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Effects of prenatal and postnatal exposure to gentamicin on renal differentiation in the rat
Insights
Gentamicin exposure during pregnancy in rats reduced the number of nephrons (kidney filtering units) in offspring, potentially impacting kidney development. Postnatal exposure did not show the same effect on nephron count.
Area of Science:
- Nephrology
- Developmental Toxicology
- Pharmacology
Background:
- Gentamicin is an antibiotic commonly used to treat bacterial infections.
- Prenatal exposure to certain medications can impact fetal development.
- The effects of gentamicin on developing kidney structures require further investigation.
Purpose of the Study:
- To investigate the impact of prenatal gentamicin exposure on nephrogenesis and kidney development in rats.
- To compare the effects of in utero versus postnatal gentamicin exposure on the final nephron number.
Main Methods:
- Pregnant rats received daily gentamicin injections from day 10 of gestation until term.
- Offspring were assessed for growth retardation, nephron number, and kidney histology.
- A separate group of rats received postnatal gentamicin exposure.
Main Results:
- Prenatal gentamicin exposure resulted in growth-retarded pups with a significant reduction (≥20%) in both initial and final nephron counts.
- Focal tubular lesions were observed in the kidneys of pups exposed to gentamicin in utero.
- Postnatal gentamicin exposure, despite higher kidney concentrations, did not affect the final nephron number.
Conclusions:
- Prenatal gentamicin exposure adversely affects developing kidneys in rats, causing reduced nephrogenesis and tubular damage.
- The observed reduction in nephron number is likely linked to growth retardation, but a direct effect of gentamicin on early nephrogenesis cannot be excluded.
Abstract:
Pregnant rats were injected daily, from the 10th day of gestation to term, with 75 mg/kg of gentamicin. They gave birth about 15 h later than control pregnant rats injected with saline to pups with various degrees of growth retardation. In pups born of gentamicin-treated mothers, the number of nephrons present at birth, as well as the final number of nephrons, were reduced by at least 20%. Observation of the kidneys by light microscopy showed focal tubular lesions on the mature nephrons. The intrarenal concentration of gentamicin was higher in the severely growth retarded pups than in the others. In another series of experiments, rats were given 75 mg/kg of gentamicin daily from days 1 to 13 after birth. Although under these conditions the concentration of gentamicin reached in the postnatal kidney was higher than that reached after exposure in utero, no reduction of the final number of nephrons was observed. It is concluded that administration of gentamicin to pregnant rats caused focal tubular lesions in the developing kidney and a reduced rate of early nephrogenesis. The latter was probably due to growth retardation, though a more direct effect of gentamicin on early nephrogenesis may also have been involved.