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.
OBJECTIVE
Fetal alcohol syndrome is characterized by facial dysmorphology, mental and growth retardation, and somatic anomalies including hydronephrosis. The authors sought to determine the influence of exogenous testosterone or estradiol on the incidence of hydronephrosis in a rodent model of fetal alcohol syndrome (FAS).


METHODS
Pregnant rats were fed a liquid diet containing 35% ethanol-derived calories from gestation day 6 through 15, with exogenous testosterone or estradiol supplementation on day 18. On day 20, fetal kidneys were examined for evidence of hydronephrosis, and fetal serum estradiol concentrations were determined by radioimmunoassay.


RESULTS
Maternal estrogen supplementation 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, estradiol-supplemented offspring. Additionally, the rate of renal malformations was significantly higher in the estrogen-supplemented alcoholic group than in the strictly estradiol animals, yet the fetal serum estradiol 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 damage may persist via a suppression of normal testosterone-stimulated renal growth and development. FAS includes significant renal anomalies characterized by hydronephrosis in both animal models and affected children. Although the long-term functional sequelae of hydronephrosis and reflux are well known, the progression of renal disease in FAS children remains to be documented.
Calvano
C J
CJ
Department of Pharmacology, Albany Medical College, NY 12208, USA.
LeFevre
R
R
Mankes
R F
RF
Reddy
P P
PP
Moran
M E
ME
Hoar
R M
RM
Mandell
J
J
D000818:Animals; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004357:Drug Synergism; D004958:Estradiol / Q000009:adverse effects* / Q000097:blood; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000150:complications*; D006869:Hydronephrosis / Q000097:blood / Q000139:chemically induced / Q000209:etiology*; D015994:Incidence; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000009:adverse effects* / Q000097:blood
D013739:Testosterone; D004958:Estradiol