Autophagy as a Therapeutic Target of Natural Products Enhancing Embryo Implantation

Infertility is an emerging health issue worldwide, and female infertility is intimately associated with embryo implantation failure. Embryo implantation is an essential process during the initiation of prenatal development. Recent studies have strongly suggested that autophagy in the endometrium is the most important factor for successful embryo implantation. In addition, several studies have reported the effects of various natural products on infertility improvement via the regulation of embryo implantation, embryo quality, and endometrial receptivity. However, it is unclear whether natural products can improve embryo implantation ability by regulating endometrial autophagy. Therefore, we performed a literature review of studies on endometrial autophagy, embryo implantation, natural products, and female infertility. Based on the information from these studies, this review suggests a new treatment strategy for female infertility by proposing natural products that have been proven to be safe and effective as endometrial autophagy regulators; additionally, we provide a comprehensive understanding of the relationship between the regulation of endometrial autophagy by natural products and female infertility, with an emphasis on embryo implantation.

Features of Blood Supply to the Bones of the Lower Leg in the Ankle Joint Region

The purpose of the study was to investigate the topography of permeable (nutrition) arteries in the lower third of leg during human ontogenesis. Materials and methods. The research was conducted on 30 specimens of human prefetuses and fetuses aged 3-9 months of prenatal development; 28 bone specimens of adult tibia and fibula and 27 series of computerized tomography scans of lower extremities of adults aged 21-72 were used. We have used a complex of methods for morphological research: anthropometry, morphometry, macromicroscopy, injections of blood vessels of X-ray contrasting mixtures, three-dimensional reconstruction and statistical analysis. Results and discussion. Cartilage osteogenesis occurs in the prefetal period of prenatal human development, in which blood vessels play a crucial morphofunctional role. During endochondral ossification of the tibia, the vessels of the bone cuff grow into the diaphysis of the cartilaginous model of the bone and osteogenic cells go beyond their limits. In the third trimester of prenatal development, blood vessels grow into the epiphyseal part of the cartilaginous model and an epiphyseal centre of ossification forms. Between the epiphysis and diaphysis centers of ossification, a metaphysical growth plate forms that develops intraosseous anastomosis between the diaphyseal and metaphysical blood vessels. In the metaphysis region, there are extra-skeletal anastomoses. Often, the insertion of nutrition arteries into the bone of the tibia is usually the middle third of bones (55%) and distal metaphysis (37%). In 10%, there were nutrition foramina in the upper third of the tibia. Three-dimensional reconstruction also clearly shows a more extensive and developed network of vessels in the bone marrow canal in metaphysical regions. In the middle third of the tibia and fibula, 1-3 nutrient foramina can be traced on most specimens. On the fibular, in addition to the posterior-medial localization of the nutrient arteries, there were variants with a "high" (above the metaphysis) placement of the entrance of the vessel into the bone substance. Conclusion. The most common places where arteries enter the bones of the lower leg are the middle third of the bones (55%) and the distal metaphysis (37%). In 10%, there were nutrient foramina in the upper third of the tibia. The three-dimensional reconstruction also clearly shows a more extensive and developed network of vessels in the bone marrow canal in metaphysical regions. During the postnatal period, we most often encountered the localization of nutritional arteries on the anterior-lateral surface of the tibia (23%), or their combination – the presence of both nutrient arteries on the posterior and medial bone surfaces (18.3%)

The origins and functional effects of postzygotic mutations throughout the human lifespan

Postzygotic mutations (PZMs) begin to accrue in the human genome immediately after fertilization, but how and when PZMs affect development and lifetime health remains unclear. To study the origins and functional consequences of PZMs, we generated a multi-tissue atlas of PZMs from 948 donors using the final major release of the Genotype-Tissue Expression (GTEx) project. Nearly half the variation in mutation burden among tissue samples can be explained by measured technical and biological effects, while 9% can be attributed to donor-specific effects. Through phylogenetic reconstruction of PZMs, we find that their type and predicted functional impact varies during prenatal development, across tissues, and the germ cell lifecycle. Remarkably, a class of prenatal mutations was predicted to be more deleterious than any other category of genetic variation investigated and under positive selection as strong as somatic mutations in cancers. In total, the data indicate that PZMs can contribute to phenotypic variation throughout the human lifespan, and, to better understand the relationship between genotype and phenotype, we must broaden the long-held assumption of one genome per individual to multiple, dynamic genomes per individual.

Ectodysplasin A/Ectodysplasin A Receptor System and Their Roles in Multiple Diseases

Ectodysplasin A (EDA) is a member of the tumor necrosis factor (TNF) family of ligands that was initially reported to induce the formation of various ectodermal derivatives during normal prenatal development. EDA exerts its biological activity as two splice variants, namely, EDA-A1 and EDA-A2. The former binds to the EDA receptor (EDAR), resulting in the recruitment of the intracellular EDAR-associated death domain (EDARADD) adapter protein and the activation of the NF-κB signaling pathway, while the latter binds to a different receptor, EDA2R, also known as X-linked ectodermal dysplasia receptor (XEDAR). Inactivation mutation of the EDA gene or the genes coding for its receptors can result in hypohidrosis ectodermal dysplasia (HED), a condition that is characterized by oligotrichosis, edentulosis or oligodontia, and oligohidrosis or anhidrosis. Recently, as a new liver factor, EDA is gradually known and endowed with some new functions. EDA levels were observed to be upregulated in several metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD), obesity, and insulin resistance. In addition, EDA and its receptors have been implicated in tumor pathogenesis through the regulation of tumor cell proliferation, apoptosis, differentiation, and migration. Here, we first review the role of EDA and its two-receptor system in various signaling pathways and then discuss the physiological and pathological roles of EDA and its receptors.

Lingual means of the denotation in the Ukrainian language for age development periods of a child in the first year of the life

The names of age periods of the first year of a child’s life were considered in the paper. Traditionally the first year of a child’s life was not clearly divided into shorter stages, and in turn, there were no established names which would correlate with these age periods. In every-day life defining features for a child of the first year of life is the fact of birth itself, which fixes a noun-composite a newly-born, as well as expressive signs associated with feeding a baby and its (his/her) inability to speak, namely, such nouns as a nursling and a baby. A clearly differentiated division of a child’s age period, before reaching the age of one year, is recorded in medicine. Scientific observations of the physiological changes in the development of a child, depending on a lived calendar period, determined the classification of the life into certain stages beginning from the prenatal development; it was expressed in a special terminology, for example, a perinatal period, a zero day. In a medical sphere the division units of a life period before the age of one year are hours, days, months; thus, this temporal vocabulary belongs to the structure of terminological phrases used to denote a certain age stage, the gradation of periods can be done with help of adjectives-qualifiers early, late. In a pedagogical discourse, contrary to a medical sphere, the names of the age periods in a child’s life do not clearly correlate with physiological changes and a calendar duration, and in an every-day life discourse the correlation is seen the least. However a conversational speech is characterized with a larger number of the patterns which form the names of age periods, descriptive nominations, due to a child’s socialization. Thus, a set of nominative units is different for each discourse, but we can come across some scientific terms in mass media, and from there they can be found in a conversational speech. In a pedagogical, medical, every-day life discourse we have the cases when the same nouns are used, for instance, a newly-born, however they differ semantically.

Developmental Patterning and Neurogenetic Gradients of Nurr1 Positive Neurons in the Rat Claustrum and Lateral Cortex

