Effects of gravity, microgravity or microgravity simulation on early mouse embryogenesis: A review of the first two space embryo studies.

Many simulated micro-gravity (micro-G) experiments on earth suggest that micro-G conditions are not compatible with early mammalian embryo development. Recently, the first two "space embryo" studies have been published showing that early mouse embryo development can occur in real microgravity (real micro-G) conditions in orbit. In the first of these studies, published in 2020, Lei and collaborators developed automated mini-incubator (AMI) devices for mouse embryos facilitating cultivation, microscopic observation, and fixation.

Heavy Metals in Umbilical Cord Blood: Effects on Epigenetics and Child Development.

Heavy metals like arsenic, mercury, cadmium, and lead are harmful pollutants that can change how our genes are regulated without altering the DNA sequence, specifically through a process called DNA methylation (DNAm) at 5-methylcytosine, an epigenetic mark that we will focus on in this review. These changes in DNAm are most sensitive during pregnancy, a critical time for development when these modifications can affect how traits are expressed. Historically, most research on these environmental effects has focused on adults, but now there is more emphasis on studying the impacts during early development and childhood.

A Single Cell Transcriptomic Fingerprint of Stressed Premature, Imbalanced Differentiation of Embryonic Stem Cells.

Background: Miscarriages cause a greater loss-of-life than cardiovascular diseases, but knowledge about environmentally induced miscarriages is limited. Cultured naïve pluripotent embryonic stem cells (ESC) differentiate into extra-embryonic endoderm/extraembryonic endoderm (XEN) or formative pluripotent ESC, during the period emulating maximal miscarriage of peri-implantation development. In previous reports using small marker sets, hyperosmotic sorbitol, or retinoic acid (RA) decreased naïve pluripotency and increased XEN by FACS quantitation.

Translational toxicoepigenetic Meta-Analyses identify homologous gene DNA methylation reprogramming following developmental phthalate and lead exposure in mouse and human offspring.

Although toxicology uses animal models to represent real-world human health scenarios, a critical translational gap between laboratory-based studies and epidemiology remains. In this study, we aimed to understand the toxicoepigenetic effects on DNA methylation after developmental exposure to two common toxicants, the phthalate di(2-ethylhexyl) phthalate (DEHP) and the metal lead (Pb), using a translational paradigm that selected candidate genes from a mouse study and assessed them in four human birth cohorts. Data from mouse offspring developmentally exposed to DEHP, Pb, or control were used to identify genes with sex-specific sites with differential DNA methylation at postnatal day 21.

Biological Aging Acceleration Due to Environmental Exposures: An Exciting New Direction in Toxicogenomics Research.

Biological clock technologies are designed to assess the acceleration of biological age (B-age) in diverse cell types, offering a distinctive opportunity in toxicogenomic research to explore the impact of environmental stressors, social challenges, and unhealthy lifestyles on health impairment. These clocks also play a role in identifying factors that can hinder aging and promote a healthy lifestyle. Over the past decade, researchers in epigenetics have developed testing methods that predict the chronological and biological age of organisms.

Novel high throughput screen reports that benzo(a)pyrene overrides mouse trophoblast stem cell multipotency, inducing SAPK activity, HAND1 and differentiated trophoblast giant cells.

Introduction: Cultured mouse trophoblast stem cells (mTSC) maintain proliferation/normal stemness (NS) under FGF4, which when removed, causes normal differentiation (ND). Hypoxic, or hyperosmotic stress forces trophoblast giant cells (TGC) differentiate. Hypoxic, hyperosmotic, and genotoxic benzo(a)pyrene (BaP), which is found in tobacco smoke, force down-regulation of inhibitor of differentiation (Id)2, enabling TGC differentiation.

Pathological epigenetic events and reversibility review: the intersection between hallmarks of aging and developmental origin of health and disease.

We discuss pathological epigenetic events that are reversible (PEERs). A recent study by Poganik and colleagues showed that severe stress in mice and humans transiently elevates biological age of several tissues, and this transient age increase is reversible when the stress is removed. These studies suggest new strategies for reversing normal aging.

Evaluation of pediatric epigenetic clocks across multiple tissues.

Background: Epigenetic clocks are promising tools for assessing biological age. We assessed the accuracy of pediatric epigenetic clocks in gestational and chronological age determination.

Results: Our study used data from seven tissue types on three DNA methylation profiling microarrays and found that the Knight and Bohlin clocks performed similarly for blood cells, while the Lee clock was superior for placental samples.

Epigenetic Reprogramming in and : From Fertilization to Primordial Germ Cell Development.

In this review, advances in the understanding of epigenetic reprogramming from fertilization to the development of primordial germline cells in a mouse and embryo are discussed. To gain insights into the molecular underpinnings of various diseases, it is essential to comprehend the intricate interplay between genetic, epigenetic, and environmental factors during cellular reprogramming and embryonic differentiation. An increasing range of diseases, including cancer and developmental disorders, have been linked to alterations in DNA methylation and histone modifications.

