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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.

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Affiliation: School of Veterinary Medicine and Science.

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Maternal LP diet reduces the availability of ornithine in the fetal compartment and hepatic spermine concentration. A, B) Ornithine was measured in fetal plasma (A) and amniotic fluid (B) using gas chromatography-mass spectrometry (see Materials and Methods). C–E) The polyamines putrescine (C), spermidine (D), and spermine (E) were measured in lysates of fetal liver using high-performance liquid chromatography. Data are dot plots of data points from individual fetuses (A–E) with the line indicating the mean from each dietary treatment. Data were analyzed by the general linear mixed model for the fixed effects of diet, sex, and their interaction (ewe included as a random effect in the model) using Genstat 15. F) Linear discriminant plot generated after multivariate analysis of 18 amino acids in fetal plasma (circles representing 95% confidence interval around group means) conducted after normalization of data (by establishing z scores). NS, nonsignificant. Values of P < 0.05 were considered significant.
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Figure 2: Maternal LP diet reduces the availability of ornithine in the fetal compartment and hepatic spermine concentration. A, B) Ornithine was measured in fetal plasma (A) and amniotic fluid (B) using gas chromatography-mass spectrometry (see Materials and Methods). C–E) The polyamines putrescine (C), spermidine (D), and spermine (E) were measured in lysates of fetal liver using high-performance liquid chromatography. Data are dot plots of data points from individual fetuses (A–E) with the line indicating the mean from each dietary treatment. Data were analyzed by the general linear mixed model for the fixed effects of diet, sex, and their interaction (ewe included as a random effect in the model) using Genstat 15. F) Linear discriminant plot generated after multivariate analysis of 18 amino acids in fetal plasma (circles representing 95% confidence interval around group means) conducted after normalization of data (by establishing z scores). NS, nonsignificant. Values of P < 0.05 were considered significant.

Mentions: At d 65, neither maternal diet nor fetal sex had any effect on measures of fetal growth (weight and crown-rump length) or on the relative size of fetal organs (Table 3). Accordingly, measurements of the major fetal substrates for growth (glucose, lactate, amino acids) were unaltered by maternal diet or fetal sex, and hence sexes are combined (fetal plasma glucose, 0.74±0.09 vs. 0.84±0.08 mM; fetal plasma lactate, 4.52±0.21 vs. 5.14±0.18 mM; total amino acids, 3900±177 vs. 3643±177 μM for CP vs. LP, respectively). However, type rather than quantity of micronutrients was subtly altered by maternal diet; for example, fetal plasma glycine was increased by a maternal LP diet (Table 4), an effect most apparent in female fetuses (CP male, 450±34 vs. LP male 455±31 μM; CP female, 349±31 vs. LP female 499±32 μM), whereas the concentrations of proline and asparagine were significantly lower in the plasma of female vs. male fetuses, regardless of diet (Table 4). As expected from maternal nutritional status, urea concentration in the amniotic fluid was significantly reduced in LP vs. CP fetuses (3497±339 vs. 6916±351 μM; P<0.001). Due to complex, dependent interrelationships between amino acids in the fetal compartment, we used a multivariate statistical approach to reveal potential treatment effects: linear discriminant analysis of normalized (z scores) standard and nonstandard (e.g., ornithine) amino acids indicated a significant separation due to maternal diet (Fig. 2F), largely contributed by the significant reduction in ornithine in LP relative to CP fetuses (Fig. 2A, B). Further analysis of fetal hepatic polyamine concentrations (the major site for polyamine synthesis in the fetus) indicated a significant reduction in fetal liver spermine, but not putrescine or spermidine, in LP relative to CP fetuses (Fig. 2C–E).


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)

Maternal LP diet reduces the availability of ornithine in the fetal compartment and hepatic spermine concentration. A, B) Ornithine was measured in fetal plasma (A) and amniotic fluid (B) using gas chromatography-mass spectrometry (see Materials and Methods). C–E) The polyamines putrescine (C), spermidine (D), and spermine (E) were measured in lysates of fetal liver using high-performance liquid chromatography. Data are dot plots of data points from individual fetuses (A–E) with the line indicating the mean from each dietary treatment. Data were analyzed by the general linear mixed model for the fixed effects of diet, sex, and their interaction (ewe included as a random effect in the model) using Genstat 15. F) Linear discriminant plot generated after multivariate analysis of 18 amino acids in fetal plasma (circles representing 95% confidence interval around group means) conducted after normalization of data (by establishing z scores). NS, nonsignificant. Values of P < 0.05 were considered significant.
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Figure 2: Maternal LP diet reduces the availability of ornithine in the fetal compartment and hepatic spermine concentration. A, B) Ornithine was measured in fetal plasma (A) and amniotic fluid (B) using gas chromatography-mass spectrometry (see Materials and Methods). C–E) The polyamines putrescine (C), spermidine (D), and spermine (E) were measured in lysates of fetal liver using high-performance liquid chromatography. Data are dot plots of data points from individual fetuses (A–E) with the line indicating the mean from each dietary treatment. Data were analyzed by the general linear mixed model for the fixed effects of diet, sex, and their interaction (ewe included as a random effect in the model) using Genstat 15. F) Linear discriminant plot generated after multivariate analysis of 18 amino acids in fetal plasma (circles representing 95% confidence interval around group means) conducted after normalization of data (by establishing z scores). NS, nonsignificant. Values of P < 0.05 were considered significant.
Mentions: At d 65, neither maternal diet nor fetal sex had any effect on measures of fetal growth (weight and crown-rump length) or on the relative size of fetal organs (Table 3). Accordingly, measurements of the major fetal substrates for growth (glucose, lactate, amino acids) were unaltered by maternal diet or fetal sex, and hence sexes are combined (fetal plasma glucose, 0.74±0.09 vs. 0.84±0.08 mM; fetal plasma lactate, 4.52±0.21 vs. 5.14±0.18 mM; total amino acids, 3900±177 vs. 3643±177 μM for CP vs. LP, respectively). However, type rather than quantity of micronutrients was subtly altered by maternal diet; for example, fetal plasma glycine was increased by a maternal LP diet (Table 4), an effect most apparent in female fetuses (CP male, 450±34 vs. LP male 455±31 μM; CP female, 349±31 vs. LP female 499±32 μM), whereas the concentrations of proline and asparagine were significantly lower in the plasma of female vs. male fetuses, regardless of diet (Table 4). As expected from maternal nutritional status, urea concentration in the amniotic fluid was significantly reduced in LP vs. CP fetuses (3497±339 vs. 6916±351 μM; P<0.001). Due to complex, dependent interrelationships between amino acids in the fetal compartment, we used a multivariate statistical approach to reveal potential treatment effects: linear discriminant analysis of normalized (z scores) standard and nonstandard (e.g., ornithine) amino acids indicated a significant separation due to maternal diet (Fig. 2F), largely contributed by the significant reduction in ornithine in LP relative to CP fetuses (Fig. 2A, B). Further analysis of fetal hepatic polyamine concentrations (the major site for polyamine synthesis in the fetus) indicated a significant reduction in fetal liver spermine, but not putrescine or spermidine, in LP relative to CP fetuses (Fig. 2C–E).

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