Days Of Postnatal Development Research Articles

INFLUENCE OF MATERNAL SUBHEPATIC CHOLESTASIS ON KIDNEY DEVELOPMENT IN SECOND-GENERATION OFFSPRING

Background. Maternal cholestasis of pregnancy was found to have a negative effect on the kidney structure of firstgeneration offspring. It is not known whether changes in the urinary system will occur in second-generation offspring. Objective. To establish the peculiarities of kidney development in second-generation offspring from rats with cholestasis of pregnancy. Material and methods. Second generation 15-, 45- and 90 day-old rats born from males and females developed in maternal cholestasis. Surgical, somatometric, histological, morphometric and statistical methods of research were used in the experiment. Results. Maternal cholestasis induced on the 17th day of pregnancy leads to structural changes in the kidneys of second-generation offspring. These changes include a decrease in the weight of kidneys of experimental animals, a decrease in the width of their cortical substance, a decrease in the diameter of convoluted proximal and distal tubules of nephrons and the development of structural abnormalities in the epitheliocytes of tubule sections. Hypoplastic changes in renal nephrons persist up to 90 days of postnatal development of animals. Conclusions. Maternal cholestasis induces hypoplastic abnormalities in the kidneys of second-generation rats.

Light drives the developmental progression of outer retinal function.

The complex nature of rod and cone photoreceptors and the light-evoked responsivity of bipolar cells in the mature rodent retina have been well characterized. However, little is known about the emergent light-evoked response properties of the mouse retina and the role light plays in shaping these emergent responses. We have previously demonstrated that the outer retina is responsive to green light as early as postnatal day 8 (P8). Here, we characterize the progression of both photoreceptors (rods and cones) and bipolar cell responses during development and into adulthood using ex vivo electroretinogram recordings. Our data show that the majority of photoreceptor response at P8 originates from cones and that these outputs drive second-order bipolar cell responses as early as P9. We find that the magnitude of the photoresponse increases concurrently with each passing day of postnatal development and that many functional properties of these responses, as well as the relative rod/cone contributions to the total light-evoked response, are age dependent. We compare these responses at eye opening and maturity to age-matched animals raised in darkness and found that the absence of light diminishes emergent and mature cone-to-bipolar cell signaling. Furthermore, we found cone-evoked responses to be significantly slower in dark-reared retinas. Together, this work characterizes the developmental photoresponsivity of the mouse retina while highlighting the importance of properly timed sensory input for the maturation of the first visual system synapse.

Postnatal ontogeny of Neuromedin S and its receptors NMUR1 and NMUR2 expression in mouse testis

Neuromedin S (NMS) is a well-known anorexigenic neuropeptide. Despite some reports of the presence of its transcript and precursor protein in testis, the expression and localization of NMS and its receptors during the postnatal development of mammalian testis remains elusive. We investigated the expression patterns and testicular localization of NMS and its receptors NMUR1 and NMUR2, during 5, 10, 20, 30, and 90 days of postnatal development, using real time PCR, immunoblot analysis and immunohistochemistry in mice. NMS and its receptors are present at all age groups at transcript level in mouse testis. At the protein level, NMS and NMUR2 are present in all age groups, whereas NMUR1 is present primarily in 30- and 90-day testis. Immunolocalization study showed that NMS and NMUR2 are expressed in spermatogonia, spermatocytes, Sertoli cells, and Leydig cells, in contrast to NMUR1 which is expressed exclusively in the Leydig cells of 30- and 90-day testis. The results also confirm the intranuclear localization of NMS in spermatogonia and spermatocytes. Although NMS-NMUR2 is expressed in Sertoli cells at all stages of the spermatogenic cycle, they showed a stage-specific expression pattern in spermatogonia and primary spermatocytes. In conclusion, NMS and its receptors NMUR1 and NMUR2 are expressed in the testis and may regulate spermatogenesis, possibly by modulating steroidogenesis and Sertoli cell function in the testis.

