Bacterial infections cause sperm dysfunction through their outer membrane vesicles

Infertility rates continue to rise worldwide and are currently estimated to affect up to 170 million people. Male factors contribute to at least half of all infertility cases, including hormonal abnormalities, problems with sperm transport or entry into the fallopian tubes, altered sperm production, and male reproductive tract infections ( MRTI)

MRTIs are responsible for approximately 10% of cases of male infertility. A new pathogen study discusses the impact of Escherichia coli (E. coli) infection on sperm parameters.

Study: Impact of vesicles on the outer membrane of Escherichia coli on sperm function. Image credit: SciePro / Shutterstock.com

Introduction

Most MRTIs are caused by bacteria such as Staphylococcus epidermidis, Streptococcus viridans, Staphylococcus aureus, Enterococcus faecalis and E. coli. In fact, E. coli accounts for 65-80% of bacterial prostatitis, mostly O1, O2, O4, and O6 serotypes.

E. coli negatively affects the functions of sperm that are essential for fertilization of the egg to form a zygote. This may include a reduction in sperm motility as gametes clump together after contact with sugar residues on the cell surface of these bacteria, primarily in type 1 and P fimbriae.

With P-type fimbriae, exposed galactosyl residues found throughout the sperm cause end-to-tail agglutination. Comparatively, in type 1 fimbriae, the heads of adjacent spermatozoa bind through mannose residues to the surface of this spermatic component.

Another cause of immobilization or reduced motility of sperm is decreased mitochondrial membrane potential when bacteria counteract. The result of these interactions is damage to the sperm head, impaired acrosome integrity, disruption of the acrosome reaction, and cell death. In addition, an increase in reactive oxygen species (ROS) such as superoxide ions will also cause damage to lipid membranes and genetic material.

The current study examines the effects after sperm exposure on outer membrane vesicles (OMV) to E. coli. OMVs are spherical structures with nanoscale diameters and are bounded by lipid bilayers that include lipopolysaccharides, phospholipids, and proteins found in outer membranes.

OMVs also contain cytoplasmic material and adjacent cellular areas, such as genetic material, as well as virulence factors such as invasion proteins, escape proteins, and bacterial toxins.

OMVs are involved in protective functions, such as obtaining nutrients and forming insulating biofilms to evade and resist immune attack, as well as transfer genes, while helping the pathogen to achieve entry and infection. host. These vesicles also provide toxins, adhesins, and immunomodulators to the host cell.

Taken together, the researchers in the current study determined the mechanisms by which exposure to VMOs would affect sperm function in vitro. These findings are expected to aid in the development of effective strategies to minimize MRTI damage.

Study results

OMVs with an average diameter of approximately 100 nm were obtained from E. coli cultures. coli and were purified. OMVs were subsequently added to purified sperm for periods of time ranging from 30 to 90 minutes. The effects on sperm motility, viability, and shape were then evaluated.

The viable percentage and morphology of the sperm did not vary; however, motility was normal in only half of the exposed sperm compared with 65% of controls, with the remaining immobile sperm. Sperm function decreased after exposure to OMV for 45 minutes.

After one hour, sperm motility decreased by more than 10%, while at 1.5 hours, the percentages of mobile and immobile sperm were about 40% and 60%, respectively. In contrast, motility remained at 60% at controls at this time.

Exposure to OMV also caused ROS to form and accumulate in the neck region of sperm over time, with the first significant elevation reaching 18% after 45 minutes. At one hour and 90 minutes, ROS levels were almost 40% higher, which was approximately twice that of the control group and equivalent to that of benzene-treated sperm.

Sperm DNA damage also occurred and increased with time to treatment. Beginning with damage to more than a quarter of sperm at 45 minutes and a DNA fragmentation rate (DFI) of 27%, DNA damage subsequently outweighed that of positive control sperm in a 15% in one hour and finally reached the maximum at 1.5 hours. At this point, nearly 40% of sperm exposed to OMV had DNA fragmentation, which was double the proportion of untreated sperm.

Implications

The results of the study indicate that OMVs, which are produced by many pathogenic bacteria such as E. coli, play an important role in the disease process by mediating bacterial virulence. Here, the effects of OMVs on human sperm are first reported and appear to reduce sperm function as a result of impaired motility and DNA damage.

Interestingly, no alterations for sperm morphology or viability were described. Morphological changes may have been masked by the superficial binding of OMVs, as these vesicles bind to surface receptors to activate signaling pathways.

Other researchers have observed that apoptosis of sperm occurs one hour after exposure to E. coli. However, this is not necessarily contradictory, as the current study may have used too low a concentration of OMV for too short an exposure time to cause observable sperm death.

The accumulation of ROS is associated with rapid oxidative stress and causes lipid peroxidation of the sperm membrane. Subsequently, sperm motility is reduced through various mechanisms, such as loss of sperm flexibility, disruption of cellular processes that contribute to motility, and mitochondrial damage as a result of ROS-bound reduction of triphosphate. of adenosine (ATP), which provides energy for motility.

DNA damage also occurred as a result of exposure to OMV and was probably due to ROS, which caused chain breaks, cross-links, and chromosomal rearrangements. The apoptotic processes associated with ROS could also contribute to this result.

Subsequent research will provide a more detailed description of the pathogenesis of sperm injury due to OMVs.

Magazine reference:

  • Folliero, V., Santonastaso, M., Dell’Annunziata, F., et al. (2022). Impact of vesicles on the outer membrane of Escherichia coli on sperm function. Pathogens. doi: 10.3390 / pathogens11070782.

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