Cholesterol-enriched diet disrupts the blood-testis barrier in rabbits

Am J Physiol Endocrinol Metab. 2014 Dec 15;307(12):E1125-30. doi: 10.1152/ajpendo.00416.2014. Epub 2014 Oct 21.

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.

Keywords: blood-testis barrier; cholesterol; male infertility; tight junctions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Testis Barrier / drug effects*
  • Blood-Testis Barrier / metabolism
  • Cholesterol, Dietary / administration & dosage*
  • Diet, High-Fat*
  • Infertility, Male / etiology
  • Infertility, Male / metabolism
  • Male
  • Rabbits
  • Seminiferous Tubules / drug effects
  • Seminiferous Tubules / metabolism
  • Tight Junctions / drug effects
  • Tight Junctions / metabolism

Substances

  • Cholesterol, Dietary