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. 1977 Dec;30(3):393–402.

A study of maternal lymphoid organs and the progeny following treatment with immunomodulating agents during pregnancy.

J R Scott, T L Feldbush, J M Covault
PMCID: PMC1541141  PMID: 342160

Abstract

Whether differences in foetoplacental weight and post-implantation mortality in rodents are secondary to heterosis and inbreeding depression or antigenic differences between mother and foetus has been a continuing controversy. To determine whether non-specific depression or stimulation of the maternal immune system affects the success of the foetoplacental allograft, groups of virgin Fischer (Ag-B1) females of similar age and weight mated with DA (Ag-B4) males were treated with daily intraperitoneal injections of: (a) saline, (b) methylprednisolone (MP), 1-0 mg/kg, (c) cyclophosphamide (CY), 3.0 mg/kg, or (d) azathioprine (AZ), 3.0 mg/kg; or they were injected intraperitoneally on the fifth day of gestation with: (a) B. pertussis, 1.0 ml, (b) C. parvum, 0.2 ml, or (c) BCG, 0.1 ml. None of the immunostimulating agents were detrimental to the progeny, but the immunosupprissive drugs caused an increased percentage of foetal deaths and foetoplacental growth retardation. The reduced foetal and placental size induced by CY or AZ could be partially blocked by simultaneous maternal treatment with BCG. Analysis of mean maternal weight gain, spleen weight assays, changes in the lymph nodes draining the uterus and comparison of data from non-pregnant animals and syngeneic pregnancies treated with these agents suggest that immunosuppressive drugs reduce foetal survival rates and produce foetoplacental growth retardation via a combination of immunological and cytotoxic mechanisms.

