An experimental study to decipher the implications of antigenic sharing between Proteus mirabilis and mouse spermatozoa in eliciting an antisperm immune response: A potential culprit in immune infertility

The present study aims to investigate the antigenic cross reactivity between the receptor from Proteus mirabilis and spermatozoa against a common sperm immobilization factor, SIF, by calorimetric and competitive inhibition studies, and the immunogenicity of this receptor to evoke the formation of antisperm antibodies and their subsequent role in fertility outcome. The sperm binding receptor from Proteus mirabilis (PM-SBR) was extracted from ultrasonicated cell debris by treating it for 12 h at 37°C with 1 M NaCl. After being purified by gel permeation chromatography, its molecular weight as determined by SDS-PAGE was observed to be ≈ 47 kDa. The detrimental impacts of Sperm immobilizing factor (SIF) on spermatozoa viz. motility, viability, and morphology were mitigated when SIF was preincubated with various concentrations of PM-SBR. Using isothermal titration calorimetry, the entropy of the SIF-PM-SBR interaction was found to be -18.31 kJ/mol, whereas the free energy was 28.4 J/mol K. FTIR analysis was used to evaluate the binding interactions between PM-SBR and SIF. In addition, mice that were administered antibodies against PM-SBR were unable to conceive, in contrast to mice that were administered Phosphate buffer saline (PBS) or pre-immunization serum as controls. In light of this, we may conclude that anti-PM-SBR antibodies act as anti-sperm antibodies. Our work found that molecular mimicry between Proteus mirabilis and spermatozoa may cause antisperm immune reactivity. As a result of an immunological response to PM-SBR, infected individuals may produce antibodies against an epitope similar to one found on spermatozoa which helps in developing new strategies for managing autoimmune responses and infertility.