Abstract
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.
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- Beck K., Hunter I., Engel J. Structure and function of laminin: anatomy of a multidomain glycoprotein. FASEB J. 1990 Feb 1;4(2):148–160. doi: 10.1096/fasebj.4.2.2404817. [DOI] [PubMed] [Google Scholar]
- Bronson R. A., Fusi F. Evidence that an Arg-Gly-Asp adhesion sequence plays a role in mammalian fertilization. Biol Reprod. 1990 Dec;43(6):1019–1025. doi: 10.1095/biolreprod43.6.1019. [DOI] [PubMed] [Google Scholar]
- Carey S. W., Klein N. W. Autoantibodies to laminin and other basement membrane proteins in sera from monkeys with histories of reproductive failure identified by cultures of whole rat embryos. Fertil Steril. 1989 Apr;51(4):711–718. doi: 10.1016/s0015-0282(16)60626-x. [DOI] [PubMed] [Google Scholar]
- Chambers B. J., Klein N. W. Role of laminin autoantibodies on the embryo toxicity of sera from mercuric chloride treated brown Norway rats. Reprod Toxicol. 1993 Jul-Aug;7(4):333–341. doi: 10.1016/0890-6238(93)90022-y. [DOI] [PubMed] [Google Scholar]
- Coelho C. N., Weber J. A., Klein N. W., Daniels W. G., Hoagland T. A. Whole rat embryos require methionine for neural tube closure when cultured on cow serum. J Nutr. 1989 Nov;119(11):1716–1725. doi: 10.1093/jn/119.11.1716. [DOI] [PubMed] [Google Scholar]
- Cowchock S. Autoantibodies and pregnancy wastage. Am J Reprod Immunol. 1991 Aug;26(1):38–41. doi: 10.1111/j.1600-0897.1991.tb00700.x. [DOI] [PubMed] [Google Scholar]
- Dietrich G., Kaveri S. V., Kazatchkine M. D. Modulation of autoimmunity by intravenous immune globulin through interaction with the function of the immune/idiotypic network. Clin Immunol Immunopathol. 1992 Jan;62(1 Pt 2):S73–S81. doi: 10.1016/0090-1229(92)90044-o. [DOI] [PubMed] [Google Scholar]
- Ferrari D. A., Gilles P. A., Klein N. W., Nadler D., Weeks B. S., Lammi-Keefe C. J., Hillman R. E., Carey S. W., Ying Y. K., Maier D. Rat embryo development on human sera is related to numbers of previous spontaneous abortions and nutritional factors. Am J Obstet Gynecol. 1994 Jan;170(1 Pt 1):228–236. doi: 10.1016/s0002-9378(94)70412-0. [DOI] [PubMed] [Google Scholar]
- Foidart J. M., Yaar M., Figueroa A., Wilk A., Brown K. S., Liotta L. A. Abortion in mice induced by intravenous injections of antibodies to type IV collagen or laminin. Am J Pathol. 1983 Mar;110(3):346–357. [PMC free article] [PubMed] [Google Scholar]
- Hill J. A. Immunological contributions to recurrent pregnancy loss. Baillieres Clin Obstet Gynaecol. 1992 Sep;6(3):489–505. doi: 10.1016/s0950-3552(05)80007-0. [DOI] [PubMed] [Google Scholar]
- Hodgen G. D., Stouffer R. L., Barber D. L., Nixon W. E. Serum estradiol and progesterone during pregnancy and the status of the corpus luteum at delivery in cynomolgus monkeys (Macaca fascicularis). Steroids. 1977 Aug;30(2):295–301. doi: 10.1016/0039-128x(77)90090-3. [DOI] [PubMed] [Google Scholar]
- Infante-Rivard C., David M., Gauthier R., Rivard G. E. Lupus anticoagulants, anticardiolipin antibodies, and fetal loss. A case-control study. N Engl J Med. 1991 Oct 10;325(15):1063–1066. doi: 10.1056/NEJM199110103251503. [DOI] [PubMed] [Google Scholar]
- Klein N. W., Plenefisch J. D., Carey S. W., Fredrickson W. T., Sackett G. P., Burbacher T. M., Parker R. M. Serum from monkeys with histories of fetal wastage causes abnormalities in cultured rat embryos. Science. 1982 Jan 1;215(4528):66–69. doi: 10.1126/science.7053560. [DOI] [PubMed] [Google Scholar]
