ИСТИНА

Background: The study of prenatal hypoxic stress at different stages of embryonic development attracts great attention of physiologists and clinicians in connection with various pathological conditions in the postnatal period, as well as in connection with the search for drugs that reduce or eliminate the observed disorders. In aim of this paper was to perform a comparative analysis of acute hypobaric hypoxia effects on the 4/5th, 9/10th and 20/21st day of pregnancy on the development in the early postnatal period according to morphometric parameters, anxiety level, locomotor and research activity in rat pups. The age of the 22nd day of life was chosen for behavioral activity analysis because this age is known as one of the key stages of early ontogenesis, when a number of physiological functions become established and a transition to self-feeding begins. Methods: The work was performed on male and female Wistar rats. Pregnant females were subjected to acute hypobaric hypoxia in one of the critical stages of embryonic development: (1) pre-implantation (4/5th day); (2) early organogenesis (9/10th day); (3) prenatal period (20/21st day). The body weight and growth were monitored for three weeks after birth in newborns survived hypoxia in utero. The behavioral activity and anxiety level were evaluated in 22-day-old rat pups using “Hole board” and “Elevated X-maze” tests. Statistical analysis was performed using Statistica 10.0 (StatSoft Inc., Tulsa, USA. Experimental groups were compared using non-parametric Mann–Whitney U-test. Correlation analysis was performed using Spearman rank correlation coefficient. Differences with p ≤ 0.05 were considered significant. Results: The adverse pregnancy outcomes were more often observed in females subjected to acute hypobaric hypoxia in early organogenesis and prenatal periods (20% and 30% above corresponding control group, respectively). Rat pups survived intrauterine stress during early organogenesis were born with a backlog in physical development, which persisted throughout the observation period while kittens survived prenatal hypoxia were born with normal body weight, but began to lag behind in physical development from the 8th day of life. The comparative analysis of locomotor and research activity, as well as the anxiety level revealed that the period of early organogenesis and prenatal period were also more sensitive to the effects of the hypoxic stress. Behavior deviations following acute hypoxia in early organogenesis were characterized by a disturbance in anxiety and risk behavior balance, whereas after prenatal hypoxia the decrease in locomotor and research activity were also registered. The correlation analysis did not reveal the relationship between the lag in physical development and the reduction of motor activity, as well as with other behavioral parameters. Thus the disturbances observed in newborns can not be explained only by their reduced body weight, but most likely are caused by pathological dysfunctions affecting central nervous system.Conclusion. Data obtained allow to come to a conclusion that acute hypoxia in early organogenesis and prenatal periods has more pronounced consequences in the early postnatal period than hypoxia in the pre-implantation period.