Vol 164, No 2 (2026)
- Year: 2026
- Published: 23.03.2026
- Articles: 11
- URL: https://j-morphology.com/1026-3543/issue/view/13060
- DOI: https://doi.org/10.17816/morph.20261642
Historical articles
Development of fundamental and applied problems of histology in the works of Alexander A. Braun (1904–1984)
Abstract
The article is devoted to one of the prominent representatives of the scientific histological school of Academician Alexey A. Zavarzin — the distinguished Soviet histologist, Doctor of Sciences in Biology, Professor Alexander A. Braun (1904–1984). From 1931 to 1950, after graduating from Leningrad University and completing postgraduate training at the Department of Histology, he worked at higher education institutions and research institutes in Leningrad. By the late 1930s, Alexander A. Braun had become one of the country’s leading histologists. Owing to developments in biology and medicine in the late 1940s, he was forced to leave Leningrad. From 1950 to 1972, Braun headed departments of histology at medical universities in Kyrgyzstan (Frunze) and Tajikistan (Dushanbe). His scientific research was devoted to problems of comparative and evolutionary histology, issues of intertissue correlations, the relationships between epithelium and connective tissue, the features of morpho- and histogenesis, as well as to the identification of patterns of reparative histogenesis. Based on comparative studies of vertebrate skin, Braun identified patterns of evolutionary transformation of the integument, in particular demonstrating parallelism in the dermal structure of fish and aquatic mammals. He described features of the morphofunctional organization of the thyroid gland in various mammals and the dynamics of its seasonal changes. Together with Mikhailov, Braun outlined and implemented approaches to synthesizing Zavarzin’s theory of parallelism in tissue evolution and Khlopin’s theory of divergent tissue evolution. They proposed that tissue evolution in phylogeny proceeds through parallelism of their divergent changes. Braun developed an original classification of post-traumatic organ regeneration patterns in vertebrates. Studies of regeneration under high-altitude conditions demonstrated that relocation of animals from lowland to highland environments reduces their adaptive and reparative capacities, and that wound healing in such conditions proceeds significantly more slowly. As adaptation to high-altitude conditions occurs, resistance to damaging factors and reparative potential are restored. The results of Alexander A. Braun’s research became a fundamental basis for adaptive medicine. He established a major scientific histological school that continues to develop the outlined research directions to this day.
118-128
Reviews
Notochord: morphogenesis, structure, and functional significance
Abstract
The notochord represents a defining synapomorphy of the phylum Chordata, serving as the primary axial skeleton and a crucial embryonic organizer. This review systematizes current concepts regarding the evolutionary origin, molecular mechanisms of morphogenesis, and structural–functional organization of the notochord. Major evolutionary hypotheses — dorsoventral inversion and aboral dorsalization — are examined and compared in the context of vertebrate body plan formation.
The hierarchical gene regulatory network underlying notochord development is described in detail, with emphasis on the central role of the transcription factor TBXT (Brachyury) and the Wnt/PCP, Hedgehog, and Notch signaling pathways. Molecular and cellular mechanisms of convergent extension, formation of the perinotochordal sheath, and cellular vacuolization — processes that generate turgor pressure and mechanical stiffness — are analyzed. Particular attention is given to notochord formation in humans, from the stage of the notochordal plate to its postnatal transformation into the nucleus pulposus of the intervertebral discs.
The clinical relevance of residual progenitor cell populations within the nucleus pulposus expressing the markers Tie2 and GD2 is discussed. Their role in maintaining homeostasis within the avascular intervertebral disc, the association between depletion of this cell pool and the development of degenerative spinal disorders, and their potential applications in regenerative medicine are considered. The review also addresses issues related to the molecular diagnosis of chordoma as a tumor of notochordal origin.
129-146
Structural and morphological changes of the human umbilical cord in complicated pregnancy
Abstract
The close interaction between two circulatory systems separated by the placental barrier determines the sensitivity of the fetoplacental circulation to critical disturbances of maternal blood flow within the intervillous space of the placental cotyledon and to activation of hemostatic processes on the surface of chorionic villi. Maternal somatic diseases manifesting as by hypertension and metabolic disorders during pregnancy affect the development and function of the placenta and umbilical cord. Because structural alterations in the umbilical cord vessel walls appear earlier than in fetal vessels and are associated with placental vascular resistance, detailed morphological assessment of the umbilical cord may improve prediction of neonatal health outcomes.
