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19MEDICAL SCIENCES
THE INFLUENCE OF MOTHER'S EXTRAGENITAL PATHOLOGY ON THE FORMATION OF THYMUS OF THE PROCESSING IN THE EARLY POSTNATAL ONTOGENESIS
Azimova S.
Bukhara State Medical Institute, Department of Histology, Cytology and Embryology,
Bukhara, Uzbekistan
Abstract
The influence of extragenital pathology of the mother, on the example of chronic toxic hepatitis (CTG), on the development of the thymus of rat pups during the period of early postnatal ontogenesis was researched. It was found that against the background of mother's CTG, there is a decrease in the weight of rat pups 1 -7 days and a lag in growth by 7-21 days after birth and development of rat pups after birth, a decrease in both the absolute and relative mass of the thymus up to 21 days after birth. Morphologically, there is a violation of the formation of the thymus, manifested in the lag in the development of the structural and functional zones of the thymus, due to an increase in the area occupied by the connective tissue stroma, accompanied by the phenomena of hypoplasia.
Keywords: early postnatal ontogenesis, hepatitis, thymus development, rat pups.
The development and formation of the immune system in the pre- and postnatal periods of development depends on a number of factors, including the condition of health of the maternal organism, which may affect the morphogenesis of the fetal immune defense organs. A number of authors are of the opinion that changes in the functional condition of the mother's body during pregnancy, caused by infectious diseases, taking medications, can negatively affect the development of the immune system of the offspring [1,2,3,4,5,6]. Particularly, recently, among women of childbearing age, there has been an increase in extra genital diseases, including the hepatobiliary system. Particular interest are researches of the effect of chronic hepatitis in the mother during pregnancy, on the development of the immune system of the offspring at different periods of postnatal development, including the thymus - the central organ of immunity [7, 8, 9].
The thymus as the primary organ of the immune system largely determines not only the condition of the peripheral organs of immunogenesis, but also the severity of the protective reactions of the whole organism [10, 11]. Immunodeficiency condition in young children are quite common in clinical practice. Among the reasons leading to immunodeficiency, the predominant are unfavorable exogenous influences of various etiologies in the prenatal period of ontogenesis, as well as the presence of pathology of the maternal organism, not only in the prenatal period, but also during breastfeeding [12, 13, 14, 15]. At the same time, in the literature available to us, this issue remains poorly understood.
The aim of our research was to study the mother's chronic heliotrinic hepatitis on the development of the thymus of the offspring in the period of early postnatal ontogenesis.
Material and methods
The experiments were carried out on 50 sexually mature female white outbred rats weighing 130-150 g. All animals were quarantined for two weeks to exclude infectious diseases. Animals were divided into 2 groups (50 rats in each): experimental and control. A model of
heliotrinic hepatitis was prepared by weekly administration of 0.05 mg of heliotrin per gram of body weight for 6 weeks. The control group of animals received sterile saline instead of heliotrin. 10 days after the last injection, males were added to the females. In the future, the course of pregnancy was monitored. It should be noted that the experiments were carried out in accordance with the requirements of the "European Convention for the Protection of Vertebrate Animals Used for Experimental and Scientific Purposes" and the principles of the Declaration of Helsinki on the humane treatment of animals. The pups were decapitated under light ether anesthesia on the 1st, 3rd, 7th, 15th, 21st and 30th days after birth. Pieces of thymus, fixed in 12% neutral formalin or Bouin's liquid, were embedded in paraffin after appropriate wiring. Sections 5-7 ^m thick were stained with hematoxylin and eosin and used for morphological and morphometric researches. Morpho-metric researches were carried out using the Avtandilov grid per unit area according to the generally accepted method. Statistical processing of the data obtained was carried out using computer programs.
Results and discussion
Consequently to our morphological researches, it was found that in newborn rat pups (intact and control group) the thymus is sufficiently formed and consisted of two lobes. Outside, the thymus was covered with a capsule, from which connective tissue septa departed, dividing the lobes into lobules. The lobules are characterized by a clear differentiation into cortical and medullary substance, a high density of distribution of cells in the cortex of the thymic lobule rather than in the medulla. The cortex was mainly represented by lymphocytes and accounted for two-thirds, in the medulla, the medulla consisted mainly of reticuloepithelial cells and corresponded to one-third of the lobule. The location of lymphoblasts is noted mainly in the subcapsular space of the cortex; in some cases, a narrow epithelial space was found under the capsule in rats. In addition, mitot-ically dividing lymphocytes and a large number of medium and small lymphocytes were more often found in the cortex of the thymic lobules.
Note: 1. conditional abbreviations - group of animals, K - control, E-experienced;
2. the values where the differences are significant are highlighted in bold relative to the previous
period at P <0.05.
Table 2.
Influence of toxic maternal hepatitis on the development of structural and functional zones of the thymus of rat pups in the dynamics of early postnatal ontogenesis (X ± Sx)
The brain substance of the thymus of newborn rat pups was characterized by a reduced number of lymphocytes, between which were located both individual reticular epithelial cells with increased oxyphilia of the cytoplasm, macrophages and monocyte-like cells, and Gassal's thymic bodies.
As a result of our research, against the background of chronic hepatitis of the mother, not only a peculiar dynamics of morphological changes in the thymus of
Table 1.
Influence of toxic maternal hepatitis on some anthropometric parameters and thymus mass in rat pups in the dy-
the offspring is revealed, but also, as the results of our research have shown, chronic toxic hepatitis of the mother contributes to the growth retardation in the offspring, expressed in a decrease in body weight by 1 -3 days after birth and body lengths of animals, marked 714 days after birth. In addition, a decrease in the mass of the thymus of rat pups was established up to 21 days of development (see Table 1).
Morphometric A group of animals Age of animals (in days)
indicators of the thymus 1 3 7 15 21 30
C 5,6± 6,0± 8,9± 18,6± 29,1± 42,3±
Rat weight, g 0,08 0,09 0,11 0,43 0,82 0,75
E 5,1± 5,3± 8,1± 16,9± 26,8± 34,7±
0,11 0,13 0,12 0,42 0,55 1,14
C 27,1± 33,0± 44,2± 51,6± 55,2± 57,6±
Rat body length, mm 0,47 0,58 0,39 0,52 0,88 0,96
E 23,9± 27,1± 36,4± 41,5± 47,6± 51,6±
0,43 0,52 0,48 0,52 0,82 1,05
C 10,1± 18,1± 26,4± 78,5± 133,0± 221,0±
Absolute weight of 0,20 0,38 0,72 3,42 6,62 4,57
the thymus, g E 8,3± 16,0± 22,9± 71,9± 119,6± 181,6±
0,36 0,45 0,69 3,12 4,13 4,25
C 0,18± 0,26± 0,19± 0,48± 0,60± 0,52±
Relative weight of the 0,012 0,008 0,005 0,023 0,013 0,014
thymus (x10-2) E 0,17± 0,32± 0,26± 0,37± 0,47± 0,53±
0,006 0,012 0,009 0,019 0,014 0,017
Day of postnatal development A group of animals Thymus zones Connective tissue stroma
Cork Brain
rel. units % rel. units % rel. units %
1 day C 476,8±23,2 74,5 151,6±9,6 23,6 11,6±0,12 1,9
E 496,6±18,9 77,5 129,3±8,4 20,3 14,1±0,15 2,2
3 days C 475,5±21,1 74,3 151,7±10,3 23,7 12,8±0,21 2,0
E 488,8±19,7 76,4 136,5±8,1 21,3 14,7±0,31 2,3
7 days C 446,7±21,6 69,8 180,5±9,2 24,9 12,8±0,21 2,0
E 483,2±22,8 75,5 141,4±10,2 22,1 15,4±0,34 2,4
14 days C 457,6±20,6 71,5 168,3±11,7 26,3 14,1±0,32 2,2
E 469,8±32,7 73,4 155,5±13,6 24,3 14,7±0,38 2,3
21 days C 451,8±41,6 70,6 171,6±15,8 26,8 16,6±0,34 2,6
E 453,2±30,8 69,1 168,6±13,5 27,9 17,2±0,41 3,0
30 days C 455,0±38,5 71,1 165,8±16,3 25,9 19,2±0,65 3,0
E 460,2±35,6 71,9 159,3±15,3 24,6 20,5±0,82 3,2
The thymus of newborn rats, an experimental group of animals that developed against the background of toxic maternal hepatitis, is characterized by pronounced structural changes in the processes of differentiation of the thymus into cortical and medulla, in favor of the cortical, which is quite clearly expressed in newborn rat pups. At the same time, it should be noted that the density of distribution of cells in the cortex is markedly reduced. There is a significant decrease in the
number of lymphoblasts (by 15%), small lymphocytes (by 20%). The continuation of this trend was characteristic for the subsequent periods of postnatal thymus development. Attention is drawn to the increase in the number of destructive thymocytes, which at various times after birth exceeded the parameters of the control group by 2-3 times. Along with this, large macrophages with dense inclusions in the cytoplasm, apparently also a sign of increased thymocytolysis, were encountered
on the thymus sections of the experimental group much more often than in the control group. The severity of the described changes decreased only by the 30th day of postnatal ontogenesis. Conducted morphometric researches made it possible to establish, only an increase in the area occupied by connective tissue for 1-7 days after delivery (see Table 2)
Thereby, with CTG of the mother, the development of the offspring has a negative effect, expressed in a decrease in the weight of rat pups by 1 -3 days and a growth retardation is most pronounced at 7-14 after birth, there is also a decrease in the weight of the thymus up to 21 days of development. Morphologically, in the thymus of offspring born from female rats with chronic heliotrinic hepatitis, in the dynamics of early postnatal ontogenesis, hypoplasia and a lag in the development of structural and functional zones of the organ are noted, due to an increase in the area occupied by the connective tissue stroma.
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