The magnitude of nephron number reduction mediates intrauterine growth-restriction-induced long term chronic renal disease in the rat. A comparative study in two experimental models.

Background: Intrauterine growth restriction (IUGR) is a risk factor for hypertension (HT) and chronic renal disease (CRD). A reduction in the nephron number is proposed to be the underlying mechanism; however, the mechanism is debated. The aim of this study was to demonstrate that IUGR-induced HT and CRD are linked to the magnitude of nephron number reduction, independently on its cause.

Long Lasting Microvascular Tone Alteration in Rat Offspring Exposed In Utero to Maternal Hyperglycaemia.

Epidemiologic studies have demonstrated that cardiovascular risk is not only determined by conventional risk factors in adulthood, but also by early life events which may reprogram vascular function. To evaluate the effect of maternal diabetes on fetal programming of vascular tone in offspring and its evolution during adulthood, we investigated vascular reactivity of third order mesenteric arteries from diabetic mother offspring (DMO) and control mother offspring (CMO) aged 3 and 18 months. In arteries isolated from DMO the relaxation induced by prostacyclin analogues was reduced in both 3- and 18-month old animals although endothelium (acetylcholine)-mediated relaxation was reduced in 18-month old DMO only.

Hyperoxia exposure impairs nephrogenesis in the neonatal rat: role of HIF-1α.

Preterm neonates are exposed at birth to high oxygen concentrations relative to the intrauterine environment. We have previously shown in a rat model that a hyperoxic insult results in a reduced nephron number in adulthood. Therefore, the aim of this study was to determine the effects of transient neonatal hyperoxia exposure on nephrogenesis.

Compensatory renal growth after unilateral or subtotal nephrectomy in the ovine fetus.

Background: Clinical and experimental studies show that unilateral (1/2Nx) and subtotal nephrectomy (5/6Nx) in adults result in compensatory renal growth without formation of new nephrons. During nephrogenesis, the response to renal mass reduction has not been fully investigated.

Methods: Ovine fetuses underwent 1/2Nx, 5/6Nx, or sham surgery (sham) at 70 d of gestation (term: 150 d), when nephrogenesis is active.

MMP9 limits apoptosis and stimulates branching morphogenesis during kidney development.

Early events in kidney organogenesis involve reciprocal interactions between the ureteric bud and the metanephric mesenchyme, which lead to remodeling of the extracellular matrix. This remodeling involves matrix metalloproteases (MMPs), but the specific roles of individual MMPs in kidney development are not completely understood. Here, we analyzed MMP9-deficient mice at the first step of kidney development and found that MMP9 deficiency delayed embryonic kidney maturation and increased apoptosis ex vivo by 2.

Early postnatal overfeeding induces early chronic renal dysfunction in adult male rats.

Low birth weight is associated with an increased risk of hypertension and renal dysfunction at adulthood. Such an association has been shown to involve a reduction of nephron endowment and to be enhanced by accelerated postnatal growth in humans. However, while low-birth-weight infants often undergo catch-up growth, little is known about the long-term vascular and renal effects of accelerated postnatal growth.

Neonatal oxygen exposure in rats leads to cardiovascular and renal alterations in adulthood.

Long-term vascular and renal consequences of neonatal oxidative injury are unknown. Using a rat model, we sought to investigate whether vascular function and blood pressure are altered in adult rats exposed to hyperoxic conditions as neonates. We also questioned whether neonatal O(2) injury causes long-term renal damage, important in the pathogenesis of hypertension.

Exposure to maternal diabetes induces salt-sensitive hypertension and impairs renal function in adult rat offspring.

Objective: Epidemiological and experimental studies have led to the hypothesis of fetal origin of adult diseases, suggesting that some adult diseases might be determined before birth by altered fetal development. We have previously demonstrated in the rat that in utero exposure to maternal diabetes impairs renal development leading to a reduction in nephron number. Little is known on the long-term consequences of in utero exposure to maternal diabetes.

Intra renal arterial injection of autologous mesenchymal stem cells in an ovine model in the postischemic kidney.

Background And Aims: Acute renal failure (ARF) remains a major healthcare problem. Although modern medical therapy has improved its outcome, the syndrome still has high mortality and morbidity rates [Xue et al.: J Am Soc Nephrol 2006;17:1135-1142].

