Intrauterine growth retardation (IUGR) was induced in Sprague-Dawley rats by partial artery ligation of one uterine horn in the mother on day 17 of gestation or by feeding the mother a 5% protein diet from day 8 of gestation. The controls were pups of the contralateral uterine horn or pups born to mothers fed a normal (22%) protein diet. The number of nephrons present at birth and the final number of nephrons in 2-week-old rats were counted throughout the entire kidney. The number of nephrons present at birth and the final number of nephrons were significantly correlated with birth weight for growth-retarded rats of both groups and their corresponding controls (P < 0.02 for the poorest correlation). Clearance experiments and morphometric studies of 2-week-old rats born to mothers with uterine artery ligation indicated that, despite a large compensatory hypertrophy of the nephrons in those animals born with a nephron deficit of about 30%, the overall renal function was impaired. We conclude that IUGR is accompanied by a nephron deficit which may not be fully compensated for within the first weeks after birth.

We conclude that vitamin A supply to the fetus is critical in determining the number of nephrons. Data available thus far on the frequency of mild VAD during pregnancy and on the long-term consequences of inborn nephron deficit highlight the clinical relevance of the present study.

Congenital malformations occur more frequently in the offspring of diabetic mothers. These in vivo and in vitro studies investigate the potential adverse effects of hyperglycemia on kidney development in the rat. Female rats were made hyperglycemic throughout gestation with a single injection of streptozotocin (STZ) on day 0 of gestation, or for a short period encompassing the early stage of renal organogenesis by infusing glucose from gestational days 12-16. Kidney development in the pups was assessed by determining the total number of nephrons formed in the kidney. The number of nephrons was significantly reduced (10-35%) in the pups from STZ-treated dams, as a function of hyperglycemia. There were also fewer nephrons in pups from dams given glucose infusion whose hyperglycemia was transiently higher on day 13 of gestation. The in vitro experiments were done on metanephroi removed from 14-day-old fetuses and grown for 6 days in medium containing 0, 6.9, 13.8, or 27.5 mmol/l glucose. The development of explants grown in 0, 13.8, and 27.5 mmol/l glucose was impaired compared with that of explants grown in the 6.9 mmol/l control medium, showing that the glucose concentration must be closely controlled to ensure optimum in vitro metanephros development. Thus, exposure to hyperglycemia in utero can cause a nephron deficit, which in turn may have renal consequences later in life.