THE INCIDENCE OF RENAL ANOMALIES AT FULL-TERM IN FETAL RATS IS SYNERGISTICALLY INCREASED BY ESTRADIOL (BUT NOT TESTOSTERONE) SUPPLEMENTATION ON DAY 18 OF ALCOHOLIC GESTATION

Background/Purpose: Fetal alcohol syndrome is characterized by facial dysmorphology, mental and growth retardation, and somatic anomalies in cluding hydronephrosis. The authors sought to determine the influence of exogenous testosterone or estradiol on the incidence of hydronephro sis in a rodent model of fetal alcohol syndrome (FAS). Methods: Pregna nt rats were fed a liquid diet containing 35% ethanol-derived calories from gestation day 6 through 15, With exogenous testosterone or estra diol supplementation on day 18. On day 20, fetal kidneys were examined for evidence of hydronephrosis, and fetal serum estradiol concentrati ons were determined by radioimmunoassay. Results: Maternal estrogen su pplementation resulted in very high fetal serum estradiol levels that were not additionally increased by alcoholism. Despite this fact, the expression of renal malformations was highest in the alcoholic, estrad iol-supplemented offspring. Additionally, the rate of renal malformati ons was significantly higher in the estrogen-supplemented alcoholic gr oup than in the strictly estradiol animals, yet the fetal serum estrad iol concentrations did not differ between the two groups. Conclusions: This suggests that ethanol may act synergistically with estradiol to increase the rate of renal anomalies including hydronephrosis. Such da mage may persist via a suppression of normal testosterone-stimulated r enal growth and development. FAS includes significant renal anomalies characterized by hydronephrosis in both animal models and affected chi ldren. Although the long-term functional sequelae of hydronephrosis an d reflux are well known, the progression of renal disease in FAS child ren remains to be documented. Copyright (C) 1997 by W.B. Saunders Comp any.