The effect of moderate early gestation undernutrition on kidney glomerular number in fetal sheep

Braddick, L., Burrage, D., Cleal, J., Noakes, D., Hanson, M.A. and Green, L.R. (2007) The effect of moderate early gestation undernutrition on kidney glomerular number in fetal sheep. Proceedings of the Physiological Society, 6 (PC3).

Abstract

Poor in utero nutrition is implicated in the association between low birth weight and the development of hypertension in adulthood (Barker et al., 1989). It has been proposed that this association may result from impaired prenatal kidney growth and lower nephron endowment induced by suboptimal in utero nutrition (Brenner et al., 1988). In addition thinner mothers, which may indicate relatively poorer nutrition, tend to have fetuses that have kidneys that are relatively narrow for their length (Mukherjee et al., 2005). A 50% nutrient restriction from 1 to 31 days gestation (dGA, term ~147 dGA) alters renal and cardiovascular control in adult male sheep offspring (Cleal et al., 2004). This challenge is associated with altered blood pressure (BP) responses to angiotensin II but no changes in kidney size or function in late gestation fetuses (Braddick et al., 2006). The aim of the current study was to determine if fetal kidney structure is altered by early gestation undernutrition. Pregnant ewes were housed individually and fed 100% (C, n = 8) or 40% (R, n = 8) of their total nutrient requirements between 1 and 31 dGA, and 100% thereafter. All fetuses were singletons, the sex ratio was 1:1 in C and 5:3 in R groups. At post-mortem (127 dGA) the left kidney was perfusion fixed with formalin. Each kidney was cut in half and cut into 5 mm slices. Systematic sampling was used to select every 10th piece which was embedded in glycomethacylate resin. The selected blocks were sectioned at 2 µm, and every 200th and 210th pair were collected and stained with toluidine blue. The physical dissector technique was used to count the number of glomeruli in the cortex using by light microscopy. Data are mean ± SEM and were analysed by Student’s t-test. Fetal body (C = 2.91 ± 0.08; R = 2.92 ± 0.12 kg) and kidney weight (Right; C = 9.66 ± 0.61; R = 9.80 ± 0.40 g; Left; C = 11.65 ± 0.56; R = 11.33 ± 0.56 g) were similar in both groups. There was no significant difference in fetal glomerular number in the left kidney in R compared to C fetuses (C = 326,100 ± 40,850; R = 457,300 ± 118,700). Early gestation nutrition restriction did not alter fetal or organ growth or kidney development in late gestation sheep. Therefore altered renal and cardiovascular control in adult sheep following early gestation nutrient restriction is not due to altered glomerular number.

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Contributors

Author: J. Cleal

Author: M.A. Hanson

Author: L.R. Green

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