Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1994 Dec;98(3):513–519. doi: 10.1111/j.1365-2249.1994.tb05521.x

MHC-associated immunopotentiation affects the embryo response to teratogens.

A Torchinsky 1, A Fein 1, H J Carp 1, V Toder 1
PMCID: PMC1534510  PMID: 7994915

Abstract

The present study was performed to evaluate whether the effect of environmental teratogens can be modified by maternal immunostimulation. Two chemicals, cyclophosphamide (CP) and 2,3-quinoxalinedimetanol,1,4-dioxide (QD) were used as the reference teratogens (RT). The response to these RT was investigated in two animal models: (i) primigravid C57Bl/6 mice who underwent intrauterine immunization with allogeneic paternal (CBA/J), third-party (BALB/c) or syngeneic male splenocytes 21 days before mating; (ii) C57Bl/6 and CBA/J mice who were treated with RT during the second pregnancy only, after a different mating combination (syngeneic or allogeneic) in the first and the second pregnancy. Different doses of CP and QD were injected on days 12 and 9 of pregnancy, respectively. On day 19 of pregnancy implantation sites, resorptions, live and dead fetuses were recorded and live fetuses were examined for external and internal malformations with methods routinely used in teratological study. It was shown that intrauterine immunopotentiation with allogeneic paternal splenocytes clearly enhances the tolerance of F1 embryos to RT. Thus, in CP-treated females the resorption rate and the proportion of malformed fetuses were significantly reduced. It was followed by an almost two-fold increase in fetal weight. The protective effect of such immunization in QD-treated females was manifested as a dramatic decrease of the proportion of malformed fetuses and the resorption rate. Syngeneic splenocytes could not significantly influence an embryo's sensitivity to RT. The response to RT was also significantly weaker in the second pregnancy of female mice mated twice allogeneically than that observed in allogeneically mated primigravid mice. These results show that the embryo's response to environmental teratogens may be influenced by fetomaternal immune interactions.

