Nephrotoxin exposure in utero reduces glomerular number in sclerosis-pronebut not sclerosis-resistant mice

Background. We have previously found that nephron number was not fixed, tha t is, there was a direct correlation between low birth weight and decreased nephron number in infants. In sclerosis-prone rats, we found that gentamic in exposure in utero induced a reduction in glomerular number and aggravate d glomerulosclerosis in adults. In mice, we found that an inborn 50% reduct ion in nephron number, caused by the Os mutation, was associated with glome rulosclerosis in sclerosis-prone (ROPS+/+) mice, but not in sclerosis-resis tant (C57BL/6J) mice. Because the genetic background determined the respons e to decreased nephron number, we asked whether the susceptibility changes in glomerular number and glomerulosclerosis were linked. Methods. Gentamicin was administered before and after the onset of fetal ne phrogenesis. (1) Prior to the onset of nephrogenesis, two groups of pregnan t mice were treated from embryonic day (E) E8 to E12. In group A, early glo merular development was studied by placing ureteric ridges removed on E12 i n vitro for four days, following which the ureteric bud branches and glomer uli were counted using lectin staining. In group B, nephron number was dete rmined in spontaneously delivered 14-day-old (14PN) pups by counting glomer uli. (2) After the onset of nephrogenesis, to determine the direct effects of gentamicin on nephron induction, ureteric ridges were placed in organ cu lture at E12 of normal gestation, in the presence or absence of gentamicin. The number of glomeruli and ureteric bud branches were counted after six d ays in culture. Results. A decrease in glomerular number and ureteric bud branches was obse rved in sclerosis-prone (ROP+/+) mice, irrespective of whether gentamicin w as administered prior to or after the onset of nephrogenesis. Glomerular nu mber and ureteric bud branching were not decreased by gentamicin in scleros is-resistant (C57BL/6) mice.