Prenatal Ontogenesis Research Articles

ENZYMES AND METABOLITES OF ENDOGENOUS CARBON MONOXIDE IN THE FETOPLACENTAL SYSTEM DURING PHYSIOLOGICAL GESTATION AND PLACENTAL DYSFUNCTION

Introduction. Prenatal ontogenesis largely depends on the functional and metabolic viability of the placenta and the entire fetoplacental complex. That is why the dysfunction of the placenta due to the changes in cellular regulation processes will lead to pregnancy complications and impaired fetal develop-ment. An important component of the system of intra- and intercellular regulators is the gas transmitter – carbon monoxide. Its role in cellular signaling and communication reactions, and at the same time, insufficient data of its metabolism, justifies the need to conduct research on this gas transmitter during complicated pregnancy. The aim of the work. To study the features of the metabolism of the active cellular mediator - the gas transmitter carbon monoxide in different objects of the fetoplacental system during physiological pregnancy and placental dysfunction. Material and methods. The research materials included placental tissue, amnion and amniotic fluid. The work uses spectrophotometric methods, enzyme immunoassay, and ion exchange chromatography. Results. Multidirectional changes in the activity of the studied enzymes (heme oxygenase and histidine decarboxylase), the content of the substrate of His-tidine reaction and the product of reaction of Histamine are established in case of placental disfunction. There is a certain correlation between the discov-ered studied components. Indicators of carbon monoxide metabolism can be markers for predicting postnatal damage – cerebral disorders in newborns. Conclusions. The identified injuries are obviously important links in the chain of disorders accompanied by the development of placental dysfunction.

Morphological methods in the study of the anatomy and topography of the human pelvic organs and structures in the fetal period of ontogenesis

Aim to identify the features of the use of various morphological methods, their informative value, advantages and disadvantages in studying the topographic anatomy of organs and structures of the fetal pelvis of the fetus. Material and methods. The study was carried out on the material of 100 human fetuses of both sexes using classical morphological methods (macromicropreparation, the method of cutting according to N.I. Pirogov, histotopographic method). Results. Macromicroscopic dissection in the study of pelvic organs in prenatal ontogenesis makes it possible to determine the position of organs and structures, their course and direction, symmetry with respect to paired organs. Dissection makes it possible to identify vascular and nerve structures, which is necessary when interpreting data obtained using other methods. Dissection does not allow to determine the skeletotopy of the organs and structures of the pelvis, their relative position relative to each other and bone structures, the relationship with the walls of the pelvic cavity. The use of the method of cutting according to N.I. Pirogov and the histotopographic method made it possible to describe of all horizontal sections from the LIII level to the subcutaneous floor of the perineum, as well as clinically important sagittal and frontal sections, was given. These methods allow us to define the skeletotopy of the organ, its relationship with the walls of the pelvic cavity, to study the ratio of the volume of the occupied organ in the cavity, as well as measure distances. The histotopographic method makes it possible to study in detail the internal structure, microtopography of organs and neurovascular complexes of the pelvis. This is the most informative method when studying the perineum. The article presents photographs of preparations demonstrating the features of the topographic anatomy of the fetal pelvis. Conclusions. It is possible to study in detail the topographic anatomy of the fetal pelvis, as well as to give a detailed description of the skeletotopy and syntopy of each organ only when using the complex of morphological methods presented. Using this approach, the data obtained will be useful to specialists of prenatal diagnostics, as well as during fetal operations.

Anatomical and topographic patterns of the thymus of black-and-white calves in prenatal ontogenesis

