Can apoptosis and necrosis coexist in ejaculated human spermatozoa during in vitro semen bacterial infection?

Abstract

The cellular death observed in spermatozoa in the presence of inflammatory mediators may be due to both apoptosis and necrosis. Here, we demonstrate for the first time that direct contact of conditionally pathogenic bacteria with ejaculated human sperm may play an even greater role in the promotion of apoptosis than in case of some pathogenic bacterial strains. These findings suggest that significant bacteriospermia and leukocytospermia may be direct causes of subfertility or additional negative factors worsening the prognosis of fertility in natural and assisted procreation.

Mechanisms of the harmful effects of bacterial semen infection on ejaculated human spermatozoa: potential inflammatory markers in semen

“…In another experimental study, the loss of sperm motility induced by the soluble products of E. coli was accompanied by the increased intrinsic mitochondrial generation of ROS and membrane lipid peroxidation [8]. In line with these findings, our original experimental data have demonstrated a direct role for conditionally pathogenic bacterial strains, S. haemolyticus and B. ureolyticus, in the induction of sperm apoptosis, as reflected by reductions in sperm motility, mitochondrial depolarization, lipid peroxidation, loss of sperm membrane asymmetry, PS externalization, and DNA fragmentation with subsequently reduced competence of sperm-oocyte fusion [9,31]. All the above data have provided molecular evidence for the induction of sperm death by distinct bacterial agents (differing in pathogenicity and metabolism), partially due to intrinsic apoptotic cascade.…”

“…Our data have demonstrated that, during experimental semen infection in vitro, ejaculated human spermatozoa exhibited reduced viability visible in HOS tests and increased proportions of dead sperm [9]. However, DNA fragmentation was observed in both apoptotic and necrotic sperm, and the most part of the latter [31]. This is in agreement with the ultrastructural findings of Collodel et al [110], who observed a high percentage of sperm with anomalies typical of apoptosis, as well as of necrosis, from individuals affected by urogenital bacterial infection, although the percentage of necrotic sperm was predominant in the majority of infected semen samples.…”

“…Most probably, the monitoring of a complex network of molecular, biochemical, immunological, oxidative, and inflammatory parameters in semen may offer a chance to better understand the mechanisms leading to subfertility and infertility caused or complicated by microbial infection of the semen. The value of such observations would be significant, [9,10,31,39,51]. (1) Bacteria and their toxins trigger the infiltration of immune cells connected with (2) the production and release of large amounts of ROS (neutrophils, macrophages) as well as (3) immune regulatory factors (from macrophages, lymphocytes, monocytes, and dendritic cells); the cytokines may modulate the activities of the prooxidative and antioxidative systems, which may also result in the enhanced secretion of ROS; (4) When the amounts of ROS exceed the potential of the antioxidative defence, oxidative stress occurs; (5) Oxidative stress induces lipid sperm membrane peroxidation and leads to a series of detrimental defects in the spermatozoa, including lipid asymmetry loss, motility loss, PS externalization, and loss of ∆Ψm.…”

“…There are strong premises that the direct contact of bacteria and their toxins with spermatozoa is an initial signal for germ cell death. This is evidenced by experimental reports in which different types of bacterial strains directly increased apoptotic features in ejaculated human spermatozoa, without the mediation of external ROS generated by leukocytes [11,31]. The proapoptotic effect of bacteria on sperm may mostly or at least partially be the consequence of bacterial endotoxins, including LPS, porins, and peptidoglycans via Toll-like receptors (TLR) 2 and 4, of which expression in the membranes of human spermatozoa has been demonstrated [108].…”

The impact of Corynebacterium glucuronolyticum on semen parameters: a prospective pre–post‐treatment study

“…The question then remains what are the underlying pathophysiological mechanisms that result in reduced semen parameters and (in the worst‐case scenario) give rise to infertility. Some authors concentrate only on the induction of necrosis and apoptosis (Fraczek et al ., ), while others propose the putative role of antigenic mimicry that may exist between certain components of spermatozoa and bacterial proteins (Moretti et al ., ). Although thus far such cross‐reaction has been proved only for the flagella of spermatozoa by Moretti et al .…”