Microbial Quorum-Sensing Molecules Induce Acrosome Loss and Cell Death in Human Spermatozoa

Abstract

Infertility in men and women is frequently associated with genital contamination by various commensal or uropathogenic microbes. Since many microorganisms are known to release quorum-sensing signals in substantial amounts, we raised the question whether such molecules can directly affect human spermatozoa. Here we show that farnesol and 3-oxododecanoyl-L-homoserine lactone, employed by the opportunistic pathogenic yeast Candida albicans and the gram-negative bacterium Pseudomonas aeruginosa, respectively, induce multiple damage in spermatozoa. A reduction in the motility of spermatozoa coincided in a dose-dependent manner with apoptosis and necrosis at concentrations which were nondeleterious for dendritic cell-like immune cells. Moreover, sublethal doses of both signaling molecules induced premature loss of the acrosome, a cap-like structure of the sperm head which is essential for fertilization. Addressing their mechanism of action, we found that the bacterial molecule, but not the fungal molecule, actively induced the acrosome reaction via a calciumdependent mechanism. This work uncovers a new facet in the interaction of microorganisms with human gametes and suggests a putative link between microbial communication systems and host infertility.

Apoptotic sperm biomarkers and their correlation with conventional sperm parameters and male fertility potential

“…Furthermore, we have found a highly significant negative correlation between FSH and viable sperm with normal MMP, which confirms the findings by Ruwanpura et al [36], obtained in experimental conditions. Similarly, the changes in MMP already observed in cases of inflammation [9,35,40,47] were correlated with FSH, the main hormonal regulator of spermatogenesis; however, this relation did not exist with DNA denaturation, which is in agreement with the findings of Appasamy et al [1]. We have observed a highly significant correlation between dead, apoptotic and viable sperm, viable sperm with normal MMP, sperm with DNA denaturation and conventional sperm parameters, which is in agreement with the findings in the literature [3,6,27,41].…”

Farnesol Induces Hydrogen Peroxide Resistance in Candida albicans Yeast by Inhibiting the Ras-Cyclic AMP Signaling Pathway

“…Farnesol has been previously shown to be poisonous to bacteria, fungi, and mammalian cells (4,27,37,47,54,56). In contrast, farnesol toxicity for C. albicans is conditional (31), and several studies report a complete absence of lethality (10,26,45).…”

Quorum sensing in fungi – a review

“…Farnesol also inhibited murine macrophage antifungal activity against C. albicans by inducing oxidative stress and apoptosis of macrophages [33]. Finally, farnesol induced apoptosis and necrosis of human spermatozoa suggesting a possible link between microbes and host infertility [35]. Thus, farnesol seems to play multiple roles during infection both as a QSM and as a virulence factor per se.…”