The thymus is the main organ of the immune system, which is responsible for the formation and maintenance of immunogenesis, as well as the proliferation and differentiation of T-lymphocytes. In embryogenesis, the growth and development of the thymus occurs earlier than other peripheral organs of the immune system. Its laying in cattle is carried out in the early period of embryonic development (25-27 days), according to the periodization of life and critical phases of ontogenesis. By the time of birth, the thymus is fully formed and functional. Due to the successful development of immunology, information about the morphofunctional patterns of the organs of the immune system is significantly supplemented. However, despite significant advances in this field of morphology and physiology of immunocompetent organs, many questions, in particular about the structure of the thymus, remain insufficiently studied, especially in productive animals of different species and breeds. The study was conducted at the Department of Animal Anatomy of the St. Petersburg State University of Veterinary Medicine. The material was the corpses of the fruits of black-and-white calves in the amount of seven pieces at the age of 8-9 months of intrauterine development, with an average weight of 20.0 kg. Fine anatomical dissection, morphometry, weighing, and photographing were used as research methods. The aim of the study was to establish anatomical and topographic patterns of the thymus of black– and-white calves in prenatal ontogenesis, as well as to obtain morphometric data. As a result of the study, it was found that the thymus topographically begins from the thirteenth tracheal ring and goes to the third rib and consists of three lobes: cervical, middle, thoracic. The cervical lobe prevails over the middle and thoracic in all linear parameters, except for the width of the thoracic lobe. The intensity of growth of the cervical and thoracic lobes is asynchronous.

ONTOGENETIC TRANSFORMATIONS OF BONES OF THE HUMAN ORBIT

Introduction. Elucidation of the sources of human orbital bones, clarifi cation of the sequence of their ossifi cation will allow to create a morphological basis for eff ective interpretation of the data of fetal condition monitoring, will contribute to early diagnosis of variants of the structure and possible malformations of the head, organ of vision and related structures.The aim of the study. The aim of this work was to fi nd out the sources of origin, the chronology of ossifi cation, the characteristics of age-related topographic and anatomical changes in the bones of the orbit.Material and methods. 18 series of histological sections of samples of human embryos and pre-fetuses at the age of 4-12 weeks of intrauterine development (4,0-80,0 mm parietal- coccygeal length) and samples of 12 fetuses at the age of 4-9 months of intrauterine development (130,0-450. 0 mm parietal- calcaneal length) using a complex of morphological research methods (anthropometry, morphometry, preparation of histological sections, dissection, three- dimensional reconstruction of series of histological sections and computer tomography, statistical analysis).The study was conducted in accordance with the main provisions of the European Union Convention on Human Rights andBiomedicine (1997), as well as the Helsinki Declaration on Ethical Principles of Medical Research Involving Human Subjects(1964-2008), EU Directive No. 609 (1986), Order of the Ministry of Health of Ukraine dated 23.09.2009 No. 690.The work was carried out within the framework of the initiative research work of the Department of Histology, Cytology andEmbryology of the Bukovinian State Medical University «Structural and functional peculiarities of tissues and organs in ontogenesis, regularities of variant, constitutional, sex and age-related and comparative human morphology». State registration number: 0121U110121. Deadlines: 01.2021-12.2025.The results. The fi rst signs of the appearance of ossifi cation centers around the main nervous and visceral contents of the rudiment of the orbit are determined in 6-week-old embryos in the form of seven cartilaginous bone models, and the fi rst centers of ossifi cation among the rudiments of bones participating in the formation of the orbit are found in the rudiment of the maxilla. In the 6th month of intrauterine development, the processes of ossifi cation of the frontal, sphenoid, ethmoid and maxillary bones begin. At the end of the 8th month of intrauterine development, due to the ossifi cation processes of the lesser wing of the sphenoid and frontal bones, the orbit acquires features of a defi nitive structure.From the beginning of the fetal period of human ontogenesis, ossifi cation of the structures of the sphenoid bone continues, which leads to morphological transformations of the orbit in 5-month fetuses – it is separated from the sphenopalatine and infratemporal fossa by a bone layer, the optic canal is formed, and in 6-month fetuses processes of ossifi cation of the frontal, sphenoid, ethmoid and maxillary bones, and Müller’s orbital muscle changes its structure into a fi brous one.The analysis of the age-related dynamics of the morphometric parameters of the orbit during the fetal period of intrauterine development made it possible to establish the peculiarities of changes in its diameter, circumference and area, which are expressed by mathematical functions: diameter of the orbit, mm = –0. 2285+0.4704*x; circumference of the orbit, mm = –0.2924+1.4595*x; area of the orbit, mm2 = –87.8597+8.0387*x, where x is the age of the human fetus in weeks.Conclusion. The critical periods of the development of the orbit are the 6th month of prenatal ontogenesis, during which there is an uneven growth rate of the horizontal size of the orbit in relation to the vertical one, and its shape returns to the mesoconchal, which was previously observed in fetuses, as well as the 8th month, during which the growth of all parameters of the orbit slows down due to intensive processes of organogenesis of its visceral structures.