Effects of early postnatal hypernutrition on nephron number and long-term renal function and structure in rats.

Various antenatal events impair nephrogenesis in humans as well as in several animal models. The consecutive low nephron endowment may contribute to an increased risk for cardiovascular and renal diseases in adulthood. However, little knowledge is available on the influence of the postnatal environment, especially nutrition, on nephrogenesis.

Kidney gene expression analysis in a rat model of intrauterine growth restriction reveals massive alterations of coagulation genes.

In this study, low birth weight was induced in rats by feeding the dams with a low-protein diet during pregnancy. Kidneys from the fetuses at the end of gestation were collected and showed a reduction in overall and relative weight, in parallel with other tissues (heart and liver). This reduction was associated with a reduction in nephrons number.

[Renal and urinary tract disease national research program].

The National Institute of Health and Medical Research (Inserm), the Society of Nephrology, and the French Kidney Foundation recognized the need to create a National Research Program for kidney and urinary tract diseases. They organized a conference gathering 80 researchers to discuss the state-of-the art and evaluate the strengths and weaknesses of kidney and urinary tract disease research in France, and to identify research priorities. From these priorities emerged 11 of common interest: 1) conducting epidemiologic studies; 2) conducting large multicenter cohorts of well-phenotyped patients with blood, urine and biopsy biobanks; 3) developing large scale approach: transcriptomics, proteomics, metabolomics; 4) developing human and animal functional imaging techniques; 5) strengthening the expertise in renal pathology and electrophysiology; 6) developing animal models of kidney injury; 7) identifying nontraumatic diagnostic and prognostic biomarkers; 8) increasing research on the fetal programming of adult kidney diseases; 9) encouraging translational research from bench to bedside and to population; 10) creating centers grouping basic and clinical research workforces with critical mass and adequate logistic support; 11) integrating and developing european research programs.

Expression of matrix metalloproteinases MMP-2 and MMP-9 is altered during nephrogenesis in fetuses from diabetic rats.

Remodeling of extracellular matrix (ECM) is an important physiological feature of normal growth and development. Recent studies have emphasized the role of matrix metalloproteinases (MMP-2 and MMP-9) in normal mouse nephrogenesis. We have demonstrated previously in the rat that in utero exposure to maternal diabetes impairs renal development leading to a 30% reduction in the nephron number.

High-frequency ultrasound detection and follow-up of Wilms' tumor in the mouse.

The goal of this study was to validate high-frequency (24 MHz) ultrasound imaging techniques for early detection and follow-up of renal tumors in a murine Wilms' tumor model (n = 26). For 11 mice, maximum tumor dimensions were estimated from images along three orthogonal axes for comparison with posteuthanasia caliper and histologic measurements. Tumor size in the 15 remaining mice was checked biweekly.

Identification of differentially expressed genes between fetal and adult mouse kidney: candidate gene in kidney development.

Background: The kidney development involves a wide variety of developmental processes requiring a lot of genes expressed in a sequential manner. The aim of the present study is to identify new genes involved in these processes.

Methods: To obtain a view of the mouse embryonic kidney transcriptome we used the SADE method, which allows large-scale quantitative gene expression measurements.

Effects of mild vitamin a deficiency on lung maturation in newborn rats: a morphometric and morphologic study.

Objective: To evaluate the effects of a 60% vitamin A deficiency (VAD) on the two postnatal stages of lung development: alveolarization and microvascular maturation. Lungs from deficient rats were compared to age-matched controls.

Study Design: Starting at 3 weeks before mating, female rats were maintained under a diet lacking vitamin A.

Midkine is involved in kidney development and in its regulation by retinoids.

In the kidney, in which development depends on epithelial-mesenchymal interactions, it has been shown that retinoids modulate nephrogenesis in a dose-dependent manner in vivo and in vitro. Midkine (MK) is a retinoic acid responsive gene for a heparin-binding growth factor. The aim of the present study was therefore to quantify the expression of MK mRNA during renal development in the rat, to analyze the regulation of MK expression by retinoids in vivo and in vitro, and, finally, to study the role of MK in rat metanephric organ cultures.