Immediate and long-term renal effects of fetal exposure to gentamicin.
Aminoglycoside antibiotics, like gentamicin, given to pregnant females cross the placenta and accumulate in the fetal kidney, which, like the adult kidney, was found to be the major site of deposition. In young guinea-pigs whose mothers were given gentamicin during the week following nephrogenesis in the fetus, nephron growth was found to be retarded temporarily. In rats whose mothers were given gentamicin during the period of fetal nephrogenesis, the final number of nephrons was reduced by about 20%. In both cases, renal development was impaired, although the concentration of gentamicin in the fetal kidney was lower than that measured in the kidney of human fetuses whose mothers had received a single injection of aminoglycoside. In rats exposed to gentamicin in utero, cellular damage of the undifferentiated and differentiating renal tissues was observed. It is, there are likely that the oligonephronia observed in animals born of gentamicin-treated mothers resulted from a direct effect of the drug at early stages of nephrogenesis. When gentamicin administration to the mother was prolonged, part of the oligonephronia observed at birth might have also resulted from fetal growth retardation, secondary to adverse effects of the drug on the mother. Providing it was not associated with fetal growth retardation, the presence of high gentamicin concentrations in the fetal kidney at late stages of nephrogenesis did not affect nephron differentiation. Long-term studies of rats born with gentamicin-induced oligonephronia showed that neither the antibiotic still present in kidney several weeks after birth, nor the injuries it caused, prevented renal growth and morphological adaptation of the nephrons to their reduced number.(ABSTRACT TRUNCATED AT 250 WORDS)
Gilbert
T
T
Unité de Recherches sur le Développment Normal et Pathologique des Fonctions Epithéliales, INSERM U 319 Université Paris, France.
Lelievre-Pegorier
M
M
Merlet-Benichou
C
C
D005260:Female; D005333:Fetus / Q000187:drug effects*; D005839:Gentamicins / Q000009:adverse effects*; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013997:Time Factors
D005839:Gentamicins