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

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.