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Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development.

Dunford LJ, Sinclair KD, Kwong WY, Sturrock C, Clifford BL, Giles TC, Gardner DS - FASEB J. (2014)

Bottom Line: PEM had little measureable effect on maternal and fetal macronutrient balance (glucose, total protein, total amino acids, and lactate were unaffected) or on fetal growth.PEM decreased maternal and fetal urea concentration, which blunted fetal ornithine availability and affected fetal hepatic polyamine production.For the first time in a large animal model, we associated these nutritional effects with reduced micro- but not macrovascular development in the fetal kidney.

View Article: PubMed Central - PubMed

Affiliation: School of Veterinary Medicine and Science.

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Fetal kidney angiogenic potential, measured as VEGFA, is blunted by maternal LP diet. Fetal kidney angiogenic potential was indirectly determined using immunohistochemistry and quantification of cells positive for VEGFA. A) Representative micrograph of the nephrogenic zone: VEGFA staining is brown; white arrows indicate developing collecting ducts. B) Dot plot of individual data points for control and LP-exposed fetuses (control: male, n=8; females n=7; LP diet: male, n=8; female, n=8). C) Positive control, mouse kidney. D, E) Negative controls, omission of primary antibody (D) and rabbit IgG isotype control (E). All micrographs were taken at ×200. Data were analyzed by the general linear mixed model for the fixed effects of diet, sex, and their interaction term (diet×sex) using Genstat 15. NS, nonsignificant. Values of P < 0.05 were considered significant.
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Figure 5: Fetal kidney angiogenic potential, measured as VEGFA, is blunted by maternal LP diet. Fetal kidney angiogenic potential was indirectly determined using immunohistochemistry and quantification of cells positive for VEGFA. A) Representative micrograph of the nephrogenic zone: VEGFA staining is brown; white arrows indicate developing collecting ducts. B) Dot plot of individual data points for control and LP-exposed fetuses (control: male, n=8; females n=7; LP diet: male, n=8; female, n=8). C) Positive control, mouse kidney. D, E) Negative controls, omission of primary antibody (D) and rabbit IgG isotype control (E). All micrographs were taken at ×200. Data were analyzed by the general linear mixed model for the fixed effects of diet, sex, and their interaction term (diet×sex) using Genstat 15. NS, nonsignificant. Values of P < 0.05 were considered significant.

Mentions: The macrovascular structure of the fetal kidneys was directly assessed using vascular corrosion casting, which produced a detailed 3D representation of the major vessels in the fetal kidneys at 65 d gestation (Fig. 3A). Micro-computed tomography (micro-CT) of corrosion casts indicated no effect of maternal diet nor fetal sex on cast volume (pooled sexes, Fig. 3B) or surface area (882±156 vs. 1069±135 mm2 for control vs. low protein, respectively; P=0.40), but each was highly correlated (R2=0.97; P<0.001). In contrast, the microvascular density of the fetal kidneys (assessed indirectly by IHC staining of CD34 and VEGFA) was significantly blunted in LP-exposed vs. CP fetuses (CD34, Fig. 4; VEGFA, Fig. 5), particularly in the nephrogenic zone of the kidney. Analysis at the transcript level (qPCR) complemented the protein data with respect to blunted microvascular developmental potential in the kidney of LP-exposed fetuses (Table 5).


Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development.

Dunford LJ, Sinclair KD, Kwong WY, Sturrock C, Clifford BL, Giles TC, Gardner DS - FASEB J. (2014)

Fetal kidney angiogenic potential, measured as VEGFA, is blunted by maternal LP diet. Fetal kidney angiogenic potential was indirectly determined using immunohistochemistry and quantification of cells positive for VEGFA. A) Representative micrograph of the nephrogenic zone: VEGFA staining is brown; white arrows indicate developing collecting ducts. B) Dot plot of individual data points for control and LP-exposed fetuses (control: male, n=8; females n=7; LP diet: male, n=8; female, n=8). C) Positive control, mouse kidney. D, E) Negative controls, omission of primary antibody (D) and rabbit IgG isotype control (E). All micrographs were taken at ×200. Data were analyzed by the general linear mixed model for the fixed effects of diet, sex, and their interaction term (diet×sex) using Genstat 15. NS, nonsignificant. Values of P < 0.05 were considered significant.
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Related In: Results  -  Collection

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Figure 5: Fetal kidney angiogenic potential, measured as VEGFA, is blunted by maternal LP diet. Fetal kidney angiogenic potential was indirectly determined using immunohistochemistry and quantification of cells positive for VEGFA. A) Representative micrograph of the nephrogenic zone: VEGFA staining is brown; white arrows indicate developing collecting ducts. B) Dot plot of individual data points for control and LP-exposed fetuses (control: male, n=8; females n=7; LP diet: male, n=8; female, n=8). C) Positive control, mouse kidney. D, E) Negative controls, omission of primary antibody (D) and rabbit IgG isotype control (E). All micrographs were taken at ×200. Data were analyzed by the general linear mixed model for the fixed effects of diet, sex, and their interaction term (diet×sex) using Genstat 15. NS, nonsignificant. Values of P < 0.05 were considered significant.
Mentions: The macrovascular structure of the fetal kidneys was directly assessed using vascular corrosion casting, which produced a detailed 3D representation of the major vessels in the fetal kidneys at 65 d gestation (Fig. 3A). Micro-computed tomography (micro-CT) of corrosion casts indicated no effect of maternal diet nor fetal sex on cast volume (pooled sexes, Fig. 3B) or surface area (882±156 vs. 1069±135 mm2 for control vs. low protein, respectively; P=0.40), but each was highly correlated (R2=0.97; P<0.001). In contrast, the microvascular density of the fetal kidneys (assessed indirectly by IHC staining of CD34 and VEGFA) was significantly blunted in LP-exposed vs. CP fetuses (CD34, Fig. 4; VEGFA, Fig. 5), particularly in the nephrogenic zone of the kidney. Analysis at the transcript level (qPCR) complemented the protein data with respect to blunted microvascular developmental potential in the kidney of LP-exposed fetuses (Table 5).

Bottom Line: PEM had little measureable effect on maternal and fetal macronutrient balance (glucose, total protein, total amino acids, and lactate were unaffected) or on fetal growth.PEM decreased maternal and fetal urea concentration, which blunted fetal ornithine availability and affected fetal hepatic polyamine production.For the first time in a large animal model, we associated these nutritional effects with reduced micro- but not macrovascular development in the fetal kidney.

View Article: PubMed Central - PubMed

Affiliation: School of Veterinary Medicine and Science.

Show MeSH
Related in: MedlinePlus