Epigenetic clocks reveal a rejuvenation event during embryogenesis followed by aging

The notion that the germ line does not age goes back to the 19th-century ideas of August Weismann. However, being metabolically active, the germ line accumulates damage and other changes over time, i.e., it ages. For new life to begin in the same young state, the germ line must be rejuvenated in the offspring. Here, we developed a multi-tissue epigenetic clock and applied it, together with other aging clocks, to track changes in biological age during mouse and human prenatal development. This analysis revealed a significant decrease in biological age, i.e., rejuvenation, during early stages of embryogenesis, followed by an increase in later stages. We further found that pluripotent stem cells do not age even after extensive passaging and that the examined epigenetic age dynamics is conserved across species. Overall, this study uncovers a natural rejuvenation event during embryogenesis and suggests that the minimal biological age (ground zero) marks the beginning of organismal aging.

Epigenetic clocks reveal a rejuvenation event during embryogenesis followed by aging

The notion that germline cells do not age goes back to the 19th century ideas of August Weismann. However, being in a metabolically active state, they accumulate damage and other age-related changes over time, i.e., they age. For new life to begin in the same young state, they must be rejuvenated in the offspring. Here, we developed a new multi-tissue epigenetic clock and applied it, together with other aging clocks, to track changes in biological age during mouse and human prenatal development. This analysis revealed a significant decrease in biological age, i.e. rejuvenation, during early stages of embryogenesis, followed by an increase in later stages. We further found that pluripotent stem cells do not age even after extensive passaging and that the examined epigenetic age dynamics is conserved across species. Overall, this study uncovers a natural rejuvenation event during embryogenesis and suggests that the minimal biological age (the ground zero) marks the beginning of organismal aging.

MORPHOLOGICAL FEATURES OF FASCIAL STRUCTURES IN INFRAHYOID NECK DURING PRENATAL HUMAN ONTOGENESIS

Fascia and fascial spaces of the neck remains a controversial morphological question, which requires in-depth study, especially in the focus of prenatal morphogenesis. We have examined specimens of human embryos, prefetuses and fetuses in order to study the development and topographic-anatomical features of the neck fascial structures at different stages of human prenatal development. For this purpose, a set of microscopic methods (three-dimensional reconstruction, series of histological sections examination) for embryos (8.0-13.0 mm PCL (parieto-coccygeal length) and prefetuses (14.0-80.0 mm PCL) was used; macroscopic examination for fetuses’ specimens (80.0-230.0 mm PCL). It was found that at the end of the embryonic period of development, there are rudiments of the larynx and pharynx, which are not delimited; precrusors of vascular and nerve trunks of the neck are already present. In the prefetal we may observe change from the bilaminar to multilaminar fascial morphology. The definitive structure of fascial structures may be found in fetal stage of human ontogenesis. It is important that at fetal stage, fascial leaves tend to fuse in areas that contact with the periosteum or in the fascial spaces that do not yet contain adipose tissue yet.

Sex Determination Using RNA-Sequencing Analyses in Early Prenatal Pig Development

Sexual dimorphism is a relevant factor in animal science, since it can affect the gene expression of economically important traits. Eventually, the interest in the prenatal phase in a transcriptome study may not comprise the period of development in which male and female conceptuses are phenotypically divergent. Therefore, it would be interesting if sex differentiation could be performed using transcriptome data, with no need for extra techniques. In this study, the sex of pig conceptuses (embryos at 25 days-old and fetuses at 35 days-old) was determined by reads counts per million (CPM) of Y chromosome-linked genes that were discrepant among samples. Thus, ten genes were used: DDX3Y, KDM5D, ZFY, EIF2S3Y, EIF1AY, LOC110255320, LOC110257894, LOC396706, LOC100625207, and LOC110255257. Conceptuses that presented reads CPM sum for these genes (ΣCPMchrY) greater than 400 were classified as males and those with ΣCPMchrY below 2 were classified as females. It was demonstrated that the sex identification can be performed at early stages of pig development from RNA-sequencing analysis of genes mapped on Y chromosome. Additionally, these results reinforce that sex determination is a mechanism conserved across mammals, highlighting the importance of using pigs as an animal model to study sex determination during human prenatal development.

EMBRYOGENESIS OF THE HUMAN RESPIRATORY SYSTEM

One of the topical issues of morphology is studying general regulations of development and structural formation dynamics of respiratory system. The aim of the study was to determine peculiarities of the embryogenesis of respiratory system organs during prenatal development in humans. Research was conducted on 22 series of histological specimens of human embryos which were 4,5-8,0 mm of parieto-cocygeal lengths (PLC), and by using complex morphological methods of study (morphometry, histological assessment, three-dimensional reconstruction). It was established that the source of human lungs primordium is a traheopulmonary primordium, which at the end of 4th week of human prenatal development is represented by an odd bud-shaped entity which departs with an acute angle from the ventral wall of the foregut and is located in front of foregut. The beginning of the 5th week of human prenatal development is considered to be a critical period, which holds intensive processes of organogenesis of the respiratory system and is a possible time for the occurrence of some congenital defects or anomalies and structural variants. Sources of pulmonary vessels are islands of intraorgan hematopoiesis and extraorgan main vessels, communication between which occurs during the end of 4th and at the start of 5th weeks of human prenatal development.

Soluble Epoxide Hydrolase as a Potential Key Factor for Human Prenatal Development

Soluble epoxide hydrolase (sEH) converts highly active epoxyeicosatrienoic acids (EETs) generated by cytochrome P450 (CYP) epoxygenases from arachidonic acid to less active dihydroxyeicosatrienoic acids. Because of the role of EETs in processes potentially relevant to the development of organisms, EETs could be suggested as potential morphogens. Unfortunately, only little is known about sEH expression during human intrauterine development (IUD). We investigated the spatio-temporal expression pattern of sEH in human embryonic/foetal intestines, liver and kidney from the 6th to the 20th week of IUD by two-step immunohistochemistry. sEH was expressed during the whole tested period of prenatal development and its level of expression remained more or less the same during the estimated period of IUD. Distribution of CYP epoxygenases and sEH in the intestinal epithelium and the nephrogenic zone of the kidney suggests an influence of EETs on cell proliferation and differentiation and, consequently, on the development of intestines and kidney. Thus, alterations in the strict spatio-temporal pattern of expression of CYP epoxygenases and/or sEH during human prenatal development by xenobiotics could have a harmful impact for developing organisms.