Altered ureteric branching morphogenesis and nephron endowment in offspring of diabetic and insulin-treated pregnancy

<div><p>There is strong evidence from human and animal models that exposure to maternal hyperglycemia during <i>in utero</i> development can detrimentally affect fetal kidney development. Notwithstanding this knowledge, the precise effects of diabetic pregnancy on the key processes of kidney development are unclear due to a paucity of studies and limitations in previously used methodologies. The purpose of the present study was to elucidate the effects of hyperglycemia on ureteric branching morphogenesis and nephrogenesis using unbiased techniques. Diabetes was induced in pregnant C57Bl/6J mice using multiple doses of streptozotocin (STZ) on embryonic days (E) 6.5-8.5. Branching morphogenesis was quantified <i>ex vivo</i> using Optical Projection Tomography, and nephrons were counted using unbiased stereology. Maternal hyperglycemia was recognised from E12.5. At E14.5, offspring of diabetic mice demonstrated fetal growth restriction and a marked deficit in ureteric tip number (control 283.7±23.3 vs. STZ 153.2±24.6, mean±SEM, <i>p</i>&lt;0.01) and ureteric tree length (control 33.1±2.6 mm vs. STZ 17.6±2.7 mm, <i>p</i> = 0.001) vs. controls. At E18.5, fetal growth restriction was still present in offspring of STZ dams and a deficit in nephron endowment was observed (control 1246.2±64.9 vs. STZ 822.4±74.0, <i>p&lt;</i>0.001). Kidney malformations in the form of duplex ureter and hydroureter were a common observation (26%) in embryos of diabetic pregnancy compared with controls (0%). Maternal insulin treatment from E13.5 normalised maternal glycaemia but did not normalise fetal weight nor prevent the nephron deficit. The detrimental effect of hyperglycemia on ureteric branching morphogenesis and, in turn, nephron endowment in the growth-restricted fetus highlights the importance of glycemic control in early gestation and during the initial stages of renal development.</p> </div

Ouabain protects against adverse developmental programming of the kidney

The kidney is extraordinarily sensitive to adverse fetal programming. Malnutrition, the most common form of developmental challenge, retards the formation of functional units, the nephrons. The resulting low nephron endowment increases susceptibility to renal injury and disease. Using explanted rat embryonic kidneys, we found that ouabain, the Na,K-ATPase ligand, triggers a calcium–nuclear factor-κB signal, which protects kidney development from adverse effects of malnutrition. To mimic malnutrition, kidneys were serum deprived for 24 h. This resulted in severe retardation of nephron formation and a robust increase in apoptosis. In ouabain-exposed kidneys, no adverse effects of serum deprivation were observed. Proof of principle that ouabain rescues development of embryonic kidneys exposed to malnutrition was obtained from studies on pregnant rats given a low-protein diet and treated with ouabain or vehicle throughout pregnancy. Thus, we have identified a survival signal and a feasible therapeutic tool to prevent adverse programming of kidney development

Novel (bio)chemical and (photo)physical probes for imaging live cells

Emerging technologies, utilizing a combination of chemistry, physics and molecular biology, are creating an increasing interest in smart materials serving as reporters and sensors in micro- and nano-systems. Such devices constitute unique tools for a plethora of biological applications and therapies, allowing in vivo and real time monitoring of biomolecular structure and function. Imaging live cells poses a number of problems, not the least of which is to minimize the perturbation of the physiological state and viability of the cells with the probes and "tools". One seeks to achieve single molecule sensitivity (when appropriate and desirable), monitor fast kinetic processes, and observe molecular interactions occurring on distance scales far beyond the optical resolution of light microscopes. In the remainder of this contribution we discuss a few methods that have already attained some of these goals and present some model systems that hold the promise for achieving others. (excerpt from Section 2, this article contains no abstract

Novel (bio)chemical and (photo)physical probes for imaging live cells

Emerging technologies, utilizing a combination of chemistry, physics and molecular biology, are creating an increasing interest in smart materials serving as reporters and sensors in micro- and nano-systems. Such devices constitute unique tools for a plethora of biological applications and therapies, allowing in vivo and real time monitoring of biomolecular structure and function. Imaging live cells poses a number of problems, not the least of which is to minimize the perturbation of the physiological state and viability of the cells with the probes and "tools". One seeks to achieve single molecule sensitivity (when appropriate and desirable), monitor fast kinetic processes, and observe molecular interactions occurring on distance scales far beyond the optical resolution of light microscopes. In the remainder of this contribution we discuss a few methods that have already attained some of these goals and present some model systems that hold the promise for achieving others. (excerpt from Section 2, this article contains no abstract