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 synthesized 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 human and rabbit sperm membrane proteins with estimated molecular sizes of 72 and 20.1 kD, respectively. Adult female and male rats were immunized with the MAPs and their fertilities determined. Immunization of female rats with rSMP-229 and rSMP-230 induced infertility in 25% and 83% of the treated animals, respectively. All male rats immunized with rSMP-229 remained fertile; whereas animals immunized with rSMP-230 did not mate with normal cycling female rats. Three impotent male rats were 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 LH levels were reduced in rSMP-230-immunized male rats and were elevated in rSMP-229-immunized animals. Histopathological examination of sections of testes from male rats immunized with rSMP-230 showed impairment of spermatogenesis and sloughing of germ cells into the lumen of the seminiferous tubules. The testes of male rats immunized with rSMP-229 showed normal morphology and active spermatogenesis with scattered foci of nodular hyperplasia of Leydig cells in the interstitial areas. In conclusion, immunization with synthetic peptide segments corresponding to different domains of a deduced sperm protein induced infertility in a significant number of female rats and transient impotency in male rats.
Vanage
G R
GR
Center for Biomedical Research, Population Council, New York, NY 10021.
Jaiswal
Y K
YK
Lu
Y A
YA
Tam
J P
JP
Wang
L F
LF
Koide
S S
SS
D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007106:Immune Sera; D007114:Immunization; D015151:Immunoblotting; D007246:Infertility / Q000276:immunology*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013094:Spermatozoa / Q000276:immunology*; D013737:Testis / Q000276:immunology / Q000473:pathology; D013739:Testosterone / Q000097:blood
D000954:Antigens, Surface; D007106:Immune Sera; D008565:Membrane Proteins; D010446:Peptide Fragments; C088507:rSMP (29-53); C088508:rSMP B (1-28); C049242:rSMP-B protein, human; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone