Uninephrectomy and repetitive pregnancies in mice: A combined stimulus for renal hypertrophy

Three hundred 7-week-old Beit Dagan female mice underwent right nephrectomy, or sham operation, and either remained virgin or were exposed to six repetitive pregnancies. Fractional kidney weight, dry weight and protein content were determined at ages 9, 10, 11, 17 and 26 weeks corresponding to the ends of the first, second and third trimester of the first pregnancy and completion of the third and sixth pregnancies respectively. In addition histological sections were evaluated morphologically and morphometrically. Renal dry weight and protein content per kidney increased abruptly to maximal values a week after nephrectomy and remained stable thereafter. Repetitive pregnancies were associated with progressive increments in both parameters. The effects of unilateral nephrectomy and repetitive pregnancy were additive. Following unilateral nephrectomy or pregnancy the number of glomeruli per field, as well as fractional glomerular area, increased more rapidly than in sham-operated virgin controls. However, the maximal glomerular number or fractional area attained did not differ from control values.We conclude that (a) in 8-week-old mice pregnancy is associated with renal cell hypertrophy; (b) repetitive pregnancies in these animals produce progressive augmentation in both renal dry weight and protein content; (c) the effects of repetitive pregnancy and unilateral nephrectomy on renal cell hypertrophy are additive; (d) this would indicate that neither manoeuvre exhausts maximal renal capacity for cell hypertrophy, and would suggest some possibilities for the underlying mechanisms.