- Kwak J. Y., Gilman-Sachs A., Beaman K. D., Beer A. E. Autoantibodies in women with primary recurrent spontaneous abortion of unknown etiology. J Reprod Immunol. 1992 Jun;22(1):15–31. doi: 10.1016/0165-0378(92)90003-m. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Lawley T. J., Stingl G., Katz S. I. Fetal and maternal risk factors in herpes gestationis. Arch Dermatol. 1978 Apr;114(4):552–555. [PubMed] [Google Scholar]
- Mooseker M. S. Organization, chemistry, and assembly of the cytoskeletal apparatus of the intestinal brush border. Annu Rev Cell Biol. 1985;1:209–241. doi: 10.1146/annurev.cb.01.110185.001233. [DOI] [PubMed] [Google Scholar]
- Petri M., Allbritton J. Fetal outcome of lupus pregnancy: a retrospective case-control study of the Hopkins Lupus Cohort. J Rheumatol. 1993 Apr;20(4):650–656. [PubMed] [Google Scholar]
- Pullen G. R., Fitzgerald M. G., Hosking C. S. Antibody avidity determination by ELISA using thiocyanate elution. J Immunol Methods. 1986 Jan 22;86(1):83–87. doi: 10.1016/0022-1759(86)90268-1. [DOI] [PubMed] [Google Scholar]
- Rasmussen M. V., Klein N. W., Abrahamson D. R., Chung A. E. Effects of laminin monoclonal antibodies on the development of cultured rat embryos. Teratology. 1994 Jan;49(1):20–28. doi: 10.1002/tera.1420490105. [DOI] [PubMed] [Google Scholar]
- Sakamoto N., Iwahana M., Tanaka N. G., Osada Y. Inhibition of angiogenesis and tumor growth by a synthetic laminin peptide, CDPGYIGSR-NH2. Cancer Res. 1991 Feb 1;51(3):903–906. [PubMed] [Google Scholar]
- Tashiro K., Sephel G. C., Greatorex D., Sasaki M., Shirashi N., Martin G. R., Kleinman H. K., Yamada Y. The RGD containing site of the mouse laminin A chain is active for cell attachment, spreading, migration and neurite outgrowth. J Cell Physiol. 1991 Mar;146(3):451–459. doi: 10.1002/jcp.1041460316. [DOI] [PubMed] [Google Scholar]
- Tung P. S., Fritz I. B. Interactions of Sertoli cells with laminin are essential to maintain integrity of the cytoskeleton and barrier functions of cells in culture in the two-chambered assembly. J Cell Physiol. 1993 Jul;156(1):1–11. doi: 10.1002/jcp.1041560102. [DOI] [PubMed] [Google Scholar]
- Weeks B. S., Holloway E., Klotman P. E., Akiyama S. K., Schnaper H. W., Kleinman H. K. 12-O-tetradecanoylphorbol 13-acetate stimulates human T-lymphocyte adherence to the fibronectin RGD domain and the laminin IKVAV domain. Cell Immunol. 1994 Jan;153(1):94–104. doi: 10.1006/cimm.1994.1008. [DOI] [PubMed] [Google Scholar]
- Weeks B. S., Klein N. W. In vitro and in vivo embryo toxicity of antilaminin antibodies in the rat. Am J Reprod Immunol. 1989 Feb;19(2):57–64. doi: 10.1111/j.1600-0897.1989.tb00549.x. [DOI] [PubMed] [Google Scholar]
- Weeks B. S., Klein N. W., Kleinman H., Frederickson T., Sackett G. P. Laminin immunized monkeys develop sera toxic to cultured rat embryos and fail to reproduce. Teratology. 1989 Jul;40(1):47–57. doi: 10.1002/tera.1420400107. [DOI] [PubMed] [Google Scholar]
- Weiner H. L., Mackin G. A., Matsui M., Orav E. J., Khoury S. J., Dawson D. M., Hafler D. A. Double-blind pilot trial of oral tolerization with myelin antigens in multiple sclerosis. Science. 1993 Feb 26;259(5099):1321–1324. doi: 10.1126/science.7680493. [DOI] [PubMed] [Google Scholar]
- Yamada H., Polgar K., Hill J. A. Cell-mediated immunity to trophoblast antigens in women with recurrent spontaneous abortion. Am J Obstet Gynecol. 1994 May;170(5 Pt 1):1339–1344. doi: 10.1016/s0002-9378(94)70153-9. [DOI] [PubMed] [Google Scholar]