The aim of this study is to review published data describing the morphological and functional features of the umbilical cord in infants born to mothers with complicated obstetric histories.
Studies of umbilical cords from infants born to mothers with preeclampsia have demonstrated narrowed umbilical artery lumen associated with thickening or edema of the vascular smooth muscle layer. Reduced Wharton jelly has not been consistently observed; in only one study was it accompanied by thickening of the vascular muscular layer. In contrast, another study reported an increased volume of Wharton jelly. No morphological changes in the umbilical vein wall were detected in all studies. Thickening of the umbilical vein wall may have compensatory significance, whereas thinning appears to be pathological. Morphological changes of the umbilical vein in fetuses with intrauterine growth restriction and in preterm infants have not been described. Furthermore, detailed investigation is required to clarify the role of tissue factors, including matrix metalloproteinases and vascular endothelial growth factor, in shaping the morphological characteristics of the umbilical cord.
Comprehensive evaluation of morphological and structural alterations of the umbilical cord and its components in large cohorts of pregnant women with various somatic diseases may improve the predictive accuracy of neonatal health outcomes and the risk of fetal developmental abnormalities.
147-157
Right atrium of the human heart: analysis of contemporary concepts of typical and variant anatomy
Abstract
This review summarizes and systematizes published data on the normal (typical and variant) anatomy of the human right atrium.
Most researchers agree that the right atrium consists of the sinus venarum cavarum, the atrial body, the right atrial appendage, and the vestibule of the tricuspid valve with the cavotricuspid isthmus. The dimensions and shape of the atrial body and appendage exhibit individual and typological variability; however, in the reviewed scientific sources, no data were found regarding the dependence of these parameters on sex or age. Various patterns of the internal surface features of the right atrial walls have been described, but existing classifications are largely based on subjective criteria, which reduces their accuracy and reproducibility. The true interatrial septum is represented only by the floor and the limbus of the fossa ovalis rather than the entire medial wall of the atrium. In 15%–35% of heart specimens from patients who died of noncardiac causes, an interatrial communication is present anterior to the fossa ovalis. A review of the scientific data showed that publications on the anatomy of the normal human right atrium are, for the most part, devoted to individual aspects of the structure of its parts and components, whereas comprehensive studies of the typological and variant anatomy of the walls and subdivisions of this cardiac chamber are few. Studies aimed at developing features of the normal structure of the right atrium, substantiated from the standpoint of morphometry and ontogeny and based on the methodology of evidence-based anatomy, are currently relevant.
158-170
Sympathoblasts and their malignant progeny: the cellular mosaic of neuroblastoma
Abstract
This review provides a comprehensive analysis of current knowledge on neuroblastoma in the context of embryonic development of the sympathoadrenal system. The evolution of scientific concepts regarding this tumor is traced from its first descriptions in the second half of the 19th century to the present day. The review outlines the conceptual framework of the modern understanding of neuroblastoma as a consequence of disrupted differentiation of neural crest cells. Particular attention is given to embryological aspects of sympathoadrenal system development, including neural crest cell migration, differentiation under the influence of external signals, and the formation of bipotential sympathoblasts capable of generating both neuronal and mesenchymal lineages. A substantial portion of the review focuses on the cellular heterogeneity of neuroblastoma, manifested by the coexistence of H-type (adrenergic) neuronal cells and C-type (mesenchymal) adhesive cells. The authors analyze findings from recent studies and highlight challenges in identifying tumor cell populations, emphasizing the need for validated species-specific markers. The review underscores the importance of integrating knowledge of key embryogenic stages with modern genomic technologies to develop more effective therapeutic strategies for this aggressive pediatric tumor.
