THE EFFECT OF DIFFERENT TYPES OF HYPOXIA ON THE MORPHO-FUNCTIONAL STATE OF THE KIDNEYS OF FETUSES AND NEWBORNS: THE RESULTS OF OWN LONG-TERM EXPERIMENTAL STUDIES: THE EFFECT OF DIFFERENT TYPES OF HYPOXIA ON THE MORPHO-FUNCTIONAL STATE OF THE KIDNEYS OF FETUSES AND NEWBORNS

Abstract

Introduction. The vast majority of kidney diseases in children and adults have their origins in the antenatal, intranatal or postnatal periods of development. Poor health of women of childbearing potential, complications during pregnancy and delivery often lead to the development of various types of hypoxia (chronic intrauterine hypoxia (CIH), acute intranatal hypoxia, acute postnatal hypoxia (APH), mixed hypoxia (MH)). The latter are a common cause of fetal and neonatal disorders, leading to damage of various organs and systems, including the kidneys. The purpose is to highlight the main results of own long-term experimental studies aimed at determining the effect of different types of hypoxia (CIH, APH, MH) on the morpho-functional state of the kidneys in fetuses and newborns. Materials and methods. In this study, the author modelled alpine hypoxia using a sealed pressure chamber from which air was pumped out, creating conditions for a sharp decrease in atmospheric pressure. Every day, we placed mature female rats with an average weight of 220–250 g in conditions corresponding to 7,500 meters hight at 287 mm Hg for 20 minutes at the same time. During the experiment, we ranked the animals into four groups: group 1 – control group – pregnant female rats (n=3) that did not experience alpine hypoxia, some females were removed from the experiment in late gestation to remove fetuses (n=7). The offsprings (n=11) received from the rest of the females, were removed from the experiment on the first day after birth. Group 2 – a study group with simulation of CIH – pregnant female rats (n=4) throughout pregnancy (21 days) were subjected to daily alpine hypoxia, with some females removed from the experiment in late gestation to remove fetuses (n=6). Offsprings (n=10) from the rest of the females were removed from the experiment on the first days of life. Group 3 – a study group with modeling of APH – pregnant female rats (n=2) were not subjected to alpine hypoxia, but their offsprings (n=8) on the first day of life were subjected to alpine hypoxia once for 15 minutes, and then they were removed from the experiment. Group 4 – a study group for modeling MH – pregnant female rats (n=3) throughout pregnancy were subjected to daily alpine hypoxia, then the offsprings obtained from them (n=8) on the first day of life were subjected to alpine hypoxia once for 15 minutes and removed from the experiment. Histological, histochemical, immunohistochemical, morphometric and statistical research method were used. Results. Acute postnatal, chronic intrauterine and mixed hypoxia lead to the development of respectively minimal, moderate and pronounced morphological changes in the capsules, parenchymal and stromal-vascular components of the kidneys, primarily damaging the vessels of the stroma and parenchyma, where more pronounced changes occur in the tubules, collecting tubules, and in chronic intrauterine hypoxia these changes increase in newborns compared to fetuses. Experimental hypoxia causes the development of hemodynamic disorders, degenerative-desquamative changes of vascular endotheliocytes, epitheliocytes of Bowman's capsules, tubules, collecting tubules, and the latter in acute postnatal hypoxia are observed mainly in the proximal tubules, and in chronic intrauterine and mixed hypoxia in all parts of the tubular system and collecting tubules. Chronic intrauterine and mixed hypoxia promote cyst formation, delay the processes of glomerulogenesis and tubulogenesis. Acute postnatal, chronic intrauterine and mixed hypoxia stimulate fibroblastic cells in the kidneys, and chronic intrauterine and mixed hypoxia also induce epithelial-mesenchymal transformation, causing the development of sclerosis. Acute postnatal, chronic intrauterine and mixed hypoxia induce apoptosis, proliferation, leading to an imbalance between them due to the prevaling proliferation in acute postnatal and chronic intrauterine hypoxia and apoptosis in mixed hypoxia. Conclusions. Identified morphological changes in the kidneys of fetuses and newborns developed under the influence of acute postnatal, chronic intrauterine and mixed hypoxia, given the unity of structure and function, will lead to functional changes in these organs in subsequent postnatal ontogenesis in such children and the emergence of different nephrological pathology. This study actualizes the implementation of preventive measures among persons of reproductive age, dictates the need for quality pre-pregnancy training, which should be aimed at timely detection and treatment of genital and extragenital pathology in women. Keywords: acute postnatal hypoxia, chronic intrauterine hypoxia, fetus, kidneys, mixed hypoxia, morphology, newborn.