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Keywords:

  • Antibodies;
  • antisperm antibodies;
  • fertility;
  • immunoinfertility;
  • spermatozoa

Problem

A human sperm antigen of molecular size of about 80kDa (80kDa HSA) has been reported to be sperm-specific, conserved and responsible for inducing immunological infertility. The partial N-terminal amino acid sequence of 80kDa HSA (peptide NT) and its peptides obtained by enzymatic digestion with endoproteinase Lys-C (peptides 1–4) and with endoproteinase Glu-C (peptides 5 and 6) did not show sequence homology with any of the proteins of the GenBank. The peptides NT, 1, 2, 3 and 4 were synthesized, conjugated to keyhole limpet hemocyanin and used as an immunogen to raise the antibodies in rabbits. Peptide 3 did not elicit significant antibody titer while peptides NT, 1, 2 and 4 elicited significant antibody titer and immunobiologically mimicked the native protein.

Method of study

Effects of passive administration of two injections each of 200 μL of antibodies or 10 and 40 μg purified immunoglobulins to 80kDa HSA, peptides NT, 1, 2 and 4 on fertility in male and female rats were investigated.

Results

Passive administration of antibodies to 80kDa HSA and its peptides NT, 1, 2 and 4 resulted in agglutination of epididymal spermatozoa with loss of motility but had no effect on sperm count or weights of the reproductive organs. These animals failed to impregnate normal female rats. Passive administration of these antibodies to female rats also resulted in infertility. The presence of antibodies was detected by enzyme-linked immunosorbent assay in uterine secretions of animals treated with antipeptide antibody. The presence of agglutinated spermatozoa was observed in the post-coital vaginal smears of these animals. The immunized females were found to be ovulating normally and the number of corpora lutea were unaltered. Of the four antipeptide antibodies studied, antibodies to peptides NT and 1 were most effective in inhibiting fertility both in male as well as female rats. Hence, the antifertility studies were further confirmed by passive administration of 10 and 40 μg of purified immunoglobulins of antibodies to NT and 1, which resulted in a dose-dependent inhibition of fertility in male and female rats.

Conclusions

The study demonstrated that the synthetic peptides of 80kDa HSA immunobiologically mimicked the native protein and impaired fertility following passive administration of antipeptide antibodies and hence, suggested the suitability of synthetic peptides of 80kDa HSA as candidates for development of antifertility vaccine.