Lipopolysaccharide Compromises Human Sperm Function by Reducing Intracellular cAMP

Abstract

A worldwide decline in the quality of human semen is currently occurring. In mammals, sperm are produced from diploid stem-cell spermatogonia by spermatogenesis in testes and become mature in epididymis. Nevertheless, these biological processes can be affected by Gram-negative bacterial infection mediated by lipopolysaccharide (LPS), the major endotoxin of Gram-negative bacteria. It is well known that LPS can disturb spermatogenesis and affect sperm maturation and quality in vivo. However, the effect of LPS on the ejaculated mature sperm in vitro remains unclear. Thus, this study aimed to assess the in vitro toxicity of LPS on human sperm function and to elucidate the underlying mechanism. Human sperm were incubated with LPS (0.1-100 μg/ml) for 1-12 h in vitro and, subsequently, sperm viability, motility and capacitation, and the acrosome reaction were examined. LPS dose-dependently inhibited total and progressive motility and the ability to move through a viscous medium of the sperm but did not affect sperm viability, capacitation, and the acrosome reaction. To explore the underlying mechanism of LPS's actions, we examined the effects of LPS on the intracellular concentrations of cyclic adenosine monophosphate (cAMP) and calcium ([Ca 2+ ] i ) and protein-tyrosine phosphorylation of human sperm, which are key regulators of human sperm function. LPS decreased intracellular cAMP dose-dependently but had no effect on [Ca 2+ ] i and protein-tyrosine phosphorylation of human sperm. These findings suggest that LPS inhibits human sperm motility by decreasing intracellular cAMP.

Salpingitis Impairs Bovine Tubal Function and Sperm-Oviduct Interaction

“…The molecular actions of naturally occurring inflammation in the female genital tract on sperm functional integrity have not been reported yet. However, in in vitro studies, the mechanisms of sperm damage by LPS have been attributed to mitochondrial dysfunction and activation of oxidative phosphorylation in boars 70 , cytokine release in rabbits 63 as well as to reduction of intracellular cAMP levels in humans 71 . Survival of the sperm is further compromised by morphological alterations of the ampulla induced by inflammation.…”

Effects of bacterial lipopolysaccharide on serum testosterone level and sperm vitality in mature rats

“…Therefore, leading to irreversible impairment of mitochondrial functions such as mitochondrial respiration, oxidative phosphorylation and transport (Bacon and Britton, 1990) ending with germ or Leydig's cell death. The most recent published results found that LPS decreased sperm intracellular cAMP in vitro leading to deleterious effect on sperm vitality by increasing dead sperm percent (Li et al, 2016).…”

Effects of lipopolysaccharide-induced inflammation on hypoxia and inflammatory gene expression pathways of the rat testis

“…Effects of uropathogenic bacteria and LPS in the testis include inhibition of steroidogenesis and reduced androgen production [ 18 , 19 ], decreased intracellular cAMP and reduced sperm motility [ 20 ], induction of proinflammatory cytokines and activation of antimicrobial pathways [ 10 ], and epigenetic regulation of antimicrobial gene expression [ 21 ]. However, relatively little is known about interactions between regulatory pathways and mechanisms involved in the response to inflammation of the testis.…”