Intracellular rearrangements of the rat contractile myocardial apparatus during prenatal ontogenesis after alcohol influence

Background. Information on the formation of the contractile apparatus of the heart and the distribution of myofibrils in cardiomyocytes under conditions of intrauterine intoxication with ethanol remain a subject of considerable debate. The aim of the study was to determine changes in the ultrastructure of the contractile apparatus of rat ventricular cardiomyocytes during prenatal development in conditions of intrauterine alcohol intoxication. Methods. The object of the research was the hearts of rat posterity at different times from birth to adulthood in the model of chronic alcohol intoxication of the maternal organism. Quantitative parameters of cardiomyocyte myofibrils in different zones of the ventricular myocardium were determined using transmission electron microscopy. Results. In newborn rats, after exposure to ethanol, the values of the parameters in the subendocardial zone were statistically significantly increased in the left ventricle by 101.0% and in the right ventricle by 42.0%, compared to the indicators of the previous day of development. Indicators in the intramural and subepicardial zones were not significantly different from the corresponding values on the 20th day of prenatal ontogenesis. The difference between the parameters of different parts of the interventricular septum was statistically significant and amounted to 45.9% in the left ventricular part and 20.2% in the right ventricular part. The values of the parameter in the intramural zone after ethanol exposure decreased by 35.5% (p>0.05) in the left ventricle and by 36.0% (p<0.05) in the right ventricle compared to the norm. Conclusion. Chronic alcohol intoxication in prenatal cardiogenesis damages the contractile apparatus of ventricular cardiomyocytes due to disorganization of the structure of sarcomeres, fragmentation and disorientation of myofibrils, significant inhibition of sarcomere genesis, and a decrease in the content of myofibrils, which is associated with destruction of mitochondria. The severity of changes in these structures depends on the zone and period of development of the embryo. The most significant changes are due to the direct toxic effect of ethanol and occur in the early stages of cardiogenesis.

Immunohistochemical Characterization of Heart Left Ventricle Morphogenesis in Rats Fetuses

Rats are the most common objects of preclinical studies, which determines the relevance of studying fetal cardiomorphogenesis in rats using modern methods of morphological studies. The aim is to study the dynamics of markers of proliferation (Ki67), apoptosis (caspase 3), vascularization (CD31), and stromal remodeling (MMP2 and MMP9) of the left ventricular myocardium of Wistar rat fetuses. Material and methods. A histological, immunohistochemical and morphometric study of the rat heart left ventricle wall was carried out on the 18th, 19th, 20th, 21st and 22nd days of the prenatal period of ontogenesis. Results. From the 18th to the 22nd day of the prenatal period of ontogenesis in rats, a twofold increase in the thickness of the left ventricle lateral wall is observed, due to both proliferation and differentiation and an increase in the size of cardiomyocytes. Ki67-positive cardiomyocytes are diffusely localized in the wall of the left ventricle, their number increases on day 19 of the prenatal period of development and remains at a high level until the end of the prenatal period in rats. From the 18th to the 22nd day of the prenatal period of ontogeny in rats, single caspase 3-positive cardiomyocytes are detected in the left ventricle. The growth of the left ventricular myocardium in the fetal period in rats is accompanied by an adequate rate of vascularization. The vascularization and proliferation of cardiomyocytes are accompanied by remodeling of the myocardial stroma, with the highest intensity of MMP2- and MMP9-immune staining observed at the beginning of the fetal period of ontogeny in rats. Conclusion. The short duration of prenatal ontogenesis in rats determines the high dynamics of cardiomorphogenetic processes. In the fetal period of rat ontogenesis in the left ventricle of the heart, the proliferation of cardiomyocytes prevails over the intensity of apoptosis. The intensity of proliferation of cardiomyocytes of the left ventricle of rats is high up to the 22nd day of the prenatal period of ontogenesis.