171-181
Original Study Articles
Identification of key fetometric markers for predicting neonatal birth weight based on ultrasound fetometry using classical and machine-learning algorithms
Abstract
BACKGROUND: Accurate prediction of neonatal birth weight using ultrasound fetometry remains a relevant challenge in modern perinatology. Despite numerous studies in this field, a gap persists in defining the optimal combination of fetometric parameters required for precise estimation of fetal birth weight, which substantially affects timely diagnosis of intrauterine growth restriction.
AIM: To determine the contribution of individual fetometric parameters to predicting neonatal birth weight and to develop an optimal fetal weight estimation model based on comprehensive analysis of ultrasound measurement data.
METHODS: This retrospective study used data from 5161 full-term neonates and 8022 fetal ultrasound examinations. The dataset included neonates with complete clinical information for the main fetometric parameters available. The observation period covered the interval from the first ultrasound examination to delivery. The primary endpoint was neonatal birth weight measured at birth. To assess parameter contributions, descriptive and correlation analyses, multiple linear regression, quantile regression with coefficients reported to three decimal places, and machine-learning methods (Random Forest and XGBoost) were applied. Additionally, principal component analysis was performed to derive a general fetal growth factor, enabling integration of multiple fetometric measurements into a single composite indicator that more reliably reflects overall fetal size and is more closely associated with birth weight.
RESULTS: Abdominal circumference showed the strongest correlation with birth weight (r = 0.820), whereas femur length and head circumference demonstrated correlations of r = 0.620 and r = 0.540, respectively. Multiple regression including these three parameters yielded R2 = 0.730. Quantile regression showed that the coefficient for abdominal circumference increased at the upper weight quantile (β = 23.500 at τ = 0.900) compared with the median (β = 18.900 at τ = 0.500). Machine-learning methods confirmed the dominant role of abdominal circumference in birth weight prediction (feature importance 50%–55%). Principal component analysis indicated that the first principal component, interpreted as a general size measure, explained 78% of the variance and was highly correlated with birth weight (r = 0.850).
CONCLUSION: These findings indicate that abdominal circumference is the most informative fetometric parameter for predicting fetal birth weight, whereas femur length provides complementary information by reflecting skeletal growth. Head circumference contributes minimally. The combined use of classical statistical approaches and machine-learning algorithms supports prioritizing accurate measurement of abdominal circumference and femur length when estimating fetal weight.
182-191
Progenitor and bihormonal cells in neuroinsular complexes of the developing human pancreas
Abstract
BACKGROUND: The development of effective treatments for diabetes mellitus directly depends on a comprehensive understanding of the mechanisms underlying endocrine cell differentiation and pancreatic islet morphogenesis. Experimental studies have demonstrated that the nervous system plays an important role in regulating these processes. In the developing human pancreas, neural structures closely interact with hormone-containing cells, forming neuroinsular complexes, as well as with epithelial cells, suggesting a potential involvement of the nervous system in pancreatic islet development. To support this hypothesis, data on interactions between neural structures and cells exhibiting a progenitor immunophenotype are essential; however, such data are currently lacking in the scientific sources.
AIM: To investigate the distribution of cells expressing the transcription factor PDX1 and bihormonal cells within neuroinsular complexes during human pancreatic development.
METHODS: The study was performed on autopsy specimens of the pancreas obtained from 15 human fetuses (gestational age of 9–25 weeks). Multiple immunofluorescence staining and confocal microscopy were used. To assess the cellular composition of neuroinsular complexes, various combinations of antibodies were applied: against endocrine cell hormones (insulin, glucagon, somatostatin), against the transcription factor PDX1 (pancreatic and duodenal homeobox 1), and against the neural marker neuron-specific β3-tubulin.
RESULTS: Triple immunofluorescence staining with antibodies against insulin, PDX1, and β3-tubulin revealed cells with a progenitor immunophenotype characteristic of ductal epithelial cells within neuroinsular complexes: insulin−/PDX1+/β3-tubulin− and insulin−/PDX1+/β3-tubulin+ cells. Starting from the 9th week of gestation, such cells were detected in isolated ganglia, and from the 14th week onward, in ganglia integrated with pancreatic islets within neuroinsular complexes. In specimens stained with insulin/glucagon/β3-tubulin and insulin/somatostatin/β3-tubulin antibody combinations, bihormonal insulin+/glucagon+ and insulin+/somatostatin+ cells were identified within neuroinsular complexes.
