Comparative aspects of fetal renal development

Wintour, E. M.; Moritz, Karen M.

doi:10.1111/j.2042-3306.1997.tb05078.x

Cited by 22 publications

(6 citation statements)

References 113 publications

(71 reference statements)

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“…17 g crude protein·MJ ME (metabolic energy). At day 65 gestation, chosen to coincide with peak nephrogenesis in the sheep (Wintour & Moritz, 1997), a proportion of CP (n=7) and LPE (n=9) ewes were euthanised and fetal kidneys snap frozen in liquid nitrogen and stored at −80°C for further analysis. The remainder (CP, n=6; LPE, n=7; LPL, n=6) carried to term and the singleton offspring were delivered naturally.…”

Section: Methodsmentioning

confidence: 99%

“…Increased focus on diet during a woman’s (or man’s (Carone et al ., 2010; Ng et al ., 2010)) reproductive years, particularly during pregnancy and lactation, has been stimulated by the Developmental Origins of Health and Disease hypothesis (Barker & Osmond, 1986; Gluckman et al ., 2008) where individual variability in fetal response to maternal malnutrition (reflected as disproportionate growth (Barker et al ., 2005) and/or low birth weight (Barker & Osmond, 1988)) increases risk of those individuals developing hypertension (Huang et al ., 2010), coronary dysfunction (Crispi et al ., 2010), Type 2 Diabetes (Whincup et al ., 2008) and kidney disease (Woods et al ., 2004; Amann et al ., 2006) later in life. Increased focus on the latter is particularly pertinent as nephrogenesis is complete by term in Man and non-litter bearing mammals (Wintour & Moritz, 1997) and is therefore particularly sensitive and vulnerable to maternal malnutrition. For example, a maternal low protein, high glucose or high fat diet may reduce nephron endowment (Vehaskari et al ., 2001; Nehiri et al ., 2008; Tran et al ., 2008).…”

Section: Introductionmentioning

confidence: 99%

“…There is a considerable body of evidence in laboratory rodents and in larger animals, such as the sheep, that early maternal diet can influence renal structure of the adult offspring (McMillen & Robinson, 2005; Ojeda et al ., 2008; Moritz et al ., 2009; Puddu et al ., 2009). Sheep are particularly relevant for such studies as the start and end periods of nephrogenesis (meso/metanephros) are virtually identical to Man, ending at ~0.90 gestation (Wintour & Moritz, 1997; Moritz & Wintour, 1999). Prenatal undernutrition of sheep increases blood pressure and decreases nephron number of the adolescent offspring (Gilbert et al ., 2005), while a double-hit i.e.…”

Section: Introductionmentioning

confidence: 99%

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Protein‐energy malnutrition during early gestation in sheep blunts fetal renal vascular and nephron development and compromises adult renal function

Lloyd

Foster

Rhodes

et al. 2011

The Journal of Physiology

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Non-technical summaryA poor diet during pregnancy has been linked to long-term health outcomes for the baby, such as an increased risk of diseases of the heart and kidney. We show in an experimental model that recreates a poor diet during pregnancy, i.e. a diet low in protein with adequate energy, that kidney development in the baby is affected in such a way as to reduce the potential for new blood vessels to form. This results in a greater number of important, functional kidney cells spontaneously dying. Later in life, these effects in the kidney manifest as permanently reduced kidney function, especially if the baby subsequently becomes overweight as an adult. The research reinforces advice to pregnant mothers about the importance of eating a nutritionally balanced diet during pregnancy.AbstractA nutritionally poor maternal diet can reduce nephron endowment and pre-empt premature expression of markers for chronic renal disease in the offspring. A mechanistic pathway from variation in maternal diet through altered fetal renal development to compromised adult kidney structure and function with adult-onset obesity has not been described. We show that maternal protein-energy malnutrition in sheep blunts nephrogenic potential in the 0.44 gestation (65 days gestation, term ∼147 days) fetus by increasing apoptosis and decreasing angiogenesis in the nephrogenic zone, effects that were more marked in male fetuses. As adults, the low-protein-exposed sheep had reduced glomerular number and microvascular rarefaction in their kidneys compensated for, respectively, by glomerular hypertrophy and increased angiogenic support. In this study, the long-term mild anatomical deficits in the kidney would have remained asymptomatic in the lean state, but when superimposed on the broad metabolic challenge that obesity represents then microalbuminuria and blunted bilateral renal function revealed a long-term physiological compromise, that is only predicted to worsen with age. In conclusion, maternal protein-energy malnutrition specifically impacts fetal kidney vascular development and prevents full functionality of the adult kidney being achieved; these residual deficits are predicted to significantly increase the expected incidence of chronic kidney disease in prenatally undernourished individuals especially when coupled with a Western obesogenic environment.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Protein‐energy malnutrition during early gestation in sheep blunts fetal renal vascular and nephron development and compromises adult renal function

