials: L
authors.lastname: Hui
authors.affiliation: Department of Basic Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Geiger
authors.affiliation: Department of Basic Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota xuesong.chen@med.und.edu.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D001814:Blood-Testis Barrier / Q000187:drug effects* / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D059305:Diet, High-Fat; D007248:Infertility, Male / Q000209:etiology / Q000378:metabolism; D008297:Male; D011817:Rabbits; D012671:Seminiferous Tubules / Q000187:drug effects / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism
chemical_list: D002791:Cholesterol, Dietary
keywords: blood-testis barrier; cholesterol; male infertility; tight junctions