The claustrum is an enigmatic brain structure thought to be important for conscious sensations. Recent studies have focused on gene expression patterns, connectivity, and function of the claustrum, but relatively little is known about its development. Interestingly, claustrum-enriched genes, including the previously identified marker Nurr1, are not only expressed in the classical claustrum complex, but also embedded within lateral neocortical regions in rodents. Recent studies suggest that Nurr1 positive neurons in the lateral cortex share a highly conserved genetic expression pattern with claustrum neurons. Thus, we focus on the developmental progression and birth dating pattern of the claustrum and Nurr1 positive neurons in the lateral cortex. We comprehensively investigate the expression of Nurr1 at various stages of development in the rat and find that Nurr1 expression first appears as an elongated line along the anterior-posterior axis on embryonic day 13.5 (E13.5) and then gradually differentiates into multiple sub-regions during prenatal development. Previous birth dating studies of the claustrum have led to conflicting results, therefore, we combine 5-ethynyl-2′-deoxyuridine (EdU) labeling with in situ hybridization for Nurr1 to study birth dating patterns. We find that most dorsal endopiriform (DEn) neurons are born on E13.5 to E14.5. Ventral claustrum (vCL) and dorsal claustrum (dCL) are mainly born on E14.5 to E15.5. Nurr1 positive cortical deep layer neurons (dLn) and superficial layer neurons (sLn) are mainly born on E14.5 to E15.5 and E15.5 to E17.5, respectively. Finally, we identify ventral to dorsal and posterior to anterior neurogenetic gradients within vCL and DEn. Thus, our findings suggest that claustrum and Nurr1 positive neurons in the lateral cortex are born sequentially over several days of embryonic development and contribute toward charting the complex developmental pattern of the claustrum in rodents.

Associations between indicators of socioeconomic position and DNA methylation: a scoping review

Background Socioeconomic position (SEP) is a major determinant of health across the life course. Yet, little is known about the biological mechanisms explaining this relationship. One possibility widely pursued in the scientific literature is that SEP becomes biologically embedded through epigenetic processes such as DNA methylation (DNAm), wherein the socioeconomic environment causes no alteration in the DNA sequence but modifies gene activity in ways that shape health. Methods To understand the evidence supporting a potential SEP-DNAm link, we performed a scoping review of published empirical findings on the association between SEP assessed from prenatal development to adulthood and DNAm measured across the life course, with an emphasis on exploring how the developmental timing, duration, and type of SEP exposure influenced DNAm. Results Across the 37 identified studies, we found that: (1) SEP-related DNAm signatures varied across the timing, duration, and type of SEP indicator; (2) however, longitudinal studies examining repeated SEP and DNAm measures are generally lacking; and (3) prior studies are conceptually and methodologically diverse, limiting the interpretability of findings across studies with respect to these three SEP features. Conclusions Given the complex relationship between SEP and DNAm across the lifespan, these findings underscore the importance of analyzing SEP features, including timing, duration, and type. To guide future research, we highlight additional research gaps and propose four recommendations to further unravel the relationship between SEP and DNAm.

Finding genetic factors associated with cognitive abilities

The article provides an overview of the results of modern genetic studies of human cognitive abilities. Finding genetic factors, associated with cognitive abilities, will have far-reaching ramifications at all levels of understanding from DNA to brain and to behavior. Despite its complexity, cognitive ability is a reasonable candidate for molecular genetic research because it is one of the most heritable features of behavior. The first attempts to find genetic factors, associated with cognitive abilities, focused on genes, involved in brain development and function, but this direction proved to be unproductive, as it turned out that there are about 18.000 genes, and it was too difficult to detect among them those genes that are involved in cognitive processes. In addition, a considerable number of genetic factors of human traits are single-nucleotide polymorphisms (SNPs) which are in non-coding DNA regions rather than in traditional genes. The effect of each separate SNP is unimportant, and a clear expression of the general cognitive ability is noticeable only if all the associated SNPs are involved. Currently, over 11,000 such SNPs have been identified, which are uneven in different functional regions of the genome: over 60 % in gene introns, almost 30 % in intergenic DNA regions, about 5 % in gene exons, and about 5 % in transcribed regions (downstream, upstream) and frame regions (UTR'5, UTR'3) of genes. Also there are found 74 SNPs, associated with school achievements. These SNPs are disproportionately located in genes that regulate transcription and alternative splicing of other genes, which are expressed in nerve tissues of the brain during its prenatal development. Finding genetic factors that explain the inheritance of cognitive abilities is important for both science and society. Information about these factors can be used in other fields of human science – human genetics and medicine. It will open up new scientific horizons for education too owing to understanding of the genetic aspects of learning and memory