CBA strain mice as a model of spontaneous carcinogenesis

The review analyzes some parameters of CBA mice-males as model of spontaneous carcinogenesis characterizing adhesive and adaptive disorders. A weakening of the hepatocytes mutual adhesiveness force was noted already in early ontogenesis (5–10 days of postnatal development). This violation persisted and enhanced during hepatocarcinogenesis. A decrease of the β2 leukocyte integrins LFA-1 and Mac-1 expression on peripheral blood cells as well as an increase of the interleukins 6 and 10 in blood serum were determined during ontogenesis. It is significant for weakening the liver cells contact interactions (mutual adhesiveness) as well as immunity effectors and tumor cells interactions. A disbalance of the adaptive reactions and life quality important components was revealed in the CBA mice-males ontogenesis. Number of dopaminergic neurons and the neurogenesislevel in CBA micemales were decreasing. This does not contradict the dynamics of chronic stress and the aging process: an increase in the catabolic stress hormone corticosterone, a decrease in the anabolic hormone testosterone in the blood serum, a decrease in motor activity, signs of cachexia and alopecia, as well as a violation of immunological parameters.CBA mice-males with an assessment of parameters characterizing adhesive and adaptive disorders during spontaneous carcinogenesis (the hepatocytes mutual adhesiveness forсe, the expression of β2 leukocyte integrins LFA-1 and Mac-1 on peripheral blood cells, the content of interleukins 6, 10, corticosterone and testosterone in blood serum, the number of dopaminergic neurons in the midbrain during ontogenesis) as well as the frequency and size of tumours, lifespan and somatic status of animals can be used as a scientifically- and evidence-based test system to study cytostatic drugs as well as non-toxic geroprotective medications for prevention and treatment of cancer in individuals with an increased risk of malignant neoplasms developing especially hepatocellular carcinoma.

Feeding mode influences dynamic gut microbiota signatures and affects susceptibility to anti-CD3 mAb-induced intestinal injury in neonatal mice.

Feeding modes influence the gut microbiome, immune system, and intestinal barrier homeostasis in neonates; how feeding modes impact susceptibility to neonatal gastrointestinal (GI) diseases is still uncertain. Here, we investigated the impact of dam feeding (DF) and formula feeding (FF) on features of the gut microbiome and physiological inflammation during the first 2 days of postnatal development and on the susceptibility to intestinal injury related to the inflammatory state in neonatal mouse pups. 16S rRNA sequencing data revealed microbiome changes, lower α-diversity, and a distinct pattern of β-diversity including expansion of f_Enterobacteriaceae and f_Enterococcaceae in the ileum of FF pups compared with DF pups by postnatal day (P)2. Together with gut dysbiosis, the FF cohort also had greater ileal mucosa physiological inflammatory activity compared with DF pups by P2 but maintained normal histological features. Interestingly, FF but not DF mouse pups developed necrotizing enterocolitis (NEC)-like intestinal injury within 24 h after anti-CD3 mAb treatment, suggesting that FF influences the susceptibility to intestinal injury in neonates. We further found that NEC-like incidence in anti-CD3 mAb-treated FF neonatal pups was attenuated by antibiotic treatment. Collectively, our data suggest that FF predisposes mouse pups to anti-CD3 mAb-induced intestinal injury due to abnormal f_Enterobacteriaceae and f_Enterococcaceae colonization. These findings advance our understanding of FF-associated microbial colonization and intestinal inflammation, which may help inform the development of new therapeutic approaches to GI diseases like NEC in infants.NEW & NOTEWORTHY This report shows that a feeding mode profoundly affects gut colonization in neonatal mice. Furthermore, our results demonstrate that formula feeding predisposes mouse pups to anti-CD3 mAb-induced necrotizing enterocolitis (NEC)-like intestinal injury upon inadequate microbial colonization. The study suggests the role of the combined presence of formula feeding-associated dysbiosis and mucosal inflammation in the pathogenesis of NEC and provides a new mouse model to study this disease.

Postnatal Organellogenesis in Histaminergic Neurons of the Rat Brain

The organellogenesis of histaminergic neurons in the nucleus E2 of the rat hypothalamus on the 5^th, 20^th, and 45^th days of postnatal development was described using the electron microscopic method of investigation.

Impact of Prenatal and Postnatal Exposure to Endocrine Disrupter DDT on Adrenal Medulla Function

Epinephrine is the most abundant catecholamine hormone, produced by the nervous system and adrenal glands. Endocrine disruption of epinephrine synthesis, secretion and signaling is less studied than steroid and thyroid hormones. Dichlorodiphenyltrichloroethane (DDT) is recognized as one of the most prominent environmental contaminants with a long half-life. It is a potent endocrine disrupter affecting sex steroid, mineralocorticoid, glucocorticoid and thyroid hormone production. Exposure to low doses of DDT is universal and begins in utero. Therefore, we studied adrenal medulla growth and function in male Wistar rats exposed to low doses of DDT during prenatal and postnatal development until puberty and adulthood, as well as rats exposed to DDT since the first day of postnatal development. All the exposed rats demonstrated lowered epinephrine blood levels, gradually reducing with age. DDT was found to inhibit the synthesis of tyrosine hydroxylase and affect the mitochondrial apparatus of epinephrine-producing cells during puberty and even after maturation. Low-dose exposure to DDT from birth resulted in more pronounced changes in adrenomedullary cells and a more profound decrease (up to 50%) in epinephrine secretion in adult rats. Prenatal onset of exposure demonstrated a mild effect on epinephrine-producing function (30% reduction), but was associated with lower rate of adrenal medulla growth during maturation and 25% smaller adrenal medullar size in adult rats. All subjects exposed to low doses of DDT failed to develop adaptive changes and restore proper epinephrine production. These results indicate a dysmorphogenetic effect of prenatal exposure and disruption of secretory function of adrenal chromaffin cells by postnatal exposure to DDT.

