Structural/Functional Modifications in the Mitochondria of Brainstem Cells in Rat Offspring Subjected to Prenatal Hypoxia

Abstract

We examined changes in the morphofunctional state of the mitochondria (MCh) and immunohistochemical peculiarities of brainstem neurons in rat offspring exposed to experimental prenatal (intrauterine) hypoxia of different severity, moderate and strong. This was provided by exposure of pregnant females to O2/N2 respiratory mixtures containing 12 and 7% O2, respectively. Experimental groups included 20 one-month-old rats (offspring of 9 females, control and subjected to hypoxia). We estimated the ultrastructural characteristics of the MCh and also expression of the CD95 APO-1/Fas and Bcl-2 genes modulating the intensity of apoptosis and mitoptosis in these cells. Severe intrauterine hypoxia resulted in the development of structural distress in the MCh of brainstem cells; all stages of MCh degradation, from swelling to complete dissipation, were observed. Juvenile forms of these organelles were absent. Mosaic-like destruction of myelin with manifestations of edema was observed. After the moderate prenatal hypoxia, about half of the changes in the MCh ultrastructure could be qualified as directed toward an increase in the compensatory capabilities of the MCh apparatus. In rats after moderate hypoxic influence, levels of expression of the CD95 APO-1/Fas and Bcl-2 genes were indicative of a greater readiness of the neurons to apoptosis and decrease in the probability to inhibition of the respective MCh pathway in brainstem neurocites. At the same time, the MCh and neurocites of animals subjected to severe intrauterine hypoxia demonstrated decreased trends toward mitoptosis and apoptosis, respectively. The obtained results characterizing the effects of intrauterine hypoxia of different levels on the formation of structural/functional changes in the MCh of brainstem cells can be taken into account in the process of development of novel approaches to the treatment of MCh diseases.