Fetal hematopoietic alterations after maternal exposure to ethylene glycol monomethyl ether: prolymphoid cell targeting.Toxicol Appl Pharmacol. 1994 Nov; 129(1):53-60.TA
Ethylene glycol monomethyl ether (EGME), which is extensively used in the chemical industries, has been associated with hematologic disorders in both humans and experimental animals. EGME is metabolized to the active compound methoxy-acetic acid (MAA), which readily crosses the placenta and impairs fetal development. However, little is known about the effect of maternal EGME exposure on the development of fetal immunity. In the present report, in utero treatment with EGME was found to alter expression of murine thymocyte and liver fetal cell-surface markers. Pregnant mice were exposed to 100, 150, or 200 mg/kg EGME from gestational days (gd) 10 to 17 and offspring examined on gd 18. Significant thymic atrophy and cellular depletion were found in EGME-exposed fetal mice. Flow cytometric analysis indicated that EGME treatment resulted in decreased percentages of CD4+8+ thymocytes and increased percentages of CD4-8- thymocytes. In vitro exposure to MAA did not result in decreased thymocyte viability or proliferation. These data suggest that EGME, in addition to producing thymic hypocellularity, may inhibit thymocyte maturation. EGME also reduced the percentage of CD45+ leukocytic cells present in fetal liver, an alteration that appeared to be largely manifested by decreased numbers of CD45R+ and CD44dim prolymphoid cells. In vitro MAA exposure of fetal liver cells enriched for lymphoid precursors resulted in significant inhibition of proliferation. Reconstitution of irradiated hosts with gd 18 fetal liver cells from vehicle and EGME-exposed syngeneic donors demonstrated impaired ability of the EGME-treated fetal liver to repopulate the host spleen with B or T lymphocytes. These data suggest that EGME-induced immunosuppression may result from targeting of multiple hematopoietic compartments. Further, the present data indicate that fetal liver prolymphocytes may represent sensitive targets of EGME exposure.