Rom J Leg Med [22] 199-208 [2014] DOI: 10.4323/rjlm.2014.199 © 2014 Romanian Society of Legal Medicine The significance of reciprocal induction relations between the derivates of nephrogenic mesoderm. Implications in pathology and regeneration Gheorghe S. Dragoi1,*, Petru Razvan Melinte2, Ileana Dinca2, Elena Patrascu2, Serban A. Dragoi3 _________________________________________________________________________________________ Abstract: Functional capacity of renal excretory biosystem is assured by remarkable complex structures: glomerular basal membrane for ultrafiltration of blood plasma, tubular system of the nephron for resorption-secretion processes and juxtaglomerular complex for self-balancing.The purpose of the paper is to draw the attention of histopathologists over the phenotypic transformation of metanephrogen mesenchyme and over the relations between derivates of this mesenchyme in the ontogenesis process, with implications in pathology and regeneration. Authors conducted this study and, by classical microanatomic methods, they highlighted the structural heterogeneity of renal cortex, the phenotypic variability of glomerular capillary network, the spatial distribution and the relations of intraglomerular mesangial matrix Based on personal observations, authors notice the fact that only a proper acknowledgement of reciprocal induction relations consequences between ureteric bud emerged from mesonephros and metanephrogenic blastema allows the understanding of renal parenchyma structural particularities and the determinant factors in anatomical-functional disposition of renal excretory biosystem, as well as the implications in pathology and regeneration. Key Words: nephron, renal glomerulus, metanephrogenic mesenchyme, ureteric bud, reciprocal induction, kidney stem cells. he functional structures of renal excretory nephrogenic mesoderm? system are determined during ontogenesis by What are the determining factors for the competence T the phenotype changes of metanephrogen mesenchyme, of metanephrogenic mesenchyme to specifically respond to the in the presence of reciprocal induction relations between inductive action of ureteral bud derived from mesonephros the derivates of nephrogenic mesoderm (Mesoderma mesenchyme? intermedium). The structural heterogeneity of renal What are the topographic, anatomic and functional parenchyma and the phenotype variability of its elements relations between the derivates of metanephrogenic raised many problems regarding their genesis and evolution: mesenchyme? How is achieved the formation of many structural What are the necessary and sufficient conditions elements of renal parenchyma from the mesenchyme of for the phenotype differentiation of the elements of nephrogenic mesoderm that is initially a homogenous metanephrogenic mesenchyme into the endothelial, epithelial structure?; and mesangial structures? Is it possible that the elements of renal parenchyma Are there any stem cells present inside completely have another origin beside primordial mesenchyme of differentiated renal parenchyma and what is their location? 1) Romanian Academy of Medical Sciences, Bucharest, Romania * Corresponding author: Prof.MD, PhD, E-mail [email protected] 2) University of Medicine and Pharmacy of Craiova, Department of Anatomy, Craiova, Romania 3) Division of Nephrology and Hypertension, Georgetown University, Washington DC, 20007,USA 199 Dragoi G.S. et al The significance of reciprocal induction relations between the derivates of nephrogenic mesoderm Is there a genetic control over the phenotype changes walls of the capsular space belong to proximal convoluted undergone by metanephrogenic mesenchyme? tube derived from metanephrogenic mesenchyme after What is the practical importance for the knowledge tubule-genesis processes. The glomerular capillary network of relations between the derivates of metanephrogenic is also derived from metanephrogenic mesenchyme after mesenchyme in pathomorphgenesis and/or in nosologic vasculogenesis processes, offering a structural autonomy classification of elementary renal lesions? to renal glomerulus. Between the two derivates from We proposed ourselves to perform a microanatomic metanephrogenic mesenchyme establish contiguity relations analysis of the relations between the derivates of after the adhesion of internal wall of capsular space to the metanephrogenic mesenchyme, that is necessary for the glomerular arterial capillaries network. Thus, the anatomic rigorous evaluation in optic microscopy of the structures and functional unit of glomerular filtration is formed; it is involved in filtration, resorption and secretion inside known as basal glomerular membrane (membrana basalis) renal excretory system. The purpose of the paper is to that also