IInformation-reference system on human brain development

BACKGROUND: Available information on the intrauterine maturation of the human brain is fragmentary; thus, the systematization of these data in the form of an information-reference system is needed. A modern solution would be the creation of a multimodal digital atlas, which would combine images of the developing brain at the macromorphological, tissue, and cellular levels.
 AIM: This study aimed to create a prototype of an informational reference system on human brain development, incorporating a digital multimodal atlas with the ability to view specific brain regions.
 METHODS: The creation of a prototype informational reference system on the prenatal morphogenesis of the human brain involved the following stages: researching the subject area, developing an informational model, defining automation tasks and functionality of the information system, selecting hardware and software tools, testing, and analyzing the results.
 RESULTS: A prototype of the informational reference system “Human Brain Development Atlas” was developed, consisting of three main blocks for each ontogenetic stage: (1) description of the brain development stage, which includes a macroscopic description of the brain structure, an overview of key morphogenetic events, and galleries with hematoxylin and eosin-, Nissl-, and Mallory-stained sections; reference atlases, which contains annotated maps of brain sections at different stages of prenatal ontogenesis; and 3) immunohistochemical atlases, which provides data on the developmental translational profile of brain cells. Currently, some materials are already available on the project website: https://brainmorphology.science/ru/
 CONCLUSIONS: Modern information technologies can be used for data collection and processing on the prenatal morphogenesis of the human brain. The creation of an informational reference system on the prenatal morphogenesis of the human brain can contribute to the development of new methods for early diagnosis and treatment of various nervous system disorders.
 The data presented in this article were previously published in English in “Life” (doi: 10.3390/life13051182) and are published in “Morphology” in Russian with the consent of the authors and copyright holders and in accordance with the terms of the CC BY license of the primary article.

The role of serotonin in prenatal ontogenesis

This review article summarizes current ideas about the role of serotonin in prenatal ontogenesis. We herein present the results of experimental and clinical studies that reveal the mechanisms of serotonin involvement in the establishment and development of the single mother-placenta-fetus system. The article highlights the key role of maternal serotonin in the genetic program for the morphological and functional development of fetal organs from the earliest stages of prenatal ontogenesis, in both normal and complicated pregnancy. We also discuss gestational factors that affect the production of maternal, placental, and fetal serotonin, as its deficiency or excess during pregnancy determines perinatal and long-term pathology programming in the offspring. The article substantiates the prospects for using serotonin as a biochemical marker of brain damage in a newborn for the timely application of neuroprotection and the prevention of adverse consequences.

Neuromorphological Atlas of Human Prenatal Brain Development: White Paper.

Recent morphological data on human brain development are quite fragmentary. However, they are highly requested for a number of medical practices, educational programs, and fundamental research in the fields of embryology, cytology and histology, neurology, physiology, path anatomy, neonatology, and others. This paper provides the initial information on the new online Human Prenatal Brain Development Atlas (HBDA). The Atlas will start with forebrain annotated hemisphere maps, based on human fetal brain serial sections at the different stages of prenatal ontogenesis. Spatiotemporal changes in the regional-specific immunophenotype profiles will also be demonstrated on virtual serial sections. The HBDA can serve as a reference database for the neurological research, which provides opportunity to compare the data obtained by noninvasive techniques, such as neurosonography, X-ray computed tomography and magnetic resonance imaging, functional magnetic resonance imaging, 3D high-resolution phase-contrast computed tomography visualization techniques, as well as spatial transcriptomics data. It could also become a database for the qualitative and quantitative analysis of individual variability in the human brain. Systemized data on the mechanisms and pathways of prenatal human glio- and neurogenesis could also contribute to the search for new therapy methods for a large spectrum of neurological pathologies, including neurodegenerative and cancer diseases. The preliminary data are now accessible on the special HBDA website.

