Immunocontraceptive properties of recombinant sperm protein DE: implications for the development of novel contraceptives.
OBJECTIVE
To evaluate the immunocontraceptive properties of recombinant DE, a sperm epididymal protein involved in fertilization, via an experimental study in rats as a critical step toward the development of a human immunocontraceptive.


METHODS
In vivo study in rats.


METHODS
Animal care facility of an academic research center.


METHODS
Seventy-four 90-day-old Wistar male and female rats distributed into three groups.


METHODS
Animals received five injections (intramuscular and subcutaneous) of recombinant DE (recDE), native DE (nDE), or MBP (maltose-binding protein). At various times, animals were anesthetized and bled.


METHODS
Anti-DE levels and tissue specificity of sera were evaluated by enzyme-linked immunosorbent assay (ELISA) and Western blot, respectively. Fertility was analyzed by natural mating. The testes and epididymides were analyzed by histology.


RESULTS
Recombinant DE raised an immune response with the same kinetics and higher anti-DE levels than that elicited by nDE. Sera against recDE recognized epitopes of DE that were different from those recognized by anti-nDE sera but specifically reacted with DE in epididymis and sperm without cross-reacting with other tissues tested. Male and female recDE-injected animals presented a statistically significant reduction in their fertility with no evidence of pathologic effects.


CONCLUSIONS
Recombinant DE is able to both elicit a specific immune response and inhibit male and female fertility, supporting the use of this sperm epididymal protein for the development of an immunocontraceptive approach.
Ellerman
Diego A
DA
Instituto de Biología y Medicina Experimental (IBYME-CONICET), Vuelta de Obligado 2490, Buenos Aires (1428), Argentina.
Busso
Dolores
D
Maldera
Julieta A
JA
Cuasnicú
Patricia S
PS
D000818:Animals; D000906:Antibodies / Q000097:blood; D000917:Antibody Formation / Q000187:drug effects*; D000918:Antibody Specificity; D003269:Contraception, Immunologic; D003270:Contraceptive Agents / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D030501:Epididymal Secretory Proteins / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D005298:Fertility / Q000187:drug effects* / Q000276:immunology; D007114:Immunization; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology
D000906:Antibodies; D003270:Contraceptive Agents; C486320:Crisp3 protein, rat; D030501:Epididymal Secretory Proteins; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins