ALTERATIONS IN THE DEVELOPING IMMUNE-SYSTEM OF THE F344 RAT AFTER PERINATAL EXPOSURE TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN .1. EFFECTS ON THE FETUS AND THE NEONATE

Perinatal exposure of rodents to 2,3,7,8-tetrachlorodibenzo-p-dioxin ( TCDD) has been shown to result in thymic atrophy and cell-mediated imm une suppression at lower doses than are required to produce those effe cts following adult exposure. This study was designed to examine the e ffects that in utero TCDD exposure has on thymocyte development in the rat. Timed-bred pregnant F344 rats were given 0, 1.0, or 3.0 mu g TCD D/kg body weight by gavage on gestational day 14 (GD14). On GD19 or GD 22/postnatal day one (PD1), the dams were euthanized, and the dams and their offspring were examined for organ weight and thymus phenotypic alterations. GD19 fetuses from the 3.0 mu g TCDD/kg maternal exposure group exhibited decreases in relative thymus weight and thymic cellula rity. There were a decreased percentage of CD3(-)/CD4(+)CD8(+) thymocy tes and an increased percentage of CD3(-)/CD4-CD8+ thymocytes in these fetuses, but there were no alterations in the CD3(+) subsets. No effe cts were seen in the GD19 fetuses from the 1.0 mu g TCDD/kg dosage gro up. In the TCDD-exposed GD22/PD1 offspring thymic atrophy was no longe r present, but there was an increase in the relative liver weight. In addition, there were decreased percentages of CD3(-)/CD4(-)CD8(-), CD3 (+)/CD4(-)CD8(-), and CD3(+)/CD4(+)CD8(+) thymocytes and an increased percentage of CD3(+)/CD4(-)CD8(+) thymocytes. The CD3(+)/CD4(-)CD8(-) and CD3(+)/CD4(-)CD8(+) cell populations were the most sensitive, with changes appearing at both 1.0 and 3.0 mu g TCDD/kg maternal exposures . The TCDD-exposed GD19 dams exhibited an increased relative liver wei ght, a decreased relative thymus weight, and alterations in thymic CD3 (+) populations. Three days later the relative organ weights had recov ered in the dams, but the phenotypic alterations were seen in CD3(-) a s well as CD3(+) thymocyte subsets. These results indicate that the de veloping rat fetal thymus is susceptible to the effects of TCDD. In ad dition, pregnant rats and their offspring showed similar alterations i n thymocytic phenotypes. (C) 1997 Elsevier Science Ireland Ltd.