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Studies on the effects of gentamicin on rat metanephric development in vitro
Author(s) -
Cullen Luise A,
Young Richard J,
Bertram John F
Publication year - 2000
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1046/j.1440-1797.2000.00512.x
Subject(s) - nephron , gentamicin , medicine , endocrinology , in vivo , mesenchyme , duct (anatomy) , kidney , anatomy , biology , epithelium , pathology , antibiotics , biochemistry , microbiology and biotechnology
SUMMARY: Reduced nephron endowment has been associated with increased risk of developing essential hypertension and chronic renal failure. Both in vivo and in vitro exposure of developing rat metanephroi to gentamicin has been reported to inhibit metanephric development resulting in reduced nephron endowment. The aim of the present study was to confirm that gentamicin results in reduced nephron endowment in vitro , and to extend understanding of the mechanisms responsible for this reduced endowment. Embryonic day 14 (E14) rat metanephroi were cultured for up to 4 days in serum‐free medium with or without 50 μg/mL gentamicin. Metanephroi cultured in the presence of gentamicin were 25% smaller than control metanephroi after 2 days culture and 30% smaller after 4 days ( P < 0.001). This decrease in total metanephric volume was reflected in reduced volumes of ureteric duct epithelium, mesenchyme/interstitium and nephron epithelia. The reduced volume of ureteric duct epithelium in gentamicin‐treated metanephroi was associated with a 30% reduction in the number of ureteric duct branch points at 2 days. Metanephroi cultured with gentamicin contained 20% fewer glomeruli than control metanephroi ( P < 0.005) at 4 days. These glomeruli were 30% smaller than control glomeruli ( P < 0.05). Qualitative observations of Pax‐2 immunostained mesenchymal condensates indicated no difference in condensate size, location or morphology. These results confirm that in vitro exposure of developing rat metanephroi to gentamicin results in reduced nephron endowment. The defect in nephrogenesis centres around the inhibition of ureteric duct branching.