Immune function of young adult mice following in utero exposure to cyclophosphamide

Long-lasting organic damage has been reported following in utero exposure to certain environmental or therapeutic agents. The sensitivity of the developing immune system to chemical insult during organogenesis or histogenesis was evaluated in mice employing the known immunosuppressive agent cyclophosphamide (CY). Experiments were conducted employing one of the following treatment regimens: (1) 1 microgram/g X d intravenously on d 9-12 or 14-17 of gestation; (2) 5 micrograms/g intravenously on 12 of gestation; (3) 1, 2.5, or 5 micrograms/g X d intraperitoneally on d 12 of gestation; or (4) 5, 10, or 20 micrograms/g intraperitoneally on d 17 of gestation. There were no surviving pups born to mothers administered CY by schedule 2; otherwise, numbers of surviving offspring were not affected by drug treatment, and no gross terata were observed. Employing this variety of exposure protocols, consistent enhancement or suppression of cell-mediated or humoral immune function was not observed in offspring of treated dams. Reduced body weight in 5- and 8-wk-old progeny was noted after exposure to 20 micrograms/g on gestational d 17. Increased in vitro B-lymphocyte blastogenic response to lipopolysaccharide occurred in 5-wk-old animals, and production of antibody to sheep erythrocytes was increased in 8-wk-old offspring exposed to CY at 20 micrograms/g on d 17 of gestation. The T-lymphocyte parameters were relatively unaffected by in utero exposure to CY, suggesting either that cell-mediated immune function was not affected by treatment or that homeostasis was restored prior to immunologic evaluation of offspring.