Dynamic Proteome Landscape During Preimplantation Human Embryo Development and Trophectoderm Stem Cell-Differentiation.

Embryo development involves fertilization of a mature ovum, which, after sequential cell divisions (2-,4-8-cells and morula), undergoes differentiation into implantation competent blastocyst. The blastocyst comprises of inner cell mass surrounded by an outer layer of cells called the trophoblast (TSblast) that, upon attachment to the endometrium, differentiates into extravillous trophoblasts (EVTs) that facilitates embryo invasion into the endometrium for intrauterine embryo development, and syncytiotrophoblast (ST) that form the placenta. Such cellular differentiation stages are critical for embryogenesis and implantation, although the protein expression landscape remains poorly understood in humans.

Leveraging chorionic villus biopsies for the derivation of patient-specific trophoblast stem cells.

Human trophoblast stem (TS) cells are informative in vitro models for the generation and testing of biologically meaningful hypotheses. The goal of this project was to derive patient-specific TS cell lines from clinically available chorionic villus biopsies. Cell outgrowths were captured from human chorionic villus tissue specimens cultured in modified human TS cell medium.

Syncytin-1 Is Responsible for the Fusion Between Human Trophoblasts and Endometrial Stromal Cells.

Syncytiotrophoblasts (STs) are multinucleated cells formed by the fusion of trophoblasts and play critical roles in placental development and function. Retrovirus-derived fusogenic proteins, known as syncytins, regulate trophoblast fusion by interacting with specific receptors. In humans, two syncytins, Syncytin-1 (Syn1) and Syncytin-2 (Syn2), have been identified.

Association of birth outcomes with maternal and infant FADS1 rs174547 genotypes in Japanese participants.

N-3 long-chain polyunsaturated fatty acids (n-3LCPUFAs) are crucial for child growth and development particularly for fetal growth in utero and brain development and function. This study examined the relationship between birth outcomes and FADS1 rs174547 genotypes in Japanese mothers and infants. The study included 406 mothers and 373 infants, i.

Effects of an aryl hydrocarbon receptor ligand on human trophoblast cell development.

Study Question: How does activation of aryl hydrocarbon receptor (AHR) signaling affect human trophoblast cell development and differentiation?

Summary Answer: AHR activation alters gene expression without impairing the ability of trophoblast cells to maintain a stem cell state or differentiate into essential cell types, such as extravillous trophoblast (EVT) cells or syncytiotrophoblast (ST), while promoting the production of 2-methoxy estradiol (2ME), which may impact placental development.

What Is Known Already: The placenta serves both as a nutrient delivery system and a protective barrier against environmental toxins. AHR signaling is known to mediate cellular responses to environmental pollutants, potentially affecting trophoblast cell function, but the specific impacts of AHR activation on these cells were not fully understood.

Plates made from magnesium alloy with a long period stacking ordered structure promote bone formation in a rabbit fracture model.

Operative treatment is an option for fractures when the fracture is unstable or the patient wishes to return early to daily life or social activities. Metal plates such as titanium and stainless steel are often used in fracture surgery, but the metal plate lacks bone-healing activity and is not bioabsorbable, requiring a second surgery to remove it after bone union. Here we show that a magnesium (Mg) plate made from an alloy of yttrium, zinc, and aluminum with magnesium as the main component in a long-period stacking ordered structure promotes bone formation in a rabbit tibia fracture model and is also bioabsorbable.

Association between paternal physique and obesity in children at the age of 3 years: the Japan Environment and Children's Study.

Obesity during development has been reported to be a determinant factor in the future development of non-communicable diseases (NCDs). Parental obesity is suggested to be a predictor of children's obesity, and it is important to consider parental factors to prevent NCDs in the progeny. Previously, we showed that paternal height had a stronger association with infant birth weight than paternal body mass index (BMI) in the Japanese population.

Prospective association of daily toothbrushing frequency and the prevalence of childhood functional constipation: the Japan Environment and Children's Study.

Functional constipation is the most common gastrointestinal disorder during childhood. Oral stimulation (mastication and toothbrushing) reportedly improves bowel movements, but the association between daily toothbrushing behavior and functional constipation remains unknown. Data (n = 83,660) from fetal records (n = 104,059) in the Japan Environment and Children's Study, an ongoing prospective birth cohort, were analyzed to investigate the impact of daily toothbrushing frequency on functional constipation during childhood, using ROME III diagnostic criteria.

Impact of maternal smoking and secondhand smoke exposure during singleton pregnancy on placental abruption: analysis of a prospective cohort study (the Japan Environment and Children's Study).

Objectives: This study aimed to investigate the association and population-attributable fraction (PAF) of maternal smoking and secondhand smoke (SHS) exposure during pregnancy with placental abruption.

Design: Prospective cohort study.

Setting: 15 regional centres in Japan.

Non-canonical imprinting, manifesting as post-fertilization placenta-specific parent-of-origin dependent methylation, is not conserved in humans.

Genomic imprinting is the parent-of-origin dependent monoallelic expression of genes often associated with regions of germline-derived DNA methylation that are maintained as differentially methylated regions (gDMRs) in somatic tissues. This form of epigenetic regulation is highly conserved in mammals and is thought to have co-evolved with placentation. Tissue-specific gDMRs have been identified in human placenta, suggesting that species-specific imprinting dependent on unorthodox epigenetic establishment or maintenance may be more widespread than previously anticipated.

Advanced maternal age is a risk factor for both early and late gestational diabetes mellitus: The Japan Environment and Children's Study.

Aims: This study investigated the association between maternal age and early and late gestational diabetes mellitus (GDM).

Methods: In total, 72,270 pregnant women were included in this prospective birth cohort study. Associations between maternal age and early GDM (diagnosed at <24 gestational weeks) and late GDM (diagnosed at ≥24 gestational weeks) were evaluated using a multinomial logistic regression model with possible confounding factors.

Bruxism associated with short sleep duration in children with autism spectrum disorder: The Japan Environment and Children's Study.

Bruxism, the involuntary activity of masticatory muscles, is common among individuals with autism spectrum disorders (ASD). Although bruxism is bidirectionally associated with sleep issues, whether an infant's sleep duration contributes to the development of bruxism remains unknown. In this study, a dataset (n = 83,720) obtained from the Japan Environment and Children's Study, a nationwide birth cohort study, was subjected to multiple imputations using logistic regression analysis with adjustments for several maternal and child-related variables.

Epigenetic dynamics of partially methylated domains in human placenta and trophoblast stem cells.

Background: The placenta is essential for nutrient exchange and hormone production between the mother and the developing fetus and serves as an invaluable model for epigenetic research. Most epigenetic studies of the human placenta have used whole placentas from term pregnancies and have identified the presence of partially methylated domains (PMDs). However, the origin of these domains, which are typically absent in most somatic cells, remains unclear in the placental context.

NOTUM-mediated WNT silencing drives extravillous trophoblast cell lineage development.

Trophoblast stem (TS) cells have the unique capacity to differentiate into specialized cell types, including extravillous trophoblast (EVT) cells. EVT cells invade into and transform the uterus where they act to remodel the vasculature facilitating the redirection of maternal nutrients to the developing fetus. Disruptions in EVT cell development and function are at the core of pregnancy-related disease.

Aryl Hydrocarbon Receptor Activation Drives 2-Methoxy Estradiol Secretion in Human Trophoblast Stem Cell Development.

Study Question: How does activation of AHR signaling affect human trophoblast cell development and differentiation?

Summary Answer: AHR activation leads to altered gene expression but does not hinder the ability of trophoblast cells to remain in a stem cell state or differentiate into essential cell types, such as extravillous trophoblast cells (EVT) or syncytiotrophoblast (ST). It also promotes the production of 2 methoxy estradiol (2ME), a compound that could influence placental development.

What Is Known Already: The placenta serves both as a nutrient delivery system and a protective barrier against environmental toxins.