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Selected References

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

  1. Aisenberg A. C., Murray C. Cell transfer studies in cyclophosphamide-induced tolerance. Cell Immunol. 1973 Apr;7(1):143–151. doi: 10.1016/0008-8749(73)90190-1. [DOI] [PubMed] [Google Scholar]
  2. BILLINGTON W. D. INFLUENCE OF IMMUNOLOGICAL DISSIMILARITY OF MOTHER AND FOETUS ON SIZE OF PLACENTA IN MICE. Nature. 1964 Apr 18;202:317–318. doi: 10.1038/202317a0. [DOI] [PubMed] [Google Scholar]
  3. Bach J. F. The pharmacological and immunological basis for the use of immunosuppressive drugs. Drugs. 1976;11(1):1–13. doi: 10.2165/00003495-197611010-00001. [DOI] [PubMed] [Google Scholar]
  4. Baldwin R. W., Pimm M. V. BCG immunotherapy of pulmonary growths from intravenously transferred rat tumour cells. Br J Cancer. 1973 Jan;27(1):48–54. doi: 10.1038/bjc.1973.6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Beer A. E., Billingham R. E., Scott J. R. Immunogenetic aspects of implantation, placentation and feto-placental growth rates. Biol Reprod. 1975 Feb;12(1):176–189. doi: 10.1095/biolreprod12.1.176. [DOI] [PubMed] [Google Scholar]
  6. Beer A. E., Scott J. R., Billingham R. E. Histoincompatibility and maternal immunological status as determinants of fetoplacental weight and litter size in rodents. J Exp Med. 1975 Jul 1;142(1):180–196. doi: 10.1084/jem.142.1.180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bonney W. W., Feldbush T. L., Neufeld S. E. Effectiveness and toxicity of immunosuppressive agents: inhibition of the rat popliteal node graft-vs.-host reaction. J Pharmacol Exp Ther. 1974 Sep;190(3):576–584. [PubMed] [Google Scholar]
  8. Botta J. A., Jr, Hawkins H. C., Weikel J. H., Jr Effects of cyclophosphamide on fertility and general reproductive performance of rats. Toxicol Appl Pharmacol. 1974 Mar;27(3):602–611. doi: 10.1016/0041-008x(74)90039-8. [DOI] [PubMed] [Google Scholar]
  9. Chaube S., Swinyard C. A. Cellular and biochemical aspects of growth retardation in rat fetuses induced by maternal administration of selected anticancer agents. Teratology. 1975 Dec;12(3):259–270. doi: 10.1002/tera.1420120307. [DOI] [PubMed] [Google Scholar]
  10. Clarke A. G. The effects of maternal pre-immunization on pregnancy in the mouse. J Reprod Fertil. 1971 Mar;24(3):369–375. doi: 10.1530/jrf.0.0240369. [DOI] [PubMed] [Google Scholar]
  11. Cottier H., Turk J., Sobin L. A proposal for a standardized system of reporting human lymph node morphology in relation to immunological function. Bull World Health Organ. 1972;47(3):375–417. [PMC free article] [PubMed] [Google Scholar]
  12. Coté C. J., Meuwissen H. J., Pickering R. J. Effects on the neonate of prednisone and azathioprine administered to the mother during pregnancy. J Pediatr. 1974 Sep;85(3):324–328. doi: 10.1016/s0022-3476(74)80109-5. [DOI] [PubMed] [Google Scholar]
  13. Farquhar D., Loo T. L., Gutterman J. U., Hersh E. M., Luna M. A. Inhibition of drug-metabolizing enzymes in the rat after Bacillus Calmette-Guérin treatment. Biochem Pharmacol. 1976 Jul 1;25(13):1529–1535. doi: 10.1016/0006-2952(76)90072-1. [DOI] [PubMed] [Google Scholar]
  14. Fisher B., Wolmark N., Rubin H. Further observations on the inhibition of tumor growth by Corynebacterium parvum with cyclophosphamide. III. Effect of C. parvum on cyclophosphamide metabolism. J Natl Cancer Inst. 1976 Jul;57(1):225–226. doi: 10.1093/jnci/57.1.225. [DOI] [PubMed] [Google Scholar]
  15. Fournier C., Bach M. A., Dardenne M., Bach J. F. Selective action of azathioprine on T cells. Transplant Proc. 1973 Mar;5(1):523–526. [PubMed] [Google Scholar]
  16. Gelfand M. C., Steinberg A. D. Therapeutic studies in NZB-W mice. II. Relative efficacy of azathioprine, cyclophosphamide and methylprednisolone. Arthritis Rheum. 1972 May-Jun;15(3):247–252. doi: 10.1002/art.1780150305. [DOI] [PubMed] [Google Scholar]
  17. Hetherington C. M. The absence of any effect of maternal-fetal incompatibility at the H-2 and H-3 loci on pregnancy in the mouse. J Reprod Fertil. 1973 Apr;33(1):135–139. doi: 10.1530/jrf.0.0330135. [DOI] [PubMed] [Google Scholar]
  18. James D. A. Some effects of immunological factors on gestation in mice. J Reprod Fertil. 1967 Oct;14(2):265–275. doi: 10.1530/jrf.0.0140265. [DOI] [PubMed] [Google Scholar]
  19. Maroni E. S., de Sousa M. A. The lymphoid organs during pregnancy in the mouse. A comparison between a syngeneic and an allogeneic mating. Clin Exp Immunol. 1973 Jan;13(1):107–124. [PMC free article] [PubMed] [Google Scholar]
  20. McLean J. M., Mosley J. G., Gibbs A. C. Changes in the thymus, spleen and lymph nodes during pregnancy and lactation in the rat. J Anat. 1974 Nov;118(Pt 2):223–229. [PMC free article] [PubMed] [Google Scholar]
  21. Paterson P. Y., Drobish D. G. Cyclophosphamide: effect on experimental allergic encephalomyelitis in Lewis rats. Science. 1969 Jul 11;165(3889):191–192. doi: 10.1126/science.165.3889.191. [DOI] [PubMed] [Google Scholar]
  22. Rosenkrantz J. G., Githens J. H., Cox S. M., Kellum D. L. Azathioprine (Imuran) and pregnancy. Am J Obstet Gynecol. 1967 Feb 1;97(3):387–394. doi: 10.1016/0002-9378(67)90503-0. [DOI] [PubMed] [Google Scholar]
  23. SCOTHORNE R. J., MCGREGOR I. A. Cellular changes in lymph nodes and spleen following skin homografting in the rabbit. J Anat. 1955 Jul;89(3):283–292. [PMC free article] [PubMed] [Google Scholar]
  24. SIMONSEN M. Graft versus host reactions. Their natural history, and applicability as tools of research. Prog Allergy. 1962;6:349–467. [PubMed] [Google Scholar]
  25. Saarikoski S., Seppälä M. Immunosuppression during pregnancy: transmission of azathioprine and its metabolites from the mother to the fetus. Am J Obstet Gynecol. 1973 Apr 15;115(8):1100–1106. doi: 10.1016/0002-9378(73)90559-0. [DOI] [PubMed] [Google Scholar]
  26. Sadler T. E., Castro J. E. Lack of immunological and anti-tumour effects of orally administered Corynebacterium papvum in mice. Br J Cancer. 1975 Mar;31(3):359–363. doi: 10.1038/bjc.1975.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Singh S., Sanyal A. K. Skeletal malformations of forelimbs of rat fetuses caused by maternal administration of cyclophosphamide during pregnancy. J Anat. 1974 Feb;117(Pt 1):179–189. [PMC free article] [PubMed] [Google Scholar]
  28. Smart J. L., Adlard B. P., Dobbing J. Effect of maternal undernutrition and other factors on birth weight in the rat. Biol Neonate. 1972;20(3):236–244. doi: 10.1159/000240467. [DOI] [PubMed] [Google Scholar]
  29. Stirrat G. M. Prescribing problems in the second half of pregnancy and during lactation. Obstet Gynecol Surv. 1976 Jan;31(1):1–7. doi: 10.1097/00006254-197601000-00001. [DOI] [PubMed] [Google Scholar]
  30. Sweeney W. T., Seibel H. R. Histamine release from peritoneal mast cells of tumor susceptible rats following periods of tumor growth and sensitization with tumor antigens and B. pertussis. Int Arch Allergy Appl Immunol. 1973;45(5):789–794. doi: 10.1159/000231078. [DOI] [PubMed] [Google Scholar]
  31. Sörén L. Immunological reactivity of lymphocytes in multiparous females after strain specific matings. Nature. 1967 Feb 11;213(5076):621–622. doi: 10.1038/213621a0. [DOI] [PubMed] [Google Scholar]
  32. Tilney N. L. Patterns of lymphatic drainage in the adult laboratory rat. J Anat. 1971 Sep;109(Pt 3):369–383. [PMC free article] [PubMed] [Google Scholar]
  33. Tinbergen W. J. The effects of some immunosuppressive agents on kidney graft survival in rats. Transplantation. 1968 Mar;6(2):203–207. doi: 10.1097/00007890-196803000-00006. [DOI] [PubMed] [Google Scholar]
  34. Tsakraklides V., Anastassiades O. T., Kersey J. H. Prognostic significance of regional lymph node histology in uterine cervical cancer. Cancer. 1973 Apr;31(4):860–868. doi: 10.1002/1097-0142(197304)31:4<860::aid-cncr2820310415>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]

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