Features of the expression of Fox-1 in rat’s thyroid after prenatal dexamethasone action

The purpose of the work was to establish the features of Fox-1 expression and distribution in the parenchyma of the thyroid gland of rats in the postnatal period of ontogeny in the norm and after intrauterine action of dexamethasone.Material and methods: thyroid gland of rats (162 animals) of the Wistar line at the age from 1 to 14 days of postnatal development. Experimentally, the animals were injected intrauterinely with a solution of dexamethasone at a dose of 0.05 ml at a dilution of 1:40 on the 18th day of the dated pregnancy. The material was examined using a set of methods of morphological studies (production of histological serial sections, survey microscopy, morphometry, immunohistochemistry and statistical processing).Results of the research. In the thyroid glands of neonatal prenatal dexamethasone, the parenchyma was well developed and consisted of hollow colloid-type follicles and single colloid-type microfollicles, and a bright cytoplasmic reaction with Fox-1 antibodies was observed throughout the organ parenchyma. In the thyroid glands of animals of the 3rd day of life, morphological changes occurred in all groups of the experiment. In animals of the experimental group, hollow follicles of colloidal type of small, medium and large diameter were chaotically visualized throughout the body, and large follicles of irregular shape with immunohistochemical weak or negative reaction with Fox-1 antibodies in thyrocytes and lumen without colloidal evidence, which detected a decrease in the specific synthetic activity in these thyrocytes. On day 7 in the experimental group in the flattened thyrocytes of overstretched follicles, the expression of Fox-1 was present only in the apical part. On days 11-14 of postnatal development in the thyroid glands of rats experimentally prenatally exposed to dexamethasone in the wall of large follicles with flattened epithelium began extrafollicular proliferation of thyrocytes on the background of visualization in the lumen of these follicles desquamated cells. Intensive perinuclear and cytoplasmic Fox-1 positive reaction was present in extrafollicular proliferating thyrocytes.Conclusions. 1. The detected changes in the first day of life in the thyroid gland of rats indicated that prenatal administration of dexamethasone affects the intensification of differentiation not only structural and functional units - follicles, but also a specific synthetic intracellular apparatus of thyrocytes, judging by the intensification of Fox-1. Thus, immature pre-mRNA is converted into mature mRNA, from which thyroid proteins, in particular thyroglobulin, are translated. By the time of birth, this process in the experimental group reaches a significant development, covering the entire parenchyma of the gland. 2. In rats prenatally receiving dexamethasone, the period of lactation was characterized by intense structural changes in the thyroid gland, in particular intracellularly in thyrocytes of monolayer flattened epithelium, the expression of Fox-1 antibodies was sharply reduced, which was then replaced by a bright cytoplasmic reaction in proliferative clusters and follicles of colloidal type of secretion, which is an adaptive-compensatory mechanism of intracellular enhancement of proliferation of synthesizing organelles in response to the restructuring of a significant number of existing follicles by hypofunctional type, aimed at maintaining normal levels of thyroid function.

Age-Related Changes in the Ruminal Microbiota and Their Relationship With Rumen Fermentation in Lambs.

The rumen microbiota is vital for the health and growth performance of the host animal, mainly due to its role in the fermentation of ingested feed within the rumen. Attaining a better understanding of the development of the bacterial community and fermentation in the rumen can provide the theoretical basis for regulating feed utilization. This study analyzed the development of rumen bacteria in lambs from birth to 4 months of age using 16S-rRNA amplicon sequencing data and studied its relationship with ruminal fermentation. Serum levels of metabolites were monitored at 30, 60, 90, and 120 days of age, and the RandomForest approach was used to determine age-related changes in rumen bacteria. Levels of blood metabolites, ruminal fermentation, the rumen bacterial community and its functions were all affected by the age of the lambs (P < 0.05). Based on the Bray-Curtis distance within the age groups of the rumen microbiota, the similarity increased sharply after the lambs were weaned at 60 days of age (P < 0.05). The similarity between the samples collected from birth to 90 days of age and those collected at 120 days of age, increased after 20 days of age, reaching a maximum at 90 days vs. 120 days (P < 0.05). Some age-associated changes in the microbial genera were correlated with changes in the concentrations of volatile fatty acids and the levels of microbial crude protein in the rumen, including positive correlations between main volatile fatty acids and the genera of Prevotella 1, Lachnospiraceae NK3A20 group, Ruminococcus gauvreauii group, Ruminococcaceae UCG-014, and Ruminococcus 2 (P < 0.05). These results indicated that the microbial community and the function of rumen was not well-established before 20 days of age, so there is a degree of plasticity in the rumen bacterial community during the first 20 days of post-natal development in lambs, and this might provide an opportunity for interventions to improve rumen fermentation and, thus, increase their growth performance.