Development of the basilar artery system in the human embryonic period

The doctrine of the origin and development of cerebral arteries in the embryonic period of man in the XIX – XXI centuries was formed by I. Tandler (1899, 1902), H. Evans (1911), G.L. Streeter (1908, 1918), G.D. Aronovich (1939), D.N. Padget (1947 – 1972), N.V. Popova-Latkina (1954 – 1975), Y.N. Shapovalov (1963), A.G. Knorre (1967), I. Stanek (1977), B. Carlson (1983), A.V. Gorbunov (1998 – 2022), etc. To date, we have shown that basilar arteries are detected in embryos at 7 weeks of intrauterine development, posterior cerebral arteries with plexiform branching – at 8 weeks of intrauterine life, and persistent trigeminal arteries continue to be detected in prenatal embryos at 8-9 weeks of human prenatal ontogenesis. In prenatal embryos 7-8-9 weeks of prenatal ontogenesis, the basilar artery system provides the needs of the human intrauterine brain.

Role of Albumin and Alpha-Fetoprotein in Prenatal Ontogenesis of the Human Eye

Role of Albumin and Alpha-Fetoprotein in Prenatal Ontogenesis of the Human Eye

Role of Albumin and Alpha-Fetoprotein in Prenatal Ontogenesis of the Human Eye

The vitreous body of the eye of human fetuses contains serum albumin (SA) and alpha-fetoprotein (AFP), which is normally characteristic of human embryos and fetuses. In the second trimester, both proteins are found in the vitreous at a concentration comparable to that in blood serum, after which their content decreases sharply. In this analytical review, taking into account the biological properties of SA and AFP, the role of these proteins in the processes of growth and differentiation of the structures of the developing eye is discussed.

Topographic and anatomical relationships of the lower jaw and auricle in human prenatal ontogenesis

Aim to describe the topographic and anatomical relationships of the fetal lower jaw and auricle in the mid-gestation period.
 Material and methods. The 110 mandibles of human fetuses of the second trimester were selected for the study and divided into groups by sex and age. The morphological techniques and the method of ultrasound scanning were used to determine the topographic relationships of the lower jaw and the fetal ear, the location of the central part of the auricle relative to the lower jaw (the line connecting the gnathion point and the external occipital protuberance) at different age periods.
 Results. During the mid-gestation period, with the growth of the fetus, the auricle normally shifts upward relative to the mandible. At the beginning of the study period, the auricle is located just below the angle of the lower jaw. Its central part (C) is below the line (AB) connecting the gnathion point and the external occipital protuberance. The perpendicular from the conditional center of the auricle to the line AB is half the diameter of the auricle 3.7 1.1 mm. In the second age group, the auricle is located at the level of the branch and angle of the lower jaw Its conditional center (C) is below the line AB and is of the diameter of the auricle 3.1 0.8 mm. By the end of the mid-gestation period, the auricle is displaced to the level of the processes of the lower jaw above the notch. Its central part is above line AB, the perpendicular from point C to line AB is 6.1 1.4 mm.
 Conclusion. The deviations in the formation of the topographic and anatomical relationships of the lower jaw and auricle of the fetus from 14 to 27 weeks of gestation can be additional criteria for the development of congenital fetal pathology and require the fetoabnormal alertness.

COMPOSITION AND PHYSICO-CHEMICAL PROPERTIES OF PROTEINS IN FETAL WATER IN COMPLICATED PREGNANCY

Relevance. The physiological course of prenatal ontogenesis largely depends on the state of the amniotic fluid, which largely provides the fetus with the substances necessary for its development. Among the complications of pregnancy, premature birth leads to especially serious consequences. In this regard, the elucidation of the mechanisms for unleashing labor activity before the term is important. The most informative for achieving these goals are proteins that perform numerous functions in the regulation of cellular metabolism. Purpose of the study. To study the composition and properties of amniotic fluid proteins and the significance of their changes in predicting preterm birth. Material and methods. The study included 29 healthy women with uncomplicated pregnancy and delivery at term (control group) and 35 women who developed labor activity at 34-37 weeks (main group). In amniotic fluid taken at 16-18 weeks (by transabdominal amniocentesis), the spectrum of proteins and a number of their physicochemical properties were determined using electrophoresis, chromatography, spectrophotometry and densitom-etry methods. Results. It has been established that the development of preterm labor occurs against the background of modification of protein-protein interactions and complexing of proteins with non-protein compounds. Conclusions. The revealed imbalance of the protein composition may be an important link in the chain of functional and molecular disorders leading to preterm birth.

