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.

Nutritional modifications in male infertility: a systematic review covering 2 decades

“…96 Cholesterol-rich diets have the potential to contribute to male infertility and to decrease semen quality via disruption of the blood-testes barrier. 34 The blood-testes barrier, a structure consisting of tight junctions between Sertoli cells, limits the entry of toxins into the seminiferous tubules. 97 During spermatogenesis, the blood-testes barrier undergoes rapid assembly and disassembly of tight junctions due to regulation of protein trafficking.…”

“…97 During spermatogenesis, the blood-testes barrier undergoes rapid assembly and disassembly of tight junctions due to regulation of protein trafficking. 98,99 Since uptake of extracellular cholesterol in Sertoli cells occurs via endocytosis, elevated plasma cholesterol is thought to promote endocytic accumulation of tight-junction proteins in Sertoli cells and disrupt the integrity of the blood-testes barrier, thereby contributing to impaired spermatogenesis 34 ( Figure 3). This review benefits from several strengths, including its systematic and exhaustive approach, its use of the American Dietetic Association's quality checklist, and its methodological rigor.…”

“…In another animal study, Bakos et al 40 reported that paternal-diet-induced obesity decreased both the motility and the fertilizing ability of sperm in male mice. Morgan et al 34 also reported that elevated levels of plasma cholesterol induced by a cholesterol-rich diet negatively affected spermatogenesis in rabbits. To date, many human studies have investigated semen quality and male infertility, but most of these focus on isolated micronutrients (such as different antioxidants, zinc, or folate), while studies of a specific diet or food compound are scarce.…”

“…[27][28][29][30] Recent evidence from both animal and human studies indicates that male obesity and high-fat diets result in impaired reproductivity, affecting the molecular and physical structure of sperm as well as the health of the developing fetus and subsequent offspring. 27,[31][32][33][34][35][36][37][38][39] In a recent animal study, Rato et al 39 reported that the testicular physiology is sensitive to alterations of whole-body metabolism and that the testicular metabolism can be disturbed by high-energy diets. Disruption of testicular metabolism is associated with decreased sperm quality.…”

Biochemical and seminal parameters of lambs fed palm kernel cake under grazing system

“…Moreover, dietary polyunsaturated fatty acids (PUFA) enhance energy density and optimize reproductive parameters in male sheep. However, high levels of cholesterol in animals and higher accumulation in Sertoli cells may thereby reduce normal and physiologycal testicular function, decrease sperm concentration, impair sperm motility, and undervalue the male fertility (Fair et al, 2014;Morgan et al, 2014).…”