Differential effects of maternal nutrient restriction through pregnancy on kidney development and later blood pressure control in the resulting offspring

Abstract

The mechanisms whereby maternal nutritional manipulation through pregnancy result in altered blood pressure in the offspring may include changes in fetal and newborn and adult renal prostaglandin (PG) synthesis, metabolism, and receptor expression. Since the postnatal effects of nutrient restriction on the renal PG synthesis and receptor system during nephrogenesis in conjunction with nephron numbers and blood pressure have not been evaluated in the rat, the present study examined the effect of reducing maternal food intake by 50% of ad libitum through pregnancy on young male rats. Six control-fed mothers and eight nutrient-restricted pregnant rats with single litter mates were used at each sampling time point, most of which occurred during nephrogenesis. Offspring of nutrient-restricted dams were lighter from birth to 3 days. This was accompanied by reduced PGE2, with smaller kidneys up to 14 days. Nutrient restriction also decreased mRNA expression of the PG synthesis enzyme, had little effect on the PG receptors, and increased mRNA expression of the degradation enzyme during nephrogenesis and the glucocorticoid receptor in the adult kidney. These mRNA changes were normally accompanied by similar changes in protein. Nephron number was also reduced from 7 days up to adulthood when blood pressure (measured by telemetry) did not increase as much as in control offspring during the dark, active period. In conclusion, maternal nutrient restriction suppressed renal PG concentrations in the offspring, and this was associated with suppressed kidney growth and development and decreased blood pressure.

Fig. 1.

Effect of maternal nutrient restriction through pregnancy on maternal weight during pregnancy and pup growth over the first 21 days of lactation. A: pregnant rats were either fed ad libitum [control, closed symbols (n = 6)] or 50% of this amount [nutrient restricted (NR), open symbols (n = 8)]. Data are means ± SE. ^aSignificant difference between control and nutrient restricted. ^bTime points when nutrient-restricted maternal weight is significantly higher than at start. ^cTime points when nutrient-restricted maternal weight is significantly lower than at start. B: offspring were born to mothers that were fed either ad libitum [control, closed symbols (n = 6)] or 50% of this amount [NR, open symbols (n = 8)]. Data are means ± SE. *Significant differences between groups (P < 0.05).

Fig. 2.

Effect of maternal nutrient restriction through pregnancy on total nephron number in the resulting offspring. Offspring were born to mothers that were fed either ad libitum [control, closed bars (n = 6)] or 50% of this amount [NR, open bars (n = 8)]. Data are means ± SE. *Significant differences between groups (P < 0.05).

Fig. 3.

Effect of maternal nutrient restriction through pregnancy on 24-h systolic and diastolic blood pressure (A), mean blood pressure (B), and heart rate profiles (C) in the resulting male offspring as measured between 11 and 12 wk of age. Offspring were born to mothers that were fed either ad libitum [control, closed symbols (n = 6)] or 50% of this amount [nutrient restricted (NR), open symbols (n = 8)]. Data are means ± SE. *Significant differences between groups (P < 0.05).

Fig. 4.

Effect of maternal nutrient restriction on expression of prostaglandin endoperoxide H synthase-2 (PGHS-2) (A) and prostaglandin dehydrogenase (PGDH) (B) mRNA. Pregnant rats were fed either ad libitum [control, closed bars (n = 6)] or 50% of this amount [NR, open bars (n = 8)]. Bar graphs illustrate means with their standard errors. Significant differences between control and NR groups: *P < 0.05, and significant differences between ages in the same nutritional group of animals indicated by different superscripts: P < 0.05 (control, bold lowercase letters; NR, capital letters).

Fig. 5.

Effect of maternal nutrient restriction on expression of the prostaglandin receptors (A), EP₁ mRNA (B), EP₂ mRNA (C), EP₃ mRNA (D), EP₃ protein (E), EP₄ mRNA (F), and EP₄ protein (H). Pregnant rats were fed either ad libitum [control, closed bars (n = 6)] or 50% of this amount [NR, open bars (n = 8)]. Bar graphs illustrate means with their standard errors. Significant differences between control and NR groups: *P < 0.05; and significant differences between ages in the same nutritional group of animals indicated by different superscripts: P < 0.05 (control: bold lowercase letters; NR: capital letters).

Fig. 6.

Effect of maternal nutrient restriction on expression of glucocorticoid receptor (GCR) mRNA (A) and GCR protein (B). Bar graphs illustrate means with their standard errors. Pregnant rats were fed either ad libitum [control, closed bars (n = 6)] or 50% of this amount [NR, open bars (n = 8)]. Significant differences between control and nutrient restricted groups: *P < 0.05; and significant differences between ages in the same nutritional group of animals indicated by different superscripts: P < 0.05 (control: bold lowercase letters; NR: capital letters).