CONCLUSION: The present study demonstrates spatial integration of neural structures with cells exhibiting a progenitor immunophenotype and with bihormonal cells in the developing human pancreas. These bihormonal cells are regarded by most authors as endocrine cells at a stage of differentiation and maturation. Such integration may be necessary for the regulation of β-cell mass and maturation, as well as for modulation of pancreatic islet morphogenesis, as previously shown in experimental studies in animal models and cell cultures.
192-205
Trends of Bcl-2-positive lymphocytes in different zones of the splenic white pulp in rats after soft tissue injury of the thigh: a morphometric analysis
Abstract
BACKGROUND: Soft tissue injuries constitute a substantial proportion of musculoskeletal damage and are frequently associated with complications related to immune response dysregulation, including secondary infections and delayed wound healing. Understanding systemic alterations in immune organs, particularly the spleen, is essential for developing strategies aimed at optimizing regeneration and preventing complications. Although the role of Bcl-2 (B-cell lymphoma 2) protein in the regulation of apoptosis is well established, data on its expression in the spleen following soft tissue injury remain limited. Most studies focus on local wound-site changes, whereas systemic effects, especially in lymphoid organs, have been insufficiently investigated.
AIM: To investigate changes in the number of Bcl-2-positive lymphocytes in different zones of the splenic white pulp in rats after soft tissue injury of the thigh using immunohistochemical and morphometric analysis.
METHODS: The study was performed on male outbred white rats weighing 180–200 g. Mechanical thigh injury comparable in kinetic energy to a 5.6-mm caliber bullet wound was induced using a specialized device (under ether anesthesia). Animals were euthanized by decapitation. Spleen specimens measuring 0.5 × 1.5 cm were collected at 1, 3, 7, and 14 days after injury for morphometric and immunohistochemical examination. Tissue sections were stained with hematoxylin and eosin. Immunohistochemistry was performed to detect cells expressing the antiapoptotic protein Bcl-2, T lymphocytes (CD3), and B lymphocytes (CD19), with Mayer’s hematoxylin nuclear counterstaining. Statistical analysis was conducted in R software (version 4.3.2) using the packages dplyr, tidyr, car, rstatix, pwr, ggplot2, and ggpubr.
RESULTS: Mechanical thigh injury in rats led to changes in the number of Bcl-2-positive lymphocytes in various splenic zones. A transient decrease in these cells was observed at 1 and 3 days post-injury, likely associated with lymphocyte migration to peripheral tissues, followed by gradual restoration and even increased Bcl-2 expression in the spleen by day 14.
CONCLUSION: An increase in Bcl-2-positive lymphocytes reflects a systemic immune response to local soft tissue injury of the thigh. This response may contribute to host defense against infections but could potentially delay wound healing when excessively activated. The association between local and systemic immune responses underscores the important regulatory role of the spleen and justifies further investigation to optimize therapeutic strategies for injury management.
206-220
Gene expression of cytokines and wound-healing potential of macrophages derived from rat bone marrow and peripheral blood
Abstract
BACKGROUND: Macrophages are key regulators of inflammation and tissue regeneration and represent a promising tool for cell therapy. In rats, functional differences between macrophages derived from red bone marrow and peripheral blood remain insufficiently studied, particularly in the context of wound healing, where L-arginine metabolism plays a critical role.
AIM: To compare the expression levels of regulatory and proinflammatory cytokine genes (interleukin-1β, -6, and -10) and genes encoding L-arginine–metabolizing enzymes (Arg1 and NOS2) in macrophages derived from bone marrow monocyte precursors and peripheral blood monocytes, and to assess their effects on cutaneous wound healing.
METHODS: Macrophages were generated from red bone marrow monocyte precursors and peripheral blood monocytes of Sprague–Dawley rats using recombinant macrophage colony-stimulating factor (rM-CSF). Macrophage phenotype was established using immunocytochemistry (staining for CD68 and CD43 markers). Gene expression levels were determined by real-time polymerase chain reaction and normalized to β2-microglobulin (β2M). The effects of macrophages on cutaneous wound healing were evaluated in vivo. Statistical analysis was performed using the Mann–Whitney U test (p < 0.05).