includes intraglomerular mesangium. draw the attention on the phenotype changes undergone d. Mesangium forms a glomerular stroma and is by metanephrogenic mesenchyme and on the relations a supportive structure for glomerular arterial capillaries. between the derivate of this mesenchyme during ontogenesis In the structure of mesangium we find mesangial dynamics; we also deal with their implications in pathology cells (Mesangiocytus) and a mesangial matrix (Matrix and regeneration processes. mesangialis) that play important roles in the regulation of Problems raised by semantic content and use of blood flow and glomerular filtration. terms in the structural anatomy of renal parenchyma. There e. Nephrogenic mesoderm, known as mesoderma are numerous difficulties in understanding the anatomic intermedium, contains mesenchyme that will form the descriptions in some books, due to the confusing semantic nephrogenic chord that will metameric segment and content of terms or their wrong use while nominating achieve two ephemeral structures in the superior and different structures. The international homologation of middle parts of embryo: pronephros and mesonephros. At the terms used in the description of renal parenchyma the caudal part of embryo, still remains a non-segmented was achieved on the following organization levels: macro- sector from the nephrogenic chord – metanephros. anatomic, micro-anatomic and embryologic. The terms that By metanephrogenic bud (Massa metanephrogenica, nominate anatomic structures involved in time and space Metanephrogenic blastema), metanephros will contribute to progress of renal functions such as filtration, resorption the formation of definitive kidney after reciprocal induction and secretion, still need to the emphasized: nephronum, to ureteral bud (Diverticulum metanephricum) developed corpusculum renale, glomerulus, mesangium, mesoderma from Wolff canal [6]. The absence of ureteral bud lead to intermedium, mesonephros, metanephros, induction, the non-differentiation of metanephrogenic blastemal and vasculogenesis. consequently to renal agenesis. a. Nephron (Nephronum) is an anatomic and f. Induction is a process involved in organogenesis; functional system made of renal corpuscle (corpusculum an embryonic region interacts with another region in order to renale) and tubular subsystem (tubulus renalis). The influence its differentiation or behavior. There are two types collecting duct (ductus colligen) and papillary duct (Ductus of induction: 1. Primary embryonic induction that is at the papillaris) are not parts of nephron Histologic Terminology basis of the formation of embryo dorsal axis; 2. Secondary (2008) incorporate them [1]. induction – a group of cells respond to the action of another b. Renal corpuscle (Corpusculum renale) is a group of cells (example: epithelium-mesenchyme); it has a subsystem of nephron, made of renal glomerulus discovered regional and genetic specificity. by Malpighi (1666) [2] and glomerular capsule (capsula g. Vasculogenesis is the process of blood vessel glomerularis) described by Bowman (1842) [3]. formation that take place by the production “de novo” c. Renal glomerulus (glomerulus) is the structural of endothelial cells. It takes place during the embryonic unit of renal corpuscle and it is made of arterial blood development of blood vessels and during tumor growing capillaries (Vas capillare glomerulare) that form the in adults. Another process of blood vessels formation is glomerular capillary network (Rete capillare glomerulare) angiogenesis that is different from vasculogenesis and and intraglomerular mesangium located in the spaces consists of the burgeoning of preexistent vessels. between capillaries. The term of renal glomerulus is frequently used as a synonym to renal corpuscle. But MATERIALS AND METHODS facts related to vasculogenesis and tubule-genesis plead against it. Because of the contiguity relations that establish The microanatomic study of the effects generated between the metanephrogenic mesenchyme derivates by reciprocal induction processes between the structures – glomerular arterial capillaries network and proximal of nephrogenic mesoderm, was achieved on fragments of convoluted tube – there is a capsular space (Spatium kidney harvested from three seven months old fetuses, from capsulare; Spatium urinarium) limited by an external wall adults aged 25 and 35 years old and from three embryos aged made of epithelial cells (Epitheliocytus parietalis) and an 8 weeks old. The fragments were fixed in 8% formaldehyde internal wall made of capsular visceral cells (Podocytus; solution buffered at pH 7.2 and then embedded in paraffin Visceral cell of capsule). One can easily notice that the using classical methods. 5 microns serried sections were