THE FOLLICLEGENESIS IN THE THYROID GLAND IN THE POSTNATAL PERIOD OF ONTOGENESIS UNDER PRENATAL ANTIGENIC INFLUENCE

Antigenic influence at critical terms of ontogenesis can cause significant changes in the child's immune system. It is known that the entry of antigens into the fetus causes premature release of T-lymphocytes from the thymus and their migration to various organs. The paper was aimed at the study of the folliclegenesis of the thyroid gland in postnatal period at norm and after prenatal influence of staphylococcal toxoid. In the experimental research as a material were thyroid glands of Wistar rats aged 1 to 60 days of postnatal development (162 animals), about 6 animals in each group. Three animals groups were studied on 1, 3, 7, 11, 14, 21, 30, 45, 60 days after bith. I gr. - intact animals (norm); ІІ gr. - control, animals which were injected intrauterine 0.9% NaCl solution; III - experimental animals injected with staphylococcal toxoid liquid purified adsorbed (10-14 units of binding in 1 ml, diluted 10 portions) by operation intrauterinely on the 18th day of dated pregnancy. Histological sections 3-5 μm thick were stained by hematoxylin and eosin, histochemicaly by alcian blue and azan staining. Immunohistochemical study was performed according to the protocol recommended for a particular antibody of the manufacturer. Used ki-67 (Ki-67), TTF-1 (8G7G3/1), Fox-1 (A-12) monoclonal antibodies by Santa Cruz Biotechnology, Inc. A set of morphometric studies was performed by microscope Carl Zeiss Primo Star equipped with the Axiocam digital microphoto attachment with using program complex Zeiss Zen 2011. The results were considered reliable at p≤0,05. For processing of statistical material was used the standard software package Microsoft Office Excel and Statistica 10.0.The results were obtained about morphogenesis of rat’s thyroid after intrauterine antigenic action of staphylococcal toxoid. Morphofunctional homeostasis and stromal-parenchymal proportional relationship to thyroid gland closely associated with the activity of immune cells, including special role of lymphocytes, macrophages, and mast cells. Prenatal influence of staphylococcal toxoid led to the formation of a more pronounced structure of the parenchyma and stroma, but they showed signs of functional immaturity after birth. During the sucking period, the simultaneous presence of intra-, extrafollicular, septal and intramural types of folliculogesis is determined, which is a local reaction to systemic antigenic irritation with activation of compensatory-adaptive reactive folliclegenesis. The revealed changes in the process of folliclegenesis, accompanied by venous plethora, the formation of intraorgan diffuse lymphoid tissue and nodules, desquamation of the follicular epithelium, redistribution of the follicle diameter is a reaction to the systemic antigenic effect on the body during the critical period of prenatal development and normalizes by 45 days.Keywords: morphogenesis, thyroid gland, antigen, staphylococcal toxoid, experiment.

Ультраструктурні зміни пінеальних клітин епіфіза за умов тривалої дії нітратів питної води та засобів корекції

