IMMUNIZATION WITH SYNTHETIC PEPTIDE SEGMENTS OF A SPERM PROTEIN IMPAIR FERTILITY IN RATS

The nucleotide sequence of the cDNA encoding a sperm protein (rSMP-B) was determined in a previous study. Two peptide segments corresponding to the extracellular domain of the deduced sperm polypeptide were syn thesized as multiple antigen peptide (MAP) and designated as rSMP-229 and rSMP-230. Polyclonal antibodies were raised against the two MAPs. Sera obtained from rabbits immunized with rSMP-230 interacted with hum an and rabbit sperm membrane proteins with estimated molecular sizes o f 72 and 20.1 kD, respectively. Adult female and male rats were immuni zed with the MAPs and their fertilities determined. Immunization of fe male rats with rSMP-229 and rSMP-230 induced infertility in 25% and 83 % of the treated animals, respectively. All male rats immunized with r SMP-229 remained fertile; whereas animals immunized with rSMP-230 did not mate with normal cycling female rats. Three impotent male rats wer e found to regain their mating potency 45 days after the last booster injection. These findings demonstrated that immunization with rSMP-230 induced a reversible impotency in male rats. Serum testosterone and L H levels were reduced in rSMP-230-immunized male rats and were elevate d in rSMP-229-immunized animals. Histopatho-logical examination of sec tions of testes from male rats immunized with rSMP-230 showed impairme nt of spermatogenesis and sloughing of germ cells into the lumen of th e seminiferous tubules. The testes of male rats immunized with rSMP-22 9 showed normal morphology and active spermatogenesis with scattered f oci of nodular hyperplasia of Leydig cells in the interstitial areas. In conclusion, immunization with synthetic peptide segments correspond ing to different domains of a deduced sperm protein induced infertilit y in a significant number of female rats and transient impotency in ma le rats.