Профили астроцитарной дифференцировки переднего мозга человека на внутриутробном этапе онтогенеза

Introduction. Brain functioning is kept by both neuronal cell activity and macroglia, i.e., astrocytes and oligodendrocytes. The current data on the prenatal development of the human brain are scarce, and gliogenesis is less studied than cortical neurogenesis. Normal limits and variations and spatiotemporal patterns of glial differentiation in human brain development remain poorly studied. Materials and methods. We used human fetal autopsy samples from the Collection of the Laboratory of Nervous System Development of Avtsyn Research Institute of Human Morphology. For immune and morphological analysis, samples of 38 fetal cerebral hemispheres at stages from 8 postconceptional weeks to birth were chosen. Results. We provided the results of the pilot comparative immune and morphological study with the panel of markers (GFAP, ALDH1L1, FABP-7) of the fetal human telencephalon in prenatal ontogenesis. Specific differentiation and maturation of the astrocyte population on the telencephalon start before early fetal period (12–13 gestational weeks). GFAP+ and ALDH1L1+ astrocyte populations in early human telencephalon are still to be studied for their homology. Analysis of GFAP+ and ALDH1L1+ glioblast distribution proposes dorsal proliferative zone as a source for fibrous cortical astrocytes. Comparative immune and morphological analysis of FABP-7+ neuroblasts in the fetal telencephalon questions whether FABP-7 cells belong to astrocyte population at early prenatal human ontogenesis. Conclusion. In the telencephalon, temporal and/or spatiotemporal translational profiles of these three antigens differ, which indicates that the astrocyte population is heterogeneous in early ontogenesis. Keywords: human brain development, telencephalon, glial differentiation, astrocytes, astrocyte fate lineage, GFAP, ALDH1L1, FABP-7

СТРУКТУРНАЯ ХАРАКТЕРИСТИКА НАЧАЛЬНЫХ ЭТАПОВ ЭМБРИОНАЛЬНОГО МОРФОГЕНЕЗА МЕТАНЕФРОСА У СИРИЙСКОГО ХОМЯКА (MESOCRICETUS AURATUS)

A study of the embryogenesis of a permanent kidney at the stages of prenatal ontogenesis in a Syrian hamster (Mesocricetus auratus) was conducted. It was found that the laying of metanephros occurs at stage 16 of development by the interaction of metanephrogenic blastema and metanephrogenic diverticulum.

FEATURES OF MORPHOGENESIS OF THE BONES OF THE HUMAN ORBIT.

The aim: To find out the sources of origin, the chronology of ossification, the peculiarities of age-related topographical and anatomical changes in the bones of the human orbit. Materials and methods: The research was carried out on the specimens of 18 human embryos and prefetuses aged from 4th to 12th weeks of intrauterine development and 12 human fetuses aged from 4th to 9th months which were studied by microscopic examination and 3D reconstruction. Results: The first signs of osteogenesis around the main nervous and visceral contents of the orbit rudiment are observed in 6-week-old embryos in the form of seven cartilaginous bone models. The first signs of ossification in the region of the orbit are found in the maxilla. During the 6th month of intrauterine development, intensive processes of ossification of the frontal, sphenoidal, ethmoidal bones and maxilla are noticeable. From the beginning of the fetal pe¬riod of human ontogenesis, the ossification of bone rudiments that form the walls of the orbit continues. The processes of ossification of the structures of the sphenoidal bone continue, which leads to morphological transformations of the orbit in 5-month-old fetuses - it is separated from the sphenopalatine and infratemporal fossae by a bone layer, the optic canal is formed, and in 6-month-old fetuses, processes of ossification of the frontal, sphenoidal and ethmoidal bones and maxilla occur, Müller's muscle changes its structure to a fibrous one. Conclusions: Critical periods of the orbit development are the 6th month of prenatal ontogenesis and the 8th month.