RESULTS: Macrophages from both sources expressed CD68 and CD43. Red bone marrow (RBM)–derived macrophages demonstrated higher expression levels of IL-6 and IL-10 genes (p = 0.029 and p = 0.027, respectively), whereas peripheral blood (PB)–derived MPs showed higher expression of Arg1 and NOS2 (p = 0.029 for both genes). Administration of PB-derived macrophages did not result in complications, whereas RBM-derived macrophages were associated with wound bleeding. No accelerated wound healing was observed in either group.
CONCLUSION: RBM-derived macrophages exhibit enhanced activation potential, whereas PB-derived macrophages demonstrate a more pronounced influence on tissue regeneration. For cell-based therapy, PB-derived macrophages appear preferable due to a lower risk of complications. These findings highlight the importance of further investigation into the source-dependent activity of macrophages in reparative processes.
221-234
Detection of brain macrophages in rats using different anti-CD68/macrosialin antibodies
Abstract
BACKGROUND: Macrophages represent a heterogeneous cell population with diverse origins, phenotypic characteristics, and functional properties. In the brain, resident macrophages are associated with barrier structures, including the meninges, blood vessels, and choroid plexus. Anti-CD68/macrosialin antibodies are commonly used to identify macrophages. Published data and experimental experience indicate a low degree of conservation of this protein, necessitating the use of species-specific antibodies and careful selection of primary reagents for macrophage detection in laboratory rodent tissues.
AIM: To perform a comparative analysis of macrophage detection in rats using rabbit polyclonal anti-CD68 antibodies and mouse monoclonal antibodies of the ED1 clone.
METHODS: Brain sections obtained from Wistar rats (n = 6) were examined; heart and liver sections from the same strain served as controls. CD68/macrosialin-positive macrophages were identified using mouse monoclonal antibodies (clone ED1) and rabbit polyclonal antibodies in various immunohistochemical staining protocols.
RESULTS: Both antibody types specifically detected brain macrophages in three locations: the pia mater, vascular walls, and the choroid plexus. Rabbit polyclonal antibodies demonstrated higher intensity of specific staining compared with mouse monoclonal antibodies, with no nonspecific binding observed. The use of mouse monoclonal antibodies required heat-induced antigen retrieval and blocking reagents within the staining protocol.
CONCLUSION: Comparative analysis of macrophage detection in rat brain sections using antibodies of different origins and clonality demonstrated that rabbit polyclonal antibodies provide reliable macrophage labeling using a simpler immunohistochemical protocol compared with mouse monoclonal antibodies. Therefore, rabbit polyclonal antibodies may be recommended as a useful alternative for CD68/macrosialin staining in rat tissue sections.
235-244
Short communications
Perivascular macrophages of rat liver do not express CD68 marker
Abstract
BACKGROUND: Tissue macrophages play a key role in regulating hepatic tissue homeostasis. At the same time, they represent a heterogeneous population of cells in terms of both phenotypic and functional characteristics.
AIM: To characterize the immunophenotype of rat liver macrophages using the phagocytic activity marker CD68 and the microglial marker Iba-1.
METHODS: Liver and brain samples from Wistar rats (n = 8) were used. Double immunohistochemical staining was performed using antibodies against CD68 and Iba-1 (ionized calcium-binding adapter molecule 1). Specimens were analyzed using confocal laser scanning microscopy.
RESULTS: Iba-1-positive cells identified in the specimens corresponded to interstitial macrophages and Kupffer cells. CD68- positive macrophages were detected along hepatic sinusoidal capillaries and between hepatocytes. Co-expression of CD68 and Iba-1 was observed in Kupffer cells in the liver and in perivascular macrophages in the brain, but not in perivascular macrophages localized in the portal triads or in the interlobular connective tissue.
CONCLUSION: The colocalization of Iba-1 and CD68 in brain perivascular macrophages and the absence of their co-expression in hepatic interstitial macrophages indicate organ-specific phenotypic features of perivascular phagocytes.
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