According to modern data, the epiphyse (pineal gland) is an organ that combines the processes of adaptogenesis and immunogenesis, takes part in triggering stress reactions and determines the sequence of disorders in the body at different stages of stress development. Researchers consider the pineal gland to be the most important organizer of biological rhythms associated with photoperiodism and the organ that determines the stereotype of the organism. Its individual functions are rhythmically variable under the influence of the environment and age. The purpose of the study was to study the structural and functional changes of pineal cells of the pineal gland in rats at different stages of normal development, under the action of nitrates and the simultaneous action of nitrates and methylene blue. Materials and methods. In accordance with the purpose of the work, the study was carried out on 90 nonlinear white male rats of different ages. The animals were kept in the vivarium in equivalent conditions. Long-term exposure to nitrates on the body of animals was achieved by daily introduction into the drinking ration, starting from the 7th day of postnatal development of rats (after preliminary water purification), 120 mg/l sodium nitrate, that is, in a dose that is typical for many regions of Ukraine. When simulating the action of methylene blue, this substance was daily orally administered to the animals in doses: 0.1-0.15 ml of a 1% aqueous solution per 1 kg of body weight. Results and discussion. As a result of the 7-day action of nitrates in 14-day-old rats, structural changes were observed in the pineal gland, which corresponded to a decrease in the function of light cells and an increase in the functional activity of type II pinealocytes. The ultrastructure of the cytoplasm of type I pinealocytes contained poorly developed organelles and single secretory granules. In 45-day-old animals exposed to nitrates in light pinealocytes, pronounced disturbances in membrane organelles, primarily in mitochondria and the granular endoplasmic reticulum, were noted. The functional activity of dark pinealocytes increased during this period of the study. In the pineal parenchyma of 90-day-old rats after exposure to nitrates, the functional activity of type I pinealocytes was at a low level. The functional activity of dark pinealocytes was also weakened. Thus, as a result of the simultaneous action of nitrates and methylene blue in the pineal gland of 14-day-old rats, a tendency to gradual restoration of the structural and functional parameters of cells was observed. In 45-day-old animals, after the simultaneous action of nitrates and methylene blue, the ultrastructural data of pineal cells indicated numerous mitochondria and secretory granules in the cytoplasm. In the parenchyma of the pineal gland of 90-day-old rats after chronic action of nitrates and methylene blue at the ultrastructural level, no sharp changes in the cytoplasm and nucleus of light and dark pinealocytes were found in comparison with the control. Conclusion. The intake of nitrates in 14-day-old rats causes the development of a stress reaction, poorly developed organelles and signs of degranulation appear in the ultrastructure of light pinealocytes, however, the cytoplasm and nuclei of dark cells indicated an increase in function. In 45-day-old rats after exposure to nitrates, the signs of the stress reaction are enhanced. In the ultrastructure of the cytoplasm of light cells, pronounced violations of membrane organelles are determined. Enhanced function continues in dark pinealocytes. After the action of nitrates in 90-day-old rats, changes occur that are characteristic of the stage of depletion of the general adaptation syndrome, the result of which is a deep imbalance in the work of the pineal gland. The combined action of nitrates and methylene blue in 14-day-old animals helps to reduce the toxic effect and the strength of stress reactions in the pineal gland. In the ultrastructure of pinealocytes, the number of ribosomes, small secretory granules and mitochondria increases in comparison with the action of nitrates alone. In 45-day-old animals with the simultaneous intake of nitrates and methylene blue in the ultrastructure of melanotropic cells, the accumulation of secretory granules of the same size and electron density, an increase in the number of organelles and signs of restoration of the structure of the cytoplasm and nucleus are noted. The use of methylene blue against the background of long-term intake of nitrates in 90-day-old rats at the ultrastructural level of abrupt changes in the cytoplasm and nucleus of light and dark pinealocytes is not manifested in comparison with the control

Dynamics of distribution and structural-functional features of mast cells in the thyroid gland of rat's offspring in the norm and after penatal exposue of staphylococcal toxoid

The quantitative and functional state of mast cells, features of their localization in the age aspect of the early postnatal period of ontogenesis in normal and after prenatal exposure of staphylococcal toxoid to the fetus were studied in the thyroid gland of rats. As a material of the study were thyroid glands of Wistar rats aged 3 to 30 days of postnatal development (108 animals). Three groups of animals on the 3rd, 7th, 11th, 14th, 21st, 30th days of the postnatal life period were studied: I group – intact animals (norm); ІІ group – control, animals which were injected with 0.9% NaCl solution on the 18th day of the dated pregnancy; III group – experimental animals injected with staphylococcal toxoid liquid purified adsorbed (10-14 binding units in 1 ml, diluted 10 times) at a dose of 0.05 ml. Staphylococcal toxoid and 0.9% NaCl solution were administered to the fetus surgically during laparotomy, by intrauterine, transdermal subcutaneous injection into the interscapular area at a dose of 0.05 ml to each fetus. It is established that as a result of prenatal action of antigen-staphylococcal toxoid on the body postnatally in the early stages of development in the thyroid gland there is a balance between the processes of migration, distribution, degranulation of mast cells and proliferative processes of parenchyma, gland stroma and lymph node formation. In the thyroid gland during morphogenetic processes with the appearance of new follicles and intracellular regeneration, the population of mast cells responds with active degranulation, with the release into the intercellular space of biologically active substances, which apparently have a modulating effect on thyroid components and supporting the thyroid gland. recovery processes. Keywords: thyroid gland, antigen, staphylococcal toxoid, mast cells, experiment, rats.