Lloyd

Foster

Rhodes

et al. 2011

The Journal of Physiology

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“…In this study, we were interested in how maternal PEM may influence nutrient patterns in the fetal compartment, but we were specifically interested in effects on the fetal ornithine cycle: PEM is likely to reduce maternal plasma urea through reduced protein turnover, the molar mass of urea (60 g/mol) is such that it easily crosses the placental barrier, and the urea/ornithine cycle delivers considerable substrate for polyamine synthesis, an important precursor of cell proliferation. Furthermore, investigation of prenatal factors that can negatively affect kidney development is of particular merit: the mammalian kidney has acquired its full complement of nephrons at, or shortly after, birth ( 39 , 40 ), a limited capacity for repair after injury ( 41 ), and no clearly defined stem cell niche to replace lost functional units such as glomeruli ( 42 ). Hence, the kidney, much like the ovary, accommodates by having a large reserve functional capacity ( i.e.…”

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confidence: 99%

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

et al. 2014

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This paper identifies a common nutritional pathway relating maternal through to fetal protein-energy malnutrition (PEM) and compromised fetal kidney development. Thirty-one twin-bearing sheep were fed either a control (n=15) or low-protein diet (n=16, 17 vs. 8.7 g crude protein/MJ metabolizable energy) from d 0 to 65 gestation (term, ∼145 d). Effects on the maternal and fetal nutritional environment were characterized by sampling blood and amniotic fluid. Kidney development was characterized by histology, immunohistochemistry, vascular corrosion casts, and molecular biology. 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. Maternal PEM specifically impacts the fetal ornithine cycle, affecting cellular polyamine metabolism and microvascular development of the fetal kidney, effects that likely underpin programming of kidney development and function by a maternal low protein diet.—Dunford, L. J., Sinclair, K. D., Kwong, W. Y., Sturrock, C., Clifford, B. L., Giles, T. C., Gardner, D. S.. Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development.

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“…Its osmolality and sodium concentration decrease, an effect thought to be a result of the production of dilute fetal urine. It has been well demonstrated that the fetal urine becomes increasingly hypotonic relative to the fetal plasma as gestation progresses, due to the relatively large glomerular filtration for the renal blood flow in the fetal metanephros 7 . Parallel to the decrease in osmolality, the urea, creatinine and uric acid contents of the AF increase during the second half of pregnancy 8 .…”

Section: Role Of the Amniotic Fluidmentioning

confidence: 99%

Management of severe oligohydramnios with antepartum transabdominal amnioinfusion

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Comparative aspects of fetal renal development

Cited by 22 publications

References 113 publications

Protein‐energy malnutrition during early gestation in sheep blunts fetal renal vascular and nephron development and compromises adult renal function

Protein‐energy malnutrition during early gestation in sheep blunts fetal renal vascular and nephron development and compromises adult renal function

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

Management of severe oligohydramnios with antepartum transabdominal amnioinfusion

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