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 infertility cases, including hormonal abnormalities, problems with sperm transport or entry into the fallopian tubes, impaired sperm production, and male reproductive tract infections (MRTIs).
MRTIs are responsible for about 10% of male infertility cases. New Pathogens the study discusses the impact Escherichia coli (E-coli) infection on sperm parameters.
Studies: Effect of Escherichia coli outer membrane vesicles on sperm function. Image credit: SciePro / Shutterstock.com
Most MRTIs are caused by bacteria including Staphylococcus epidermidis, Streptococcus viridans, Staphylococcus aureus, Enterococcus faecalis, and E-coli. Actually, E-coli they make up 65-80% of bacterial prostatitis, mostly serotypes O1, O2, O4 and O6.
E-coli adversely affects the functions of sperm, which are necessary for fertilization of the egg to form a zygote. This may include reduced sperm motility as the gametes agglutinate upon contact with sugar residues on the cell surface of these bacteria, mainly on fimbriae of type 1 and P.
In P-type fimbriae, exposed galactosyl residues found throughout sperm cause head-to-tail agglutination. In contrast, on type 1 fimbriae, the heads of neighboring sperm attach via mannose residues on the surface of this sperm component.
Another cause of sperm immobilization or reduced motility is the reduced potential of the mitochondrial membrane when acting against bacteria. 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 investigates the effects after exposure of sperm to outer membrane vesicles (OMVs) in E-coli. OMVs are nanoscale spherical structures and are bounded by lipid bilayers including lipopolysaccharides, phospholipids, and proteins found in outer membranes.
OMVs also contain material from the cytoplasm and adjacent cellular regions, such as genetic material, in addition to virulence factors such as invasion proteins, escape proteins, and bacterial toxins.
OMVs are involved in protective functions such as acquiring nutrients and forming insulating biofilms to evade and resist immune attack, as well as transfer genes, while also helping the pathogen to achieve host entry and infection. These vesicles also deliver toxins, adhesins, and immunomodulators to the host cell.
Taken together, the researchers of the current study determined the mechanisms by which OMV exposure would affect sperm function in vitro. These findings are expected to aid in the development of effective counterstrategies to minimize MRTI damage.
OMVs with a mean diameter of approximately 100 nm were obtained from E-coli cultures and purified. OMVs were then added to the purified spermatozoa for 30 to 90 minutes. Effects on sperm motility, viability and shape were then assessed.
Viable percentage and sperm morphology did not change; however, motility was normal in only half of the exposed sperm compared to 65% of the controls, with the remaining sperm being non-motile. Sperm function decreased after exposure to OMV for 45 minutes.
After one hour, sperm motility decreased by more than 10%, while after 1.5 hours, the percentage of motile and immotile sperm was approximately 40% and 60%, respectively. Conversely, motility remained at 60% of controls at this time point.
OMV exposure also caused the generation and accumulation of ROS in the sperm neck region over time, with the first significant increase reaching 18% at 45 min. After one hour and 90 minutes, ROS levels were nearly 40% higher, which was about twice that of the control group and equivalent to levels in benzene-treated sperm.
There was also sperm DNA damage that increased with treatment time. Starting with damage to more than a quarter of sperm at 45 minutes and a DNA fragmentation index (DFI) of 27%, DNA damage subsequently exceeded that of positive control sperm by 15% at one hour and finally peaked at 1.5 hours. At this point, nearly 40% of OMV-exposed sperm showed DNA fragmentation, which was double the proportion of untreated sperm.
The results of the study indicate that OMVs, which are produced by many pathogenic bacteria, like E-coli, have a significant role in the disease process by mediating bacterial virulence. This paper describes for the first time the effects of OMVs on human sperm and appears to reduce sperm function through impaired motility and DNA damage.
Interestingly, no changes in sperm morphology or viability were reported. Morphological changes may have been masked by surface binding of OMVs, as these vesicles bind to surface receptors to activate signaling pathways.
Other researchers have observed sperm apoptosis occurring one hour after exposure E-coli. However, this is not necessarily inconsistent, as the current study may have used too low a concentration of OMV for too short an exposure time to cause observable sperm death.
ROS accumulation is associated with rapid oxidative stress and causes sperm membrane lipid peroxidation. Sperm motility is subsequently reduced through several mechanisms, including loss of sperm flexibility, disruption of cellular processes that contribute to motility, and mitochondrial damage due to ROS-mediated reduction of adenosine triphosphate (ATP), which provides energy for motility.
DNA damage also occurred as a result of OMV exposure and was likely caused by ROS, which cause strand breaks, cross-links, and chromosomal rearrangements. Apoptotic processes associated with ROS could also contribute to this result.
Further research will provide a more detailed description of the pathogenesis of sperm damage due to OMV.
Link to journal:
- Folliero, V., Santonastaso, M., Dell’Annunziata, F., et al. (2022). Effect of Escherichia coli outer membrane vesicles on sperm function. Pathogens. doi:10.3390/pathogens11070782.
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