BASILAR ARTERY OF THE HUMAN EMBRYO: THE BEGINNING OF FORMATION

In order to study the features of the development of the basilar artery, the authors analyzed 4 series of sagittal sections and 2 series of frontal sections of human embryos from 21 mm to 27 mm crown-rump length. The primary basilar artery is detected at 7 weeks of fetal development. It turned out that in embryos of 7–8 weeks of human prenatal ontogenesis, the arteries already vascularize the brain well, and the arterial bed of the human brain can be ready for functioning. The data obtained indicate the emergence of the irrigation system of the basilar artery at the age of 8 weeks of intrauterine development in humans. The analyzed stages of embryos are assumed as a kind of spurt for the development of the arterial system of the human brain and determine the need for further fundamental longitudinal study of human embryogenesis.

The effect of Adrenaline on the contractility of the Right Ventricular Myocardium in rat pups with altered Serotonin concentration in Ontogenesis

Serotonin is a monoamine neurotransmitter and hormone that exerts its various actions by binding to the receptor membrane in cells. 5-HT2B receptors are actively involved in embryonic morphogenesis and regulate the development of the heart. 5-HT4 and 5-HT2B are involved in myocardial contractility and affect the temporal parameters of regulation. One of the main mechanisms controlling cardiac activity is also connected with the effect of catecholamines on adrenergic receptors of cardiomyocytes, which mediate the action of the sympathetic nervous system, being the main factor contributing to multiple changes in the development of myocardial cell function. In the given study, there is reliable data provided to indicate that the effect of different concentrations of adrenaline leads to a decrease in contractility of the right ventricular myocardium in 7-day-old and 14-day-old rat pups with an altered serotonin concentration, which was created by a blockade of the synthesis of serotonin and the membrane serotonin transporter in the embryonic period of ontogenesis. The total duration of myocardial contraction is decreased in experimental groups of animals. Thus, the smallest decrease in the time of contraction and relaxation in comparison with other groups is observed in 7-day-old rat pups with an excess of serotonin; in 14-day-old rat pups with a lack of serotonin. Thus, a change in the concentration of serotonin in prenatal ontogenesis can possibly affect the sensitivity of adrenergic receptors in postnatal ontogenesis.

Morphological, immuno- and lectinohistochemical evaluation of the lymphoid apparatus of the human fetal appendix

Aim. To identify the morphological and functional features of the human appendix lymphoid formations in the late period of prenatal ontogenesis. Materials and methods. The vermiform appendices from 42 human fetuses of both sexes without anomalies, diseases of the gastrointestinal tract, immune system and hematopoiesis were examined. Histological, lectinohistochemical (PNA+, SBA+), immunohistochemical (expression of markers CD3+, CD4+, CD8+, CD20+, CD34+, CD68+, Ki-67, caspase 3+), morphometric methods of examination were used with statistical analysis of the obtained results. Results. Single lymphocytes are seen near venules in the mucous membrane of the human fetal vermiform appendix at 16–18 weeks’ gestation; the lymphocytes are aggregated to form the lymphoid follicles at the 25th week. The lymphoid follicles are populated by small- and medium-sized lymphocytes, macrophages, cells at the stages of apoptosis (Caspase 3+) and proliferation (Ki-67+), reticular cells. From the 28th week of the prenatal period, lymphoepithelial nodules are detected compositionally resembling perivascular ones. In the subepithelial and peripheral zones of the nodules, there are lymphocytes expressing CD3 and PNA receptors, in the central zone – CD20 and SBA receptors, macrophages (CD68+/PNA+/SBA+), cells at the stage of proliferation (Ki-67+) and apoptosis (caspase 3+). By the end of the fetal period, the lymphoid follicles of the human appendix contain fewer T-lymphocytes (CD3+) and an increased number of B-lymphocytes (CD20+) and macrophages (CD68+), which are localized mainly in the central zone, however, the germinal centers are not yet formed. Conclusions. In the developmental process of the vermiform appendix lymphoid tissue during the prenatal period of ontogenesis, the following critical periods were noted: the 16th–18th weeks – the appearance of lymphocytes in the lamina propria, the 25th week – the formation of perivascular lymphoid follicles near venules, the 28th week – the appearance of lymphoepithelial nodules. The number of T-lymphocytes (CD3+) was decreased in the lymphoid follicles, while the number of B-lymphocytes (CD20+) and macrophages (CD68+) was increased with age.