Full text

PDF
513

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson D. J., Bach D. L., Yunis E. J., DeWolf W. C. Major histocompatibility antigens are not expressed on human epididymal sperm. J Immunol. 1982 Aug;129(2):452–454. [PubMed] [Google Scholar]
  2. Athanassakis I., Bleackley R. C., Paetkau V., Guilbert L., Barr P. J., Wegmann T. G. The immunostimulatory effect of T cells and T cell lymphokines on murine fetally derived placental cells. J Immunol. 1987 Jan 1;138(1):37–44. [PubMed] [Google Scholar]
  3. Beer A. E., Quebbeman J. F., Ayers J. W., Haines R. F. Major histocompatibility complex antigens, maternal and paternal immune responses, and chronic habitual abortions in humans. Am J Obstet Gynecol. 1981 Dec 15;141(8):987–999. doi: 10.1016/s0002-9378(16)32690-4. [DOI] [PubMed] [Google Scholar]
  4. Bertini R., Coccia P., Pagani P., Marinello C., Salmona M., D'Incalci M. Interferon inducers increase O6-alkylguanine-DNA alkyltransferase in the rat liver. Carcinogenesis. 1990 Jan;11(1):181–183. doi: 10.1093/carcin/11.1.181. [DOI] [PubMed] [Google Scholar]
  5. Biddle F. G. Use of dose-response relationships to discriminate between the mechanisms of cleft-palate induction by different teratogens: an argument for discussion. Teratology. 1978 Oct;18(2):247–252. doi: 10.1002/tera.1420180210. [DOI] [PubMed] [Google Scholar]
  6. Bonner J. J. The H-2 genetic complex, dexamethasone-induced cleft palate, and other craniofacial anomalies. Curr Top Dev Biol. 1984;19:193–215. doi: 10.1016/s0070-2153(08)60400-7. [DOI] [PubMed] [Google Scholar]
  7. Brent R. L., Beckman D. A., Jensen M., Koszalka T. R. Experimental yolk sac dysfunction as a model for studying nutritional disturbances in the embryo during early organogenesis. Teratology. 1990 Apr;41(4):405–413. doi: 10.1002/tera.1420410406. [DOI] [PubMed] [Google Scholar]
  8. Chaouat G., Kolb J. P., Kiger N., Stanislawski M., Wegmann T. G. Immunologic consequences of vaccination against abortion in mice. J Immunol. 1985 Mar;134(3):1594–1598. [PubMed] [Google Scholar]
  9. Chávez D. J., McIntyre J. A. Sera from women with histories of repeated pregnancy losses cause abnormalities in mouse peri-implantation blastocysts. J Reprod Immunol. 1984 Aug;6(5):273–281. doi: 10.1016/0165-0378(84)90027-5. [DOI] [PubMed] [Google Scholar]
  10. Cohen J. J., Duke R. C., Fadok V. A., Sellins K. S. Apoptosis and programmed cell death in immunity. Annu Rev Immunol. 1992;10:267–293. doi: 10.1146/annurev.iy.10.040192.001411. [DOI] [PubMed] [Google Scholar]
  11. Coulam C. B., Coulam C. H. Update on immunotherapy for recurrent pregnancy loss. Am J Reprod Immunol. 1992 Apr-May;27(3-4):124–127. doi: 10.1111/j.1600-0897.1992.tb00738.x. [DOI] [PubMed] [Google Scholar]
  12. Ferrari L., Kremers P., Batt A. M., Gielen J. E., Siest G. Differential effects of human recombinant interleukin-1 beta on cytochrome P-450-dependent activities in cultured fetal rat hepatocytes. Drug Metab Dispos. 1992 May-Jun;20(3):407–412. [PubMed] [Google Scholar]
  13. Gibson J. E., Becker B. A. The teratogenicity of cyclophosphamide in mice. Cancer Res. 1968 Mar;28(3):475–480. [PubMed] [Google Scholar]
  14. Goldman A. S. Biochemical mechanism of glucocorticoid-and phenytoin-induced cleft palate. Curr Top Dev Biol. 1984;19:217–239. doi: 10.1016/s0070-2153(08)60401-9. [DOI] [PubMed] [Google Scholar]
  15. Hunt J. S. Current topic: the role of macrophages in the uterine response to pregnancy. Placenta. 1990 Nov-Dec;11(6):467–475. doi: 10.1016/s0143-4004(05)80192-4. [DOI] [PubMed] [Google Scholar]
  16. Hunt J. S., Manning L. S., Mitchell D., Selanders J. R., Wood G. W. Localization and characterization of macrophages in murine uterus. J Leukoc Biol. 1985 Aug;38(2):255–265. doi: 10.1002/jlb.38.2.255. [DOI] [PubMed] [Google Scholar]
  17. Jensen M., Lloyd J. B., Koszalka T. R., Beckman D. A., Brent R. L. Preparation and developmental toxicity of monoclonal antibodies against rat visceral yolk sac antigens. Teratology. 1989 Nov;40(5):505–511. doi: 10.1002/tera.1420400513. [DOI] [PubMed] [Google Scholar]
  18. Lemoli R. M., Strife A., Clarkson B. D., Haley J. D., Gulati S. C. TGF-beta 3 protects normal human hematopoietic progenitor cells treated with 4-hydroperoxycyclophosphamide in vitro. Exp Hematol. 1992 Dec;20(11):1252–1256. [PubMed] [Google Scholar]
  19. Matrisian L. M., Ganser G. L., Kerr L. D., Pelton R. W., Wood L. D. Negative regulation of gene expression by TGF-beta. Mol Reprod Dev. 1992 Jun;32(2):111–120. doi: 10.1002/mrd.1080320206. [DOI] [PubMed] [Google Scholar]
  20. Moore M. A., Warren D. J. Synergy of interleukin 1 and granulocyte colony-stimulating factor: in vivo stimulation of stem-cell recovery and hematopoietic regeneration following 5-fluorouracil treatment of mice. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7134–7138. doi: 10.1073/pnas.84.20.7134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Moreb J., Zucali J. R., Rueth S. The effects of tumor necrosis factor-alpha on early human hematopoietic progenitor cells treated with 4-hydroperoxycyclophosphamide. Blood. 1990 Aug 15;76(4):681–689. [PubMed] [Google Scholar]
  22. Neta R., Oppenheim J. J., Douches S. D. Interdependence of the radioprotective effects of human recombinant interleukin 1 alpha, tumor necrosis factor alpha, granulocyte colony-stimulating factor, and murine recombinant granulocyte-macrophage colony-stimulating factor. J Immunol. 1988 Jan 1;140(1):108–111. [PubMed] [Google Scholar]
  23. Poüs C., Giroud J. P., Damais C., Raichvarg D., Chauvelot-Moachon L. Effect of recombinant human interleukin-1 beta and tumor necrosis factor alpha on liver cytochrome P-450 and serum alpha-1-acid glycoprotein concentrations in the rat. Drug Metab Dispos. 1990 Jul-Aug;18(4):467–470. [PubMed] [Google Scholar]
  24. Rotello R. J., Lieberman R. C., Purchio A. F., Gerschenson L. E. Coordinated regulation of apoptosis and cell proliferation by transforming growth factor beta 1 in cultured uterine epithelial cells. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3412–3415. doi: 10.1073/pnas.88.8.3412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Thiery J. P., Boyer B. The junction between cytokines and cell adhesion. Curr Opin Cell Biol. 1992 Oct;4(5):782–792. doi: 10.1016/0955-0674(92)90101-h. [DOI] [PubMed] [Google Scholar]
  26. Wegmann T. G. Placental immunotrophism: maternal T cells enhance placental growth and function. Am J Reprod Immunol Microbiol. 1987 Oct;15(2):67–69. doi: 10.1111/j.1600-0897.1987.tb00156.x. [DOI] [PubMed] [Google Scholar]
  27. Zigril M., Fein A., Carp H., Toder V. Immunopotentiation reverses the embryotoxic effect of serum from women with pregnancy loss. Fertil Steril. 1991 Oct;56(4):653–659. doi: 10.1016/s0015-0282(16)54595-6. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES