Novel immunocontraceptive targets in mammals: uterine secretions and the conceptus; a marsupial approach.
We report the first immunocontraceptive trial in mammals using a uterine-secreted protein, the marsupial shell coat protein 4 (CP4). The marsupial shell coat, which surrounds the conceptus for 60-80% of gestation, is secreted by the uterine epithelium. Following immunization against glutathione S-transferase (GST)-CP4, the fertility of female common brushtail possums (n=6) was significantly reduced (P=0.000), and this reduction in fertility was positively correlated with the maximum GST-CP4 humoral immune response (P=0.025). Ultrastructural examination of the reproductive tract indicated that the cell-mediated immune response against GST-CP4 targeted the shell coat, the shell-free conceptus and the uterine glandular epithelium, thus preventing normal conceptus development and uterine secretion of shell coat proteins and nutrients. These results show that uterine-secreted proteins are promising immunocontraceptive targets, especially in pest mammal species, e.g. possum, rabbit and horse, that have uterine-secreted additions to embryonic coats, or that have late implantation requiring uterine nutrient provisioning from secretions.
Menkhorst
E M
EM
Department of Zoology, The University of Melbourne, Parkville, Victoria 3010, Australia.
Cui
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S
Selwood
L
L
D000818:Animals; D000917:Antibody Formation; D001324:Autoantigens / Q000494:pharmacology; D001755:Blastocyst / Q000187:drug effects / Q000502:physiology*; D003269:Contraception, Immunologic / Q000662:veterinary*; D004848:Epithelium / Q000276:immunology; D030762:Estrous Cycle; D005260:Female; D007114:Immunization; D007150:Immunohistochemistry; D008322:Mammals / Q000276:immunology*; D008394:Marsupialia / Q000276:immunology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011506:Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D014599:Uterus / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
D001324:Autoantigens; D011506:Proteins