Effects of dietary protein restriction on nephron number in the mouse

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In rats, maternal protein restriction reduces nephron endowment and often leads to adult hypertension. Sex differences in these responses have been identified. The molecular and genetic bases of these phenomena can best be identified in a mouse model, but effects of maternal protein restriction on kidney development have not been examined in mice. Therefore, we determined how combined prenatal and postnatal protein restriction in mice affects organ weight, glomerular number and dimensions and renal expression of angiotensin receptor mRNA, in both male and female offspring. C57/Bl6/129sv mice received either a normal (20 w/w; NP) or low (9 w/w; LP) protein diet during gestation and postnatal life. Offspring were examined at postnatal day 30. Protein restriction retarded growth of the kidney, liver, spleen, heart and brain. All organs except the brain weighed less in female than male offspring. Protein restriction increased normalized (to body weight) brain weight, with females having relatively heavier brains than males. The effects of protein restriction were not sex-dependent, except that normalized liver weight was reduced in males but increased in females. Glomerular volume, but not number, was greater in female than male mice. Maternal protein restriction reduced nephron endowment similarly in male and female mice. Renal expression of AT1A receptor mRNA was 6-fold greater in female than male NP mice, but similar in male LP and female LP mice. We conclude that maternal protein restriction reduces nephron endowment in mice. This effect provides a basis for future studies of developmental programming in the mouse. Key words: nephron deficit, sex, kidney, stereology, mice.
Original languageEnglish
Pages (from-to)R1768 - R1774
Number of pages7
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number5
Publication statusPublished - 2007

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