Interrelationship between renal mass and renotropin activity in consecutive generations of uninephrectomized mice

In offspring of uninephrectomized mouse mothers at ages 3, 5 and 7 weeks (n = 8 in each group) fresh and dry kidney weights, protein content, mean number of glomeruli per microscopic field (GN), mean cumulative fractional glomerular area per microscopic field (GA) and mean number of nuclei per glomerulus (GC) were all significantly increased compared to age-matched control offspring of sham nephrectomized mothers. Sera from mice at ages 3 and 5 weeks, offspring of uninephrectomized mothers, stimulated mesangial cell proliferation in culture. Surprisingly, fresh and dry renal weight, GN, GA and GC were all significantly increased in offspring of sham nephrectomized mothers, daughters of uninephrectomized grandmothers. We speculate that elevated maternal renotropin transferred via the placenta introduces a modification in the embryonal interrelationship between renal mass and endogenous renotropin. This modification results in exaggerated embryonal serum renotropic activity extending to puberty. Whether the humoral agent responsible for enhanced mesangial cell proliferation in vitro is identical to renotropin remains to be elucidated.