Association of maternal blood and umbilical cord blood plasma fatty acid levels with the body size at birth of Japanese infants.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), mainly obtained from fish, have been implicated in fetal development. Because few studies have examined maternal and umbilical cord blood fatty acid levels and infant body size in Japan with a fish-eating culture, we examined differences in plasma fatty acid levels in pregnant women and infant size at birth. This study is a large birth cohort study of 1476 pairs of Japanese pregnant women and their infants.

Leveraging chorionic villus biopsies for the derivation of patient-specific trophoblast stem cells.

Human trophoblast stem () cells are an informative in vitro model for the generation and testing of biologically meaningful hypotheses. The goal of this project was to derive patient-specific TS cell lines from clinically available chorionic villus sampling biopsies. Cell outgrowths were captured from human chorionic villus tissue specimens cultured in modified human TS cell medium.

Association Between Maternal Physical Activity From Pre-pregnancy to Child-rearing and Their Children's Physical Activity in Early Childhood Among Japanese.

Introduction: This study aimed to determine the association between cumulative maternal physical activity level and their children's physical activity in early childhood. We also compared the influence of each maternal physical activity on children's physical activity in early childhood.

Methods: We analyzed the data from 1,067 Japanese mother-child pairs.

Maternal birth weight is an indicator of preterm delivery: the Japan environment and children's study.

This study aimed to investigate the association between maternal birth weight (MBW) with preterm delivery (PTD) in the Japanese population. To this end, a total of 78,972 Japanese pregnant women were included in a prospective birth cohort study. Multiple logistic regression and multinominal logistic regression models were applied to investigate the associations of MBW with PTD (delivery from 22 to < 37 weeks of gestation), early PTD (delivery from 22 to < 34 weeks), and late PTD (delivery from 34 to < 37 weeks).

NOTUM-MEDIATED WNT SILENCING DRIVES EXTRAVILLOUS TROPHOBLAST CELL LINEAGE DEVELOPMENT.

Trophoblast stem () cells have the unique capacity to differentiate into specialized cell types, including extravillous trophoblast () cells. EVT cells invade into and transform the uterus where they act to remodel the vasculature facilitating the redirection of maternal nutrients to the developing fetus. Disruptions in EVT cell development and function are at the core of pregnancy-related disease.

Association between Maternal Birth Weight and Prevalence of Congenital Malformations in Offspring: The Japanese Environment and Children's Study.

Congenital malformations are functional and structural alterations in embryonic or foetal development resulting from a variety of factors including maternal health status. This study aimed to investigate the association between maternal birth weight (MBW) and the prevalence of congenital malformations in offspring using data from a nationwide birth cohort study in Japan including 103,060 pregnancies. A binary logistic regression model with adjustment for various covariates revealed that an MBW of <2500 g (low MBW) was associated with an increased risk of congenital heart disease (adjusted odds ratio: 1.

Modeling embryo-endometrial interface recapitulating human embryo implantation.

The initiation of human pregnancy is marked by the implantation of an embryo into the uterine environment; however, the underlying mechanisms remain largely elusive. To address this knowledge gap, we developed hormone-responsive endometrial organoids (EMO), termed apical-out (AO)-EMO, which emulate the in vivo architecture of endometrial tissue. The AO-EMO comprise an exposed apical epithelium surface, dense stromal cells, and a self-formed endothelial network.

Maternal birth weight as an indicator of early and late gestational diabetes mellitus: The Japan Environment and Children's Study.

Aims: This study aimed to investigate the association of maternal birth weight (MBW) with early and late gestational diabetes mellitus (GDM).

Methods: A total of 69318 pregnant Japanese women were included in this birth cohort study. The associations between maternal birth weight and early gestational diabetes mellitus (diagnosed at <24 gestational weeks) and late GDM (diagnosed at ≥24 gestational weeks) were investigated using a multinomial logistic regression model, with an maternal birth weight of 3000-3499 g as the reference category.