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EFFECT OF VARYING MATERNAL FOLATE STATUS AND DIETARY FOLATE INTAKE ON RESPONSE TO DIVERSE DEVELOPMENTAL TOXICANTS IN THE RAT
Citation:
ROGERS, J. M., C. S. LAU, J. E. ANDREWS, N. CHERNOFF, J. R. THIBODEAUX, B. D. BARBEE, AND B. E. GREY. EFFECT OF VARYING MATERNAL FOLATE STATUS AND DIETARY FOLATE INTAKE ON RESPONSE TO DIVERSE DEVELOPMENTAL TOXICANTS IN THE RAT. Presented at Teratology Society Meeting, St. Pete Beach, FL, June 25 - 30, 2005.
Description:
Periconceptional and early pregnancy folate supplements are associated with reduced recurrence and occurrence of birth defects in humans. This study was undertaken to assess the influence of maternal folate status and dietary folate intake on outcome of exposures to diverse teratogens during pregnancy in the rat. Six-week old female Sprague-Dawley rats were fed diets containing 2.0 (the RDI for pregnant rats), 1.0 (marginal) or 0.176 (low) mg folate/kg diet for five weeks, and were then bred with chow-fed males. Sperm-positive females were fed their respective diets throughout pregnancy, during which they were exposed to at least two dosage levels and a vehicle control of Tomudex (a folate analog), dichloroacetic acid (DCA, drinking water contaminant), ethylenethiourea (ETU, fungicide breakdown product), 5-fluorouracil (5-FU, a chemotherapeutic), or boric acid (BA, insecticide). Dosing regimens were based on previous studies, and the highest dosage levels were teratogenic. Dams were killed on gestation day 21 for standard teratologic evaluations. The low folate diet alone caused reduced maternal weight gain near term, reduced fetal weight and increased resorptions. In general, lower dietary folate was associated with reduced fetal weight and increased resorptions within treatment groups across the chemicals tested. Within dosage groups, the incidence of terata was increased with lower maternal folate intake for tomudex, 5-FU and DCA (specifically, the incidence of ventricular septal defects). While ETU and boric acid were teratogenic at the dosages tested, the incidence of terata was not affected by maternal folate intake. However, the observed increase in prenatal mortality with decreasing maternal dietary folate may have masked effects on the incidence of terata. Taken together the results of these studies demonstrate the importance of folate for normal pregnancy and development, and provide evidence that maternal folate status is an important determinant of the outcome of exposure to developmental toxicants. This abstract does not necessarily reflect EPA policy.