Immunohistochemical features of expression and distribution of antibodies to thyroglobulin in the thyroid glands of newborn rats after prenatal exposure of dexamethasone

In clinical practice, synthetic glucocorticoids, such as dexamethasone, are used to accelerate fetal maturation in pregnant women at risk of preterm birth. Increasing the concentration of cortisol in humans and other mammals often causes structural and functional changes in fetal tissues, preparing it for childbirth and extrauterine life, but they can have long-term consequences in the structural organization of organs postnatally. Despite the large number of studies on the effect of glucocorticoids on the fetus, there are almost no data on the prenatal effect of dexamethasone on the processes of synthesis and resorption of thyroglobulin by thyroid thyrocytes in the postnatal period of life. Therefore, the aim of the study was to determine the immunohistochemical features of expression and distribution of antibodies to thyroglobulin in the thyroid glands of newborn rats in normal and after prenatal exposure to dexamethasone. The study material was the thyroid gland of Wistar rats aged 1 to 7 days of postnatal development (54 animals): I group - intact animals (norm); ІІ group - control, animals which were injected with 0.9% NaCl solution at a dose of 0.05 ml to each fetus on the 18th day of dated pregnancy; III group - experimental animals, which were administered a solution of dexamethasone at a dilution of 1:40 at a dose of 0.05 ml to each fetus on the 18th day of the date of pregnancy operatively during laparotomy, by intrauterine, transdermal subcutaneous injection into the interscapular area (Ukrainian patent №112288). Thyroglobulin Antibody (2H11) monoclonal antibodies: sc-51708 from Santa Cruz Biotechnology, Inc. were used for immunohistochemical study. Photo documentation of the studied objects was performed using a “Primo Star” microscope (Carl Zeiss, Germany) using an AxioCam camera using the Zeiss Zen program (2011). Analysis of micropreparations of thyroid glands of intact and control rats showed invariance of thyroglobulin synthesis and its accumulation, which was expressed by sufficient immunohistochemical expression of antibodies to thyroglobulin (ТgAb+). Prenatal administration of dexamethasone leads to intensification of the processes of morphological development of hormone-producing structures (follicles and follicular epithelium), production, resorption and iodination of thyroglobulin. This is evidenced by immunohistochemical studies found in 1-3 days of the neonatal period. It should be noted that on the 7th day of life the newborn was found intense changes in the structure of the parenchyma of the thyroid gland of animals of the experimental group: increased relative percentage of follicle cavity due to increased number of large and medium, some follicles had no resorption vacuoles which was accompanied by a slowdown in the excretion of hormones into the bloodstream and led to overstretching of the follicles and, as a consequence, to the flattening of the thyroid epithelium. Intrauterine administration of dexamethasone leads to prenatal acceleration of structure formation, folliculogenesis and enhancement of hormone-producing function, which is confirmed by the peculiarities of immunohistochemical expression of TgAb. By the end of the neonatal period in rats prenatally exposed to dexamethasone, the thyroid gland is depleted of compensatory-reactive internal reserves, which is morphologically and immunohistochemically manifested by signs of hypofunction and hypertrophy. Thus, detected in the thyroid glands of animals prenatally exposed to dexamethasone, aberration of cytoplasmic expression of ТgAb+, intensification of colloidal expression of ТgAb+, flattening of thyroid epithelium, and the absence of resorption vacuoles are signs of impaired hormone-forming function, which is the morphological basis for the development of hypofunctional states and requires further study.

Morphogenesis of the thyroid gland of rats of the early period after the prenatal action of Dexamethasone

Annotation. The aim of the study was to establish the features of the morphogenesis of the thyroid gland of rats at an early age of normal postnatal ontogenesis and after prenatal exposure to dexamethasone. The study material was the thyroid gland of rats (54 animals) of the Wistar line at the age of 1 to 14 days of postnatal development, which experimentally operatively, through the membrane, intrauterinely injected a solution of dexamethasone at a dose of 0.05 ml at a dilution of 1:40 on the 18th day of pregnancy; control group – 0.05 ml of 0.9% NaCl. Sections were stained with haematoxylin and eosin, azan, immunohistochemically (ki-67). Statistically used Student's parametric t-test, the normality of the distribution was checked using the Shapiro-Wilk test, the reliability is not less than 95%, the reliability at p&lt;0.05. In animals experimentally prenatally exposed to dexamethasone for 1-3 days, the gland was more functionally excited: the number of resorption vacuoles in the colloid, which was dense, increased, but the height of thyrocytes was almost no different from the control. There were more colloid-type follicles with ki-67-positive cells. On the 7th day of postnatal life, the structure of the gland changed in the direction of increasing the manifestations of the process of blocking the excretion of thyroid hormones, but the synthesis and excretion of components into the follicle cavity was preserved. Follicles increased throughout the body. On the 11th day of postnatal life in the thyroid glands of animals prenatally exposed to dexamethasone, the number of microfollicles decreased, and the proportion of proliferating ki-67-positive cells in the follicle wall decreased insignificantly compared to the previous period, but compared to the control of proliferating cells was less than 1.8 times. On 14th day, the thyroid gland of experimental animals was characterized by a mosaic arrangement of large follicles with flattened thyrocytes. Thus, the morphogenesis of the thyroid gland by hypofunctional type after prenatal exposure to dexamethasone in young rats indicates an adaptogenic compensatory response and morpho-functional immaturity of the organ during this period, which may be the basis for provoking the preservation of such morphogenetic factors under the influence of stressors.

Prenatal exposure to alcohol alters TLR4 signaling in the prefrontal cortex in rats

Prenatal alcohol exposure (PAE) can lead to developmental disorders of the central nervous system (CNS) and mental retardation. Toll-like receptor (TLR) 4 plays an important role in the development of defects in the nervous system caused by PAE. However, how PAE affects the TLR4 response in the brain remains unclear. Using the model of semi-forced alcoholization of pregnant rats, we investigated TLR4-mediated signaling on the 30th day of postnatal development in their offspring. Rats exposed to PAE showed a higher expression of proinflammatory cytokines in the prefrontal cortex, but TLR4-mediated signaling in response to lipopolysaccharide (LPS) was weakened. These data suggest that PAE can lead to neuroinflammation and suppression of the TLR4-mediated response to LPS in the prefrontal cortex of young rats. Since innate immunity plays an important role in brain development, PAE-induced suppression of the TLR4-mediated response may be one of the mechanisms for the development of CNS pathology.

Impaired postnatal development of the hippocampus of Krushinsky-Molodkina rats genetically prone to audiogenic seizures

The hippocampus plays an important role in epilepsy progression even if it is not involved in seizure generalization. We hypothesized that abnormal development of the hippocampus may underlie epileptogenesis. Here we analyzed postnatal development of the hippocampus of Krushinsky-Molodkina (KM) rats, which are the animal model of reflex audiogenic epilepsy. KM rats are genetically prone to audiogenic seizures that are expressed in age-dependent manner. The study was performed on seizure-naïve KM rats at several days of postnatal development (P15, P30, P60, P120). Wistar rats of the corresponding ages were used as a control. We showed that at early stages (P15, P30), the hippocampus of KM rats was characterized by significantly smaller cell population, but the number of proliferated cells was increased in comparison with control Wistar rats. Only at P60 proliferation and the total number of the hippocampal cells reached a level equal to Wistar rats. These data suggest delayed postnatal development of the hippocampus of KM rats. Analysis of apoptosis demonstrated significantly increased number of TUNEL-positive cells in the dentate gyrus (DG) of KM rats at P30 that was accompanied with expression of p53, Bcl-2 and cleaved caspases 3 and 9. Additionally, at all analyzed stages in the hilus of KM rats, the number of new-born glutamatergic cells was significantly increased that suggests formation of hilar ectopic granular cells. Our data suggest that in the case of hereditary epilepsy aberrant neurogenesis may be genetically determined.

Morphofunctional pecularrities and sialoglicans in lungs from offspring born from female rats with thyroid gland hyperfunction

Background. Over the last decade, there has been a global pending to increase the incidence of chronic obstructive pulmonary disease by 25% in men and 69% in women. Objective. To study the role of sialoglycans according to wheat germ lectin receptors (WGA) and morphofunctional features of offspring rats, which developed in conditions of hyperfunction of the thyroid gland of the maternal organism. Methods. The experimental study was performed on the offsprings of 20 females (10 control, 10 experimental) rats of the Wistar line. For 20 days before coupling the females of the experimental group received the drug L-thyroxine (Berlin-Chemie) at a dose of 150 μg / kg body weight. After euthanasia by overdose of ether anesthesia, the offspring from control and experimental females were taken lungs on the 1st, 10th, 20th and 40th day of postnatal development. Histological material was fixed in 4% neutral formalin, compacted and poured into paraffin blocks, made sections 5-7 μm thick. Review preparations were stained with hematoxylin and eosin according to standard methods. Wheat germ lectin WGA (Triticum vulgare) labeled with peroxidase-specific DGlcNAc NeuNAc was used to detect sialoglycans. Results. On the 1-40th day of postnatal development, the lungs of rats of the intact group show up typical morphology characteristic of rat lungs. On the tenth day of postnatal development in the offsprings lungs from females receiving L-thyroxine visually increases the number of alveoli, indicating an intensification of morphogenesis of lung tissue. Lectinohistochemical studies showed that on the first day of postnatal development in the lungs of rats of the intact group, receptors for sialospecific lectin WGA were identified on the surface of ciliated cells of the bronchial tree and vascular endothelium, while in the experimental group receptors for this lectin were found significantly in alveolar macrophages, visualised more often than in the lungs of the offspring from rats of the control group. Whereas on the 20th-40th day of postnatal development the number of macrophages with the presence of sialoglycans decreased. Conclusion. Studies have shown that in the lungs of offsprings from females receiving L-thyroxine, there are processes of intensification of the structural components of the lungs and the appearance of alveolar macrophages with the presence of sialospecific lectin WGA receptors, the number of which decreases during postnatal ontogenesi, that indicating a decrease of the immunity.

Influence of lead intoxication on morphological state of placenta-fertility system in rats in experiment

Topicality. Currently, one of the urgent issues of the analysis of environmental pollution is the presence of lead compounds with toxic effect on the functional systems of the human body. Regarding the literature data, lead compounds cause morphofunctional changes primarily in pregnant women’s placenta, leed to various disorders in physiological development of the fetus. Therefore, studies of exogenous effect of lead on the reproductive system of the body is a relevant and timely aspect in predicting and preventing its possible effect on pregnancy and the physiological development of the newborn.Aim. To study the effect of lead to morphological changes in the hematoplacental barrier of rats, morphological disorders of liver and kidney tissues in early postnatal ontogenesis.Materials and methods. An experimental study has been conducted on 30 female rats of weight 200-250 g and 70 rats on the 2-d, 17th, 30th, 40th day of postnatal development. The first group of rats included 10 females with physiological pregnancy. The second group consisted of 20 females who received daily oral lead acetic acid at a dose of 50 mg/kg body weight.Results and discussion. The electron microscopic results of experimental studies showed a violation of the compensatory mechanisms of the blood-brain barrier after daily gain of lead acetic acid. Newborn rats obtained by a physiologically healthy pregnancy have in the liver tissues was observed a rearrangement of the embryonic structure, the absence of a lobular and beam structure, a large number of cellular mitoses in the nuclei of hepatocytes. In all the study groups revealed circulatory disorders which manifested in the form of plethora of capillaries, portal and central veins. Erythrocyte hemolysis and areas of marked lymphohistiocytic infiltration of the connective tissue portal tracts were observed.Conclusions. According to the results of the study, it has been found the introduction of lead acetic acid at a dose of 50 mg/kg per day to pregnant rats adduced to dystrophic and discirculatory disorders in liver and kidneys of their offspring in postnatal ontogenesis, proved the consequence of lead toxicological poisoning.

The effects of metformin treatment on the ovaries and uterus of offspring

Objective The aim of this study is to investigate the effects of metformin treatment at different dosage levels on the ovaries and uteruses of rat offspring in the course of the intrauterine period. Methods Saline, metformin (100 mg/kg/day), and metformin (200 mg/kg/day) were administered via oral gavage between the 6th and 15th days of gestation to the 9 pregnant rats (n = 3/group). After birth, 5 female offspring were separated from each group and perfused on the 60th day of postnatal development. The cortex and medulla volumes of the ovaries, the thicknesses of epithelium and endometrium of the uteruses and the total oocyte number density were estimated. In addition, the estradiol levels in blood samples were measured by the ELISA method. Results There were no statistically significant differences among the groups regarding the number of oocytes, the volumes of ovarian cortex, medulla, primary and secondary follicles (p > .05). In comparison with the control group, the volume of the tertiary follicle, the thickness of the uterus epithelium, and the estradiol level were significantly decreased in Metformin 200 group (p < .05). Conclusions The gestational exposure to high dose metformin may result in decreased estradiol production and subsequently decreased endometrial thickness of offspring rats.

Risperidone accelerates bone loss in rats with autistic-like deficits induced by maternal lipopolysaccharides exposure

AimsPatients with neurodevelopmental disorders, usually suffer from bone diseases. Many studies have revealed a higher risk of fracture after atypical antipsychotic drug Risperidone (RIS) treatment, which is usually used to treat such disorders. It remains debatable whether neurodevelopmental disorders by itself are the cause of bone diseases or pharmacotherapy may be the reason. Materials and methodsThis study attempts to evaluate the biomechanical, histological, stereological, and molecular properties of bones in the offspring of Lipopolysaccharide (LPS) and saline-treated mothers that received saline, drug vehicle or the atypical antipsychotic drug risperidone (RIS) at different days of postnatal development. After postnatal drug treatment, animals were assessed for autistic-like behaviors. Then their bones were taken for evaluations. ResultsMaternal LPS exposure resulted in deficits in all behavioral tests and RIS ameliorated these behaviors (p < 0.01& p < 0.05). The administration of LPS and RIS individually led to a significant decrease in the biomechanical parameters such as bone stiffness, strength and the energy used to fracture of bone. The numerical density of osteocalcin-positive cells were significantly decreased in these groups. These rats also had decreased RUNX2 and osteocalcin gene expression. When LPS rats were treated with RIS, these conditions were accelerated (p < 0.001). DiscussionsThe results of our preclinical study, consistent with previous studies in animals, explore that autistic-like deficits induced by prenatal exposure to LPS, can reduce bone stability and bone mass similar to those observed in neurodevelopmental disorders, and, for the first time, reveal that this condition worsened when these animals were treated with RIS.