Epigenetic modification takes place in many types of environment. Undesirable epigenetic changes for the postnatal life at the developmental stage are induced in utero by exposure to harsh environment such as endocrine disruptors, severe psychological stress and insufficient or excessive nutrition. Some of these changes continues even for a long time after birth from womb to tomb. Under these circumstances with an unhealthy life style, such as higher caloric intake, insufficient exercise, or stress, there is a higher risk of developing various illnesses including lifestyle-related diseases, such as essential hypertension, type 2 diabetes mellitus, dyslipidemia, psychological disorders and cancers. An illness goes through these two steps, first having origins in the early stage of life and secondary exposure of unhealthy life. In addition, some of these modifications have a tendency to be transmitted to the next generations, (transgenerational effect). This is the concept of Developmental Origins of Health and Disease theory (DOHaD). The incidence of noncommunicable diseases (NCDs) have been markedly increasing, especially in developing countries, and the prevention of these diseases is a high-profile objective for world economic growth. In addition to birth weight, specific epigenetic modifications are expected to be good marks for developing illness in later life. With analysis of these makers, even for the individuals with a higher risk, the illness development will be expected to be effectively controlled through intervention in the early stage. Research on predicting markers, and intervention supplements, and pharmacological materials for higher risk individuals has been progressing considerably. This DOHaD theory is expected to be highly beneficial for the prevention of many illnesses.
Epidemiological studies suggest that exposure to prenatal stressors, including malnutrition, maternal immune activation (MIA), and adverse life events, is associated with increased risks of schizophrenia, autism spectrum disorder (ASD), and attention-deficit hyperactivity disorder (ADHD). However, the underlying pathophysiological mechanisms are unclear. The first trimester of pregnancy is particularly a vulnerable period. During this period, the self-renewal of neural stem cells and neurogenesis vigorously occur, and synaptic connections are partially formed in the telencephalon. Disturbance of this neuronal proliferation and migration during the first trimester may underlie the increased susceptibility to these disorders. Epigenetic modifications, such as DNA methylation and histone modification, are critical mechanisms for regulating gene expression. They can be affected by stress and are associated with an increase in susceptibility to schizophrenia and developmental disabilities. Injection of polyinosinic–polycytidylic acid or lipopolysaccharide induces MIA, enhances the expression of proinflammatory cytokines, and leads to the activation of microglia and the subsequent epigenetic modification of neurons or glia in the offspring. Furthermore, maternal high-fat diet and obesity similarly induce MIA and therefore may increase the risk of developmental disabilities. In addition, maternal stress reprograms the hypothalamic–pituitary–adrenal (HPA) axis, which regulates the stress response in the offspring. Thus, exposure to prenatal stress may increase the susceptibility to schizophrenia, ASD, or ADHD in the offspring through epigenetic modifications, MIA, and alteration of the HPA axis.
Foetal environmental factors, including maternal nutrition, hormonal disturbance, and chemical exposure, affect foetal growth and can cause birth defects. Recent studies have shown the link of poor foetal growth with increased risks of coronary heart disease, type II diabetes, kidney disease, and brain disorders in adulthood. Epigenetic modifications, such as DNA methylation and histone modifications, are involved in tissue- and developmental stage-specific gene expression and silencing, and they can be transmitted stably through mitotic cell division, thereby inducing long-term changes in gene regulation. Developmental programming during the foetal period, therefore, could affect adult health through epigenetic mechanisms. In fact, many studies using animal models have demonstrated that nutrient manipulation during pregnancy induces epigenetic alterations at specific loci or globally in the offspring. In this review, we summarize our findings that elucidate the effects of in utero environments on the human placental epigenome.
Epigenetics is an important mechanism of gene regulation that is dependent on the chromatin structure, which is determined by the epigenetic chemical modification of DNA and histone proteins. It is known that the failure of epigenetic mechanisms causes congenital neurodevelopmental disorders (NDs), and that early life exposure to mental stress and endocrine disrupting chemicals, such as phthalates, bisphenol A, and tobacco, can change epigenetic mechanism and gene expression in the brain and cause NDs. Moreover, environmentally induced epigenetic changes are not erased during gametogenesis and are transmitted to subsequent generations, leading to changes in behavior phenotypes. However, epigenetics has a reversible nature because it is based on the addition or removal of chemical residues, and thus the original epigenetic status may be restored. Indeed, several drugs used for mental disorders and NDs restore the epigenetic state and gene expression. Improved epigenetic understanding of NDs will provide important clues for the development of new drugs that take advantage of epigenetic reversibility.
Objectives: To clarify the predisposing factors associated with blood loss after delivery in mothers with full-term singleton babies.
Methods: In this retrospective cohort study, we investigated 1,294 women who delivered singleton babies vaginally in 2011 at a medical center in Tokyo. We determined the amount of blood loss after delivery and covariates of age, parity, pre pregnancy body mass index (BMI), gestational weight gain (GWG), gestational week, pregnancy complications, lifestyles of smoking and drinking, placental weight, and infant weight and sex.
Results: The majority of participants had lost less than 500 ml of blood (n=868, 67%), 21% lost between 500–799 ml of blood (n=273), 12% lost 800 ml or more of blood (n=153). The amount of blood loss statistically increased (p<0.001) as pre pregnancy BMI category level increased from underweight (<18.5 kg/m2), normal (18.5–22.9 kg/m2), to overweight/obesity (≥23 kg/m2). Compared with the least category of GWG <8.2 kg, ≥8.2 kg GWG was statistically associated with a larger amount of blood loss category (p=0.032). Multinomial logistic regression analyses demonstrated that with the reference pre pregnancy BMI 18.5–22.9 kg/m2, obese and obesity mothers with pre pregnancy BMI ≥23 kg/m2 were at an increased risk of blood loss [OR 2.28, 95%confidence interval (95%CI): 1.48–3.50 for the category of 500–799 ml and OR 2.15, 95%CI: 1.29–3.59 for a category of 800 ml≤)]. In addition, pregnancy induced hypertension (PIH) (p=0.010) and infant weight (p<0.0001) significantly increased the risk of blood loss.
Conclusions: In mothers with full-term singleton babies, increased pre pregnancy BMI overweight/obesity, PIH, and infant weight, were suggested to be risk factors for increased amount of blood loss.
Objectives: In this study, we investigated the association between subjective school adaptation and life skills in elementary school children with chronic diseases.
Methods: A cross-sectional sample of children with chronic diseases (n=76), who were being treated as pediatric outpatients and who were in the 4th to 6th grade of public elementary schools, was selected. The subjects completed a self-administered questionnaire that comprised an Adaptation Scale for School Environments on Six Spheres (ASSESS) and life skills scales for self-management and stress coping strategies. Structural equation modeling was conducted to identify the inter-relationship between subjective school adaptation and life skills.
Results: Compared with the gender- and schoolyear-matched healthy controls (n=380), a large number of children with chronic diseases had low scores on the measure of interpersonal relationship in school. From the structural equation modeling, the subscales “friend’s support” and “victimized relationship” in interpersonal relationship were two of the factors closely related to subjective adaptation of learning as well as school satisfaction in the children with chronic diseases. Furthermore, the “decision-making” and “goal-setting” components of self-management skills demonstrated positive contributions to the adaptation of learning and interpersonal relationship either directly affected by the skills themselves or through the affirmative effects of stress coping strategies.
Conclusions: These results suggest that life skills education, focusing on self-management and stress coping strategies along with support to improve interpersonal relationships, is effective in promoting subjective school adaptation and leads to increased school satisfaction in children with chronic diseases.
Recently, a tropical freshwater fish, the zebrafish, has been generally used as a useful model organism in various fields of life science worldwide. The zebrafish model has also been applied to environmental toxicology; however, in Japan, it has not yet become widely used. In this review, we will introduce the biological and historical backgrounds of zebrafish as an animal model and their breeding. We then present the current status of toxicological experiments using zebrafish that were treated with some important environmental contaminants, including cadmium, organic mercury, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and tributyltin. Finally, the future possible application of genetically modified zebrafish to the study of environmental toxicology is discussed.
More than sixty years has passed since the outbreak of Minamata disease, and high-level methylmercury contaminations now seem nonexistent in Japan. However, mercury has been continuously discharged from natural sources and industrial activities, and the health effects on children susceptible to methylmercury exposure at low levels, in addition to mercury contamination from mercury or gold mining areas in developing countries, become a worldwide concern. In this article, we provide a recent overview of epidemiological studies regarding methylmercury and mercury. The following findings were obtained. (1) Many papers on exposure assessment of methylmercury/mercury have been published since the Minamata Convention on Mercury was adopted in 2013. (2) The most crucial problem is child developmental neurotoxicity resulting from prenatal exposure to methylmercury, but its precise assessment seems to be