Reproduction and sera embryotoxicity after immunization of monkeys with the laminin peptides YIGSR, RGD, and IKVAV.
Monkeys with excellent reproductive histories were immunized with the laminin peptides YIGSR, RGD, IKVAV, and YD, a control sequence with no known biological function. Sera from the YIGSR-immunized monkey became toxic, causing neural tube defects in whole rat embryo cultures, and this monkey experienced fetal loss after immunization. Sera from the RGD-immunized monkey also became embryotoxic in culture after immunization, but this monkey appeared to become infertile as she failed to initiate a pregnancy for at least 2 years after immunization. In contrast, embryos cultured on sera from the IKVAV- or YD-immunized monkeys were predominantly normal and both monkeys completed successful pregnancies. Antibody levels to the respective peptides or to laminin were not predictive of embryotoxicity, but antibody binding to homogenized yolk sacs as well as to yolk sacs of cultured embryos was associated with sera embryotoxicity and reproductive outcomes in vivo. These observations suggested that the laminin sequences YIGSR and RGD may play a role in immune-mediated reproductive failure by reacting directly with embryonic tissue and could provide a basis for identifying individuals at risk for both spontaneous abortion and infertility.
Chambers
B J
BJ
Center for Environmental Health, University of Connecticut, Storrs 06269, USA.
Klein
N W
NW
Conrad
S H
SH
Ruppenthal
G C
GC
Sackett
G P
GP
Weeks
B S
BS
Kleinman
H K
HK
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000633:toxicity*; D001681:Biological Assay; D004622:Embryo, Mammalian / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007246:Infertility / Q000276:immunology*; D007797:Laminin / Q000276:immunology*; D008254:Macaca nemestrina; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology*; D051381:Rats; D013329:Structure-Activity Relationship
D000906:Antibodies; D007797:Laminin; D009842:Oligopeptides; D010446:Peptide Fragments; C081571:tyrosyl-isoleucyl-glycyl-seryl-arginine; C083321:isoleucyl-lysyl-valyl-alanyl-valine; C047981:arginyl-glycyl-aspartic acid