A single cell transcriptomic fingerprint of stressed premature, imbalanced differentiation of embryonic stem cells.

Cultured naïve pluripotent ESC differentiate into first lineage, XEN or second lineage, formative pluripotency. Hyperosmotic stress (sorbitol), like retinoic acid, decreases naive pluripotency and increases XEN in two ESC lines, as reported by bulk and scRNAseq, analyzed by UMAP. Sorbitol overrides pluripotency in two ESC lines as reported by bulk and scRNAseq, analyzed by UMAP.

Analysis of Pregnancy Complications and Epigenetic Gestational Age of Newborns.

Importance: Preeclampsia, gestational hypertension, and gestational diabetes, the most common pregnancy complications, are associated with substantial morbidity and mortality in mothers and children. Little is known about the biological processes that link the occurrence of these pregnancy complications with adverse child outcomes; altered biological aging of the growing fetus up to birth is one molecular pathway of increasing interest.

Objective: To evaluate whether exposure to each of these 3 pregnancy complications (gestational diabetes, gestational hypertension, and preeclampsia) is associated with accelerated or decelerated gestational biological age in children at birth.

Epigenetics: new insights into postoperative adhesion development.

Background: The link between post-operative adhesion development and epigenetic modifications is important in understanding the mechanism behind their formation. The aim of this study was to determine whether epigenetic differences exist between primary fibroblasts of normal peritoneum and adhesion tissues isolated from the same patient(s).

Methods: DNA from fibroblasts isolated from normal peritoneum and adhesion tissues was isolated using Qiagen's EZ1 Advanced Kit.

10 Years of Toxicogenomics section in Frontiers in Genetics: Past discoveries and Future Perspectives.

The Frontiers Media family has over 200 journals, which are each headed by usually one Field Chief Editor, and several thousand specialty sections, which are each headed by one or more Specialty Chief Editors. The year 2021 was the 10th anniversary of the founding of the Frontiers in Genetics journal and the Frontiers in Toxicogenomics specialty section of this journal. In 2021, we also announce one of the newest of the Frontiers journals-Frontiers in Toxicology which is part of the Frontiers Media family of journals but independent of Frontiers in Genetics.

Using high throughput screens to predict miscarriages with placental stem cells and long-term stress effects with embryonic stem cells.

A problem in developmental toxicology is the massive loss of life from fertilization through gastrulation, and the surprising lack of knowledge of causes of miscarriage. Half to two-thirds of embryos are lost, and environmental and genetic causes are nearly equal. Simply put, it can be inferred that this is a difficult period for normal embryos, but that environmental stresses may cause homeostatic responses that move from adaptive to maladaptive with increasing exposures.

IL-10: A possible immunobiological component of positive mental health in refugees.

Objective: As the number of refugees continues to rise, there is growing concern about the impact from trauma exposures on their mental health. However, there is a limited understanding of possible biological mechanisms contributing to the substantial inter-individual differences in trauma-related outcomes, especially as it relates to positive mental health. Only sparse work has focused on the biology of positive mental health, including energy and sleep, in trauma-exposed persons.

Using Live Imaging and Fluorescence Ubiquitinated Cell Cycle Indicator Embryonic Stem Cells to Distinguish G1 Cell Cycle Delays for General Stressors like Perfluoro-Octanoic Acid and Hyperosmotic Sorbitol or G2 Cell Cycle Delay for Mutagenic Stressors like Benzo(a)pyrene.

Lowest observable adverse effects level (LOAEL) is a standard point-of-departure dose in toxicology. However, first observable adverse effects level (FOAEL) was recently reported and is used, in this study, as one criterion to detect a mutagenic stimulus in a live imager. Fluorescence ubiquitinated cell cycle indicator (FUCCI) embryonic stem cells (ESC) are green in the S-G2-M phase of the cell cycle and not green in G1-phase.

Prenatal Exposures to Common Phthalates and Prevalent Phthalate Alternatives and Infant DNA Methylation at Birth.

Phthalates are a diverse group of chemicals used in consumer products. Because they are so widespread, exposure to these compounds is nearly unavoidable. Recently, growing scientific consensus has suggested that phthalates produce health effects in developing infants and children.

Using Live Imaging and FUCCI Embryonic Stem Cells to Rank DevTox Risks: Adverse Growth Effects of PFOA Compared With DEP Are 26 Times Faster, 1,000 Times More Sensitive, and 13 Times Greater in Magnitude.

Fluorescent ubiquitination-based cell cycle indicator (FUCCI) embryonic stem cells (ESCs), which fluoresce green during the S-G2-M phases, generate an S-shaped curve for the accumulation of cells during normal stemness (NS) culture with leukemia-inhibitory factor (LIF). Since it was hypothesized that a culture of ESCs was heterogeneous in the cell cycle, it was expected that increased S-G2-M-phases of the cell cycle would make an S-shaped curve parallel to the accumulation curve. Unexpectedly, it was observed that the fraction of FUCCI ESCs in green decreases over time to a nadir at ∼24 h after previous feeding and then rapidly enters S-G2-M-phases after medium change.