Early Stages Of Embryogenesis Research Articles

Inflammation of the Embryonic Choroid Plexus Barrier following Maternal Immune Activation.

The choroid plexus (ChP) regulates brain development by secreting instructive cues and providing a protective brain barrier. Here, we show that polyI:C-mediated maternal immune activation leads to an inflammatory response in the developing embryonic mouse brain that manifests as pro-inflammatory cerebrospinal fluid (CSF) and accumulation of ChP macrophages. Elevation of CSF-CCL2 was sufficient to drive ChP immune cell recruitment, activation, and proliferation. In addition, ChP macrophages abandoned their regular tiling pattern and relocated to the ChP-free margin where they breached the weakened epithelial barrier. We further found that these immune cells entered from the ChP into the brain via anatomically specialized "hotspots" at the distal tips of ChP villi. Invivo two-photon imaging demonstrated that surveillance behaviors in ChP macrophages had already emerged at this early stage of embryogenesis. Thus, the embryonic ChP forms a functional brain barrier that can mount an inflammatory response to external insults.

PGAP6, a GPI-specific phospholipase A2, has narrow substrate specificity against GPI-anchored proteins

PGAP6, also known as TMEM8A, is a phospholipase A2 with specificity to glycosylphosphatidylinositol (GPI) and expressed on the surface of various cells. CRIPTO, a GPI-anchored co-receptor for a morphogenic factor Nodal, is a sensitive substrate of PGAP6. PGAP6-mediated shedding of CRIPTO plays a critical role in an early stage of embryogenesis. In contrast, CRYPTIC, a close family member of CRIPTO, is resistant to PGAP6. In this report, chimeras between CRIPTO and CRYPTIC and truncate mutants of PGAP6 were used to demonstrate that the Cripto-1/FRL1/Cryptic domain of CRIPTO is recognized by an N-terminal domain of PGAP6 for processing. We also report that among 56 human GPI-anchored proteins tested, only glypican 3, prostasin, SPACA4, and contactin-1, in addition to CRIPTO, are sensitive to PGAP6, indicating that PGAP6 has a narrow specificity toward various GPI-anchored proteins.

Naked Poly(amidoamine) Dendrimer Nanoparticles Exhibit Intrinsic Embryotoxicity During the Early Stages of Normal Development.

To investigate the impact of poly(amidoamine) dendrimers (PAMAMs) in the embryo, we explored the outcome of different generations (G₄ and G6) on the early stages of embryogenesis using the chicken embryo as a model. We also monitored their effect on angiogenesis in the chorioallantoic membrane (CAM). Our data revealed that cationic PAMAMs provoke substantial embryotoxicity, as they significantly induce death (up to 50%, p < 0 05) and inhibit angiogenesis of the CAM (up to 30%, p < 0 05) in a generation-dependent manner in comparison to controls and other types of PAMAMs (anionic and neutral). Moreover, cationic PAMAMs alter the expression of genes related to cell survival, cell cycle, proliferation, transcription factor, apoptosis, and angiogenesis, as shown by RT-PCR analysis. Our data suggest that PAMAM dendrimers exhibit intrinsic toxicity in embryos at the early stages and inhibits angiogenesis of the CAM. Thus, future studies are necessary to illustrate the exact mechanism of PAMAM dendrimers in embryotoxicity.

RET Receptor Tyrosine Kinase: Role in Neurodegeneration, Obesity, and Cancer.

Rearranged during transfection (RET) is the tyrosine kinase receptor that under normal circumstances interacts with ligand at the cell surface and mediates various essential roles in a variety of cellular processes such as proliferation, differentiation, survival, migration, and metabolism. RET plays a pivotal role in the development of both peripheral and central nervous systems. RET is expressed from early stages of embryogenesis and remains expressed throughout all life stages. Mutations either activating or inhibiting RET result in several aggressive diseases, namely cancer and Hirschsprung disease. However, the physiological ligand-dependent activation of RET receptor is important for the survival and maintenance of several neuronal populations, appetite, and weight gain control, thus providing an opportunity for the development of disease-modifying therapeutics against neurodegeneration and obesity. In this review, we describe the structure of RET, its signaling, and its role in both normal conditions as well as in several disorders. We highlight the differences in the signaling and outcomes of constitutive and ligand-induced RET activation. Finally, we review the data on recently developed small molecular weight RET agonists and their potential for the treatment of various diseases.

The Oncogenic Functions of Insulin-like Growth Factor 2 mRNA-Binding Protein 3 in Human Carcinomas.

IGF2BP3 (also known as IMP3, KOC), a member of the insulin-like growth factor mRNA-binding protein family (IMPs), has been a research target in recent studies of promoting embryo development and exacerbating cancer. IGF2BP3 is ubiquitously expressed in early embryogenesis stages but limited in postembryonic stages, which is important in many physiological aspects such as stem cell renewal, morphological development and metabolism. A large number of studies show that IGF2BP3 interacts with many kinds of non-coding RNAs and proteins to promote cancer cell proliferation and metastasis and inhibit cancer cell apoptosis. As IGF2BP3 is highly expressed in advanced cancers and associated with poor overall survival rates of patients, it may be a potential molecular marker in cancer diagnosis for the detection of cancerous tissues and an indicator of cancer stages. Therefore, anti-IGF2BP3 drugs or monoclonal antibodies are expected as new therapeutic methods in cancer treatment. This review summarizes recent findings among IGF2BP3, RNA and proteins in cancer processes, with a focus on its cancer-promoting mechanisms and potential application as a new biomarker for cancer diagnosis and treatment.

Posttranscriptional regulation of maternal Pou5f1/Oct4 during mouse oogenesis and early embryogenesis.

Protein syntheses at appropriate timings are important for promoting diverse biological processes and are controlled at the levels of transcription and translation. Pou5f1/Oct4 is a transcription factor that is essential for vertebrate embryonic development. However, the precise timings when the mRNA and protein of Pou5f1/Oct4 are expressed during oogenesis and early stages of embryogenesis remain unclear. We analyzed the expression patterns of mRNA and protein of Pou5f1/Oct4 in mouse oocytes and embryos by using a highly sensitive in situ hybridization method and a monoclonal antibody specific to Pou5f1/Oct4, respectively. Pou5f1/Oct4 mRNA was detected in growing oocytes from the primary follicle stage to the fully grown GV stage during oogenesis. In contrast, Pou5f1/Oct4 protein was undetectable during oogenesis, oocyte maturation and the first cleavage stage but subsequently became detectable in the nuclei of early 2-cell-stage embryos. Pou5f1/Oct4 protein at this stage was synthesized from maternal mRNAs stored in oocytes. The amount of Pou5f1/Oct4 mRNA in the polysomal fraction was small in GV-stage oocytes but was significantly increased in fertilized eggs. Taken together, our results indicate that the synthesis of Pou5f1/Oct4 protein during oogenesis and early stages of embryogenesis is controlled at the level of translation and suggest that precise control of the amount of this protein by translational regulation is important for oocyte development and early embryonic development.

Dynamic pattern of histone H3 core acetylation in human early embryos

ABSTRACT After fertilization, highly differentiated sperm and oocyte are reprogrammed to totipotent embryo, which subsequently cleavages and develops into an individual through spatial-temporal differentiation. Histone modifications play critical roles to coordinate with other reprogramming events in early stages of embryogenesis. However, most of studies focus on modifications at N-terminus of histones, those at nucleosome core were not well understood. Here, we characterize the three key acetylation events in the histone H3 core, H3K56/K64/K122ac, in early human embryos. The three residues localize at DNA entry-exit position of the nucleosome. Globally, H3K56ac, H3K64ac and H3K122ac were detectable throughout preimplantation stages, with H3K64ac levels being relatively stronger and H3K122ac levels being much weaker. Besides, H3K56ac level had a peak at two-cell stage. Moreover, we found that LINEs also peak at two-cell stage, and H3K56ac was enriched at young LINE-1 in human ESCs, supporting that H3K56ac is an important driving force for young LINE-1 activation in human preimplantation embryos. Our results suggest that acetylation in the nucleosome core of histone H3 is dynamic and various during preimplantation development, and may drive diverse chromatin remodeling events in this developmental window.

Heart malformation is an early response to valproic acid in developing zebrafish.

Valproic acid (VPA) is a branched short-chain fatty acid primarily used in epilepsy, but is also used in bipolar disorder, migraine, and psychotic disorders. Despite its wide range of use, it is a teratogen resulting in various congenital abnormalities. Although a large number of scientific studies evidenced the teratogenic effects, there are limited data on embryonic exposure to VPA at specific or different stages of early embryogenesis. Based on this, the present study was planned to investigate the embryonic exposure to VPA at specific and different hours post fertilization (hpf) in zebrafish embryonic model. In first set of experiments, embryos from spawning groups of adult zebrafish were exposed to different molar concentrations of VPA at 2.5 hpf, and in the second set of experiments, embryos were exposed to VPA 100μM at 24 hpf, 36 hpf, 48 hpf, 72 hpf, and 96 hpf. The parameters examined were hatching rate, mortality, morphology, body length, pericardial sac size, heartrate, anatomical changes in heart, skeletal and notochord till 120 hpf. It was observed that the embryos exposed to VPA at 2.5 hpf suffered from cardiac abnormalities including heart malformation, bradycardia, circulatory failure, and pericardial sac enlargement which was more apparent in embryos exposed to 100μM VPA. In the second set of experiments, embryos exposed to VPA 100μM at 24 hpf and 36 hpf suffered from heart malformations, but there was no incidence of cardiac malformation in embryos exposed to VPA at 48 hpf, 72 hpf, and 96hpf. From the results, it was evident that exposure to VPA at early developmental stage of embryogenesis produced congenital cardiac abnormalities. Since VPA is a selective HDAC inhibitor, histone acetylation with aberrant gene expression during cardiogenesis might be the underlying cause of cardiac malformation.

Significant Toxic Effect of Carbon Nanofibers at the Early Stage of Embryogenesis.

Implementation of carbon nanofibers (CNFs) in biomedical applications have successful outcomes, however, they are still considered as a potential hazard. We herein used avian embryos at 3 days and its chorioallantoic membrane (CAM) at 6 days of incubation to evaluate the impact of synthesized CNFs on the early stage of embryogenesis and angiogenesis. Our data point out that 50 μg/embryo concentration of CNFs provoke adverse effects as 75% of CNFs-exposed embryos die within 1-5 days after exposure compared with their matched controls. Furthermore, CNFs significantly inhibit angiogenesis of the CAM after 48-hours post-treatment. Additionally, RT-PCR analysis on seven key controller genes responsible for proliferation, survival, angiogenesis, and apoptosis showed that these genes are deregulated in brain, heart, and liver tissues of CNFs-exposed embryos compared to their matched control. Our investigation suggests that CNFs could have a toxic effect on the early stages of embryogenesis as well as angiogenesis. Nevertheless, further investigations are required to evaluate the effects of CNFs and elucidate their mechanism on the early stage of the normal development and human health.

E-Cigarette Liquid Provokes Significant Embryotoxicity and Inhibits Angiogenesis.

E-cigarette smoking (ECS) is a new method of tobacco smoking that is gaining popularity as it is thought to be a “healthy method” of tobacco consumption. The adverse outcomes of ECS on the respiratory and cardiovascular systems in humans have been recently demonstrated. Nevertheless, the effect of e-cigarette liquid (ECL) on the early stage of embryogenesis and angiogenesis has not been explored yet. Chicken embryo at 3 days of incubation and its chorioallantoic membrane (CAM) of 5 days were used to explore the outcome of ECL on the embryo. Real-time PCR was also employed to study the regulation of a set of key controller genes of embryogenesis as well as angiogenesis. Our study revealed that ECL exposure is associated with a high rate of mortality in embryos as around 70% of treated embryos, at 3 days of incubation, die after 5 days of exposure. Additionally, ECL inhibits angiogenesis of the CAM of 5 days of incubation by more than 30%. These effects could be explained by the upregulation of ATF-3, FOXA2, INHBA, MAPRE-2, and RIPK-1, as well as the downregulation of SERPINA-4 and VEGF-C genes, which are important key controller genes of embryogenesis as well as angiogenesis. Our data suggest clearly that ECS can have dramatic toxic outcomes on the early stage of embryogenesis as well as angiogenesis. Accordingly, we believe that further studies to assess the effects of ECS on human health are essential.

Transcriptome Analysis of the Oriental Fruit Fly Bactrocera dorsalis Early Embryos.

The oriental fruit fly, Bactrocera dorsalis (Hendel), is one of the most devastating and highly invasive agricultural pests world-wide, resulting in severe economic loss. Thus, it is of great interest to understand the transcriptional changes that occur during the activation of its zygotic genome at the early stages of embryonic development, especially the expression of genes involved in sex determination and the cellularization processes. In this study, we applied Illumina sequencing to identify B. dorsalis sex determination genes and early zygotic genes by analyzing transcripts from three early embryonic stages at 0–1, 2–4, and 5–8 h post-oviposition, which include the initiation of sex determination and cellularization. These tests generated 13,489 unigenes with an average length of 2185 bp. In total, 1683, 3201 and 3134 unigenes had significant changes in expression levels at times after oviposition including at 2–4 h versus 0–1 h, 5–8 h versus 0–1 h, and 5–8 h versus 2–4 h, respectively. Clusters of gene orthology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations were performed throughout embryonic development to better understand the functions of differentially expressed unigenes. We observed that the RNA binding and spliceosome pathways were highly enriched and overrepresented during the early stage of embryogenesis. Additionally, transcripts for 21 sex-determination and three cellularization genes were identified, and expression pattern analysis revealed that the majority of these genes were highly expressed during embryogenesis. This study is the first assembly performed for B. dorsalis based on Illumina next-generation sequencing technology during embryogenesis. Our data should contribute significantly to the fundamental understanding of sex determination and early embryogenesis in tephritid fruit flies, and provide gene promoter and effector gene candidates for transgenic pest-management strategies for these economically important species.

Reactive oxygen species signaling in primordial germ cell development in Drosophila embryos.

REDOX mechanisms that induce biosynthesis of the reactive oxygen species (ROS) have attracted considerable attention due to both the deleterious and beneficial responses elicited by the reactive radical. In several organisms including Drosophila melanogaster, modulation of ROS activity is thought to be crucial for the maintenance of cell fates in developmental contexts. Interestingly, REDOX mechanisms have been shown to be involved in maintaining progenitor fate of stem cells as well as their proliferation and differentiation. Here, we have explored the possible functions of ROS during proper specification and developmental progression of embryonic primordial germ cells (PGCs). Indicating its potential involvement in these processes, ROS can be detected in the embryonic PGCs and the surrounding somatic cells from very early stages of embryogenesis. Using both "loss" and "gain" of function mutations in two different components of the REDOX pathway, we show that ROS levels are likely to be critical in maintaining germ cell behavior, including their directed migration. Altering the activity of a putative regulator of ROS also adversely influences the ability of PGCs to adhere to one another in cellular blastoderm embryos, suggesting potential involvement of this pathway in orchestrating different phases of germ cell migration.

Development of Multiplexed Immuno-N-Terminomics to Reveal the Landscape of Proteolytic Processing in Early Embryogenesis of Drosophila melanogaster.

Protein expression levels are regulated through both translation and degradation mechanisms. Levels of degradation intermediates, that is, partially degraded proteins, cannot be distinguished from those of intact proteins by global proteomics analysis, which quantify total protein abundance levels. This study aimed to develop a tool for assessing the aspects of degradation regulation via proteolytic processing through a new multiplexed N-terminomics method involving selective isobaric labeling of protein N-termini and immunoaffinity capture of the labeled N-terminal peptides. Our method allows for not only identification of proteolytic cleavage sites, but also highly multiplexed quantification of proteolytic processing. We profiled a number of potential cleavage sites by signal peptidase and provided experimental confirmation of predicted cleavage sites of signal peptide. Furthermore, the present method uniquely represents the landscape of proteomic proteolytic processing rate during early embryogenesis in Drosophila melanogaster, revealing the underlying mechanism of stringent decay regulation of zygotically expressed proteins during early stages of embryogenesis.

MXene Nanosheets May Induce Toxic Effect on the Early Stage of Embryogenesis.

MXene (Ti₃C₂Tx), as a novel 2D material, has produced a great interest due to its promising properties in biomedical applications, nevertheless, there is a lack of studies dedicated to investigate the possible toxic effect of MXene in embryos. Herein, we aim to scrutinize the potential toxicity of MXene nanosheets on the early stage of the embryo as well as angiogenesis. Avian embryos at 3 and 5 days of incubation were used as an experimental model in this investigation. Our findings reveal that MXene may produce adverse effect on the early stage of embryogenesis as ∼46% of MXene-exposed embryos died during 1-5 days after exposure. We also found that MXene at tested concentration inhibits angiogenesis of the chorioallantoic membrane of the embryo after 5 days of incubation. More significantly, RT-PCR analysis of seven genes, which are key regulators of cell proliferation, survival, cell death and angiogenesis, revealed that these genes were deregulated in brain, heart and liver tissues from MXene-treated embryos in comparison with their matched controls. Our study clearly suggests that MXene at studied concentration might induce a toxic effect on the early stage of embryogenesis; nevertheless, more investigations are necessary to understand the effect at low concentrations and elucidate its mechanism at the early stage of normal development.

Expression analysis of glutathione S-transferases and ferritins during the embryogenesis of the tick Haemaphysalis longicornis

In the tick life cycle, embryogenesis is the only stage of development wherein no blood meal is required. Nevertheless, even in the absence of a blood meal, which is the source of nutrients as well as the ferrous iron and heme that could cause oxidative stress in ticks, malondialdehyde (MDA) has been reported to increase during this period. Additionally, the knockdown of some oxidative stress–related molecules such as ferritin has resulted in abnormal eggs and embryonic death.Here, we investigate the gene and protein expression profiles of the identified glutathione S-transferases (GSTs) and ferritins (Fers) of the tick H. longicornis during embryogenesis through quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blotting, respectively. We also confirm the lipid peroxidation and ferrous iron concentration level using a thiobarbituric acid reactive substances (TBARS) assay. Finally, we attempt to correlate these findings with the events occurring by establishing a staging process in H. longicornis embryos.Lipid peroxidation increased during the course of embryogenesis, as does the amount of GST proteins. On the other hand, the GST genes have high expression at the 1st day post-oviposition, during the early stage of embryogenesis and at day 10 during the period wherein the germ band is observable. Fer gene expression also starts to increase at day 10 and peaks at day 15. In the ferritin proteins, only the secretory ferritin (Fer2) is detected and constitutively expressed during embryogenesis.Events occurring during embryogenesis, such as energy production and iron metabolism for cellular proliferation and differentiation cause oxidative stress in the embryo. To counteract oxidative stress, it is possible that the embryo may utilize oxidative stress–related molecules such as GSTs and Fer2, which could be either maternally or embryo-derived.

The role of Hippo signaling pathway and mechanotransduction in tuning embryoid body formation and differentiation.

Embryoid bodies (EBs) are the three-dimensional aggregates of pluripotent stem cells that are used as a model system for the in vitro differentiation. EBs mimic the early stages of embryogenesis and are considered as a potential biomimetic body in tuning the stem cell fate. Although EBs have a spheroid shape, they are not formed accidentally by the agglomeration of cells; they are formed by the deliberate and programmed aggregation of stem cells in a complex topological and biophysical microstructure instead. EBs could be programmed to promisingly differentiate into the desired germ layers with specific cell lineages, in response to intra- and extra-biochemical and biomechanical signals. Hippo signaling and mechanotransduction are the key pathways in controlling the formation and differentiation of EBs. The activity of the Hippo pathway strongly relies on cell-cell junctions, cell polarity, cellular architecture, cellular metabolism, and mechanical cues in the surrounding microenvironment. Although the Hippo pathway was initially thought to limit the size of the organ by inhibiting the proliferation and the promotion of apoptosis, the evidence suggests that this pathway even regulates stem cell self-renewal and differentiation. Considering the abovementioned explanations, the present study investigated the interplay of the Hippo signaling pathway, mechanotransduction, differentiation, and proliferation pathways to draw the molecular network involved in the control of EBs fate. In addition, this study highlighted several neglected critical parameters regarding EB formation, in the interplay with the Hippo core component involved in the promising differentiation.

H3K27me3 suppresses sister-lineage somatic gene expression in late embryonic germline cells of the ascidian, Halocynthia roretzi

Protection of the germline from somatic differentiation programs is crucial for germ cell development. In many animals, whose germline development relies on the maternally inherited germ plasm, such protection in particular at early stages of embryogenesis is achieved by maternally localized global transcriptional repressors, such as PIE-1 of Caenorhabditis elegans, Pgc of Drosophila melanogaster and Pem of ascidians. However, zygotic gene expression starts in later germline cells eventually and mechanisms by which somatic gene expression is selectively kept under repression in the transcriptionally active cells are poorly understood.By using the ascidian species Halocynthia roretzi, we found that H3K27me3, a repressive transcription-related chromatin mark, became enriched in germline cells starting at the 64-cell stage when Pem protein level and its contribution to transcriptional repression decrease. Interestingly, inhibition of H3K27me3 together with Pem knockdown resulted in ectopic expression in germline cells of muscle developmental genes Muscle actin (MA4) and Snail, and of Clone 22 (which is expressed in all somatic but not germline cells), but not of other tissue-specific genes such as the notochord gene Brachyury, the nerve cord marker ETR-1 and a heart precursor gene Mesp, at the 110-cell stage. Importantly, these ectopically expressed genes are normally expressed in the germline sister cells (B7.5), the last somatic lineage separated from the germline. Also, the ectopic expression of MA4 was dependent on a maternally localized muscle determinant Macho-1. Taken together, we propose that H3K27me3 may be responsible for selective transcriptional repression for somatic genes in later germline cells in Halocynthia embryos and that the preferential repression of germline sister-lineage genes may be related to the mechanism of germline segregation in ascidian embryos, where the germline is segregated progressively by successive asymmetric cell divisions during cell cleavage stages. Together with findings from C. elegans and D. melanogaster, our data for this urochordate animal support the proposal for a mechanism, conserved widely throughout the animal kingdom, where germline transcriptional repression is mediated initially by maternally localized factors and subsequently by a chromatin-based mechanism.

Survival of Polyploid hybrid salamander embryos

BackgroundAnimals with polyploid, hybrid nuclei offer a challenge for models of gene expression and regulation during embryogenesis. To understand how such organisms proceed through development, we examined the timing and prevalence of mortality among embryos of unisexual salamanders in the genus Ambystoma.ResultsOur regional field surveys suggested that heightened rates of embryo mortality among unisexual salamanders begin in the earliest stages of embryogenesis. Although we expected elevated mortality after zygotic genome activation in the blastula stage, this is not what we found among embryos which we reared in the laboratory. Once embryos entered the first cleavage stage, we found no difference in mortality rates between unisexual salamanders and their bisexual hosts. Our results are consistent with previous studies showing high rates of unisexual mortality, but counter to reports that heightened embryo mortality continues throughout embryo development.ConclusionsPossible causes of embryonic mortality in early embryogenesis suggested by our results include abnormal maternal loading of RNA during meiosis and barriers to insemination. The surprising survival rates of embryos post-cleavage invites further study of how genes are regulated during development in such polyploid hybrid organisms.

CHRONONEONATOLOGY: BIORHYTHMIC ENTITY OF A NEWBORN

Human biorhythms display the adaptation of living organisms to the external environment. These are mechanisms that are so well-regulated by nature that they are often called ‘biological clock’.There are definite functions in the body of the newborn that have a daily rhythm (with a period of 2 to 25 hours). Such a rhythmic setup depends on the maturity of the newborn: the circadian rhythm of melatonin synthesis in humans arises from the first days after birth, and its formation ends up 9-12 weeks and in premature babies for 2-3 weeks later. The development of the ‘biological clock’ of the newborn is significantly influenced by the conditions of the environment. Melatonin provides recovery, stabilization and synchronization of chronorhythms of different frequencies, including daily periodism.At this rate, the pleiotropic effects of melatonin on the control of biological rhythms during this period are a matter of particular attention. Our reference is devoted to it.During early postnatal adaptation, it is reasonable to determine the biorhythmologic features of the main physiological indicators of life: hourly blood pressure, heart rate and respiratory movements, body temperature, cortisol, adrenaline, norepinephrine, 6-sulfatoxymelatonin (melatonin metabolite) in fractional urine in the dynamics of the early neonatal period.The tasks of chrononeonatology are the study of the peculiarities of the formation of the circadian setup of physiological functions and the level of the main adaptive hormones in the dynamics of the early neonatal period.In the prenatal period, melatonin penetrates the fetus from the pregnant woman through the placenta, and after birth it enters the baby's body with the mother's milk. It is believed that periodic signals emanating from the mother's pineal gland (PG) cells synchronize the fetal chronorhythms. In the early stages of embryogenesis, these signals have a nervous and humoral genesis, and after birth, only humoral influences.The concentration of melatonin in the blood of a pregnant woman reaches a maximum level to the 32nd week of pregnancy and is restored by the 2nd day after childbirth.Fetal growth restriction is due to a significant decrease in the secretion of melatonin during the first 3 months of life of newborns. It is important that in the preterm infants, the relative deficit of melatonin lasts from 2-4 to 7-8 months.Maternal influence on development does not end with delivery, but continues in the neonatal period. Breast milk contains more than 60 biologically active substances (STH, lactogenic hormone, IGF-1, insulin, etc., in particular melatonin), whose level significantly exceeds their concentration in the peripheral blood of the mother.Early breastfeeding, the rooming-in in the postpartum period, an arbitrary feeding regime contribute to the earlier formation of biorhythms of physiological indicators of life and the favorable course of adaptive processes in newborns.So, summing up, we note that the child's condition is associated with an adequate biorhythmic daily activity. Metabolism lability in the newborn requires keeping in mind the structure of biorhythms in the postnatal period to prevent the development of morbid conditions.

Clinical case of thromboembolism of small branches of the pulmonary artery on the background of the single ventricle id type with the opening of the сava-caval collaterals

A three-compartment heart - a severe congenital defect, can develop after genetic mutation or teratogenic influence on fetus at early stages of embryogenesis. According to the literary data, the survival of such patients without surgery is 6-7 %. This publication demonstrates clinical case of the patient who has single ventricle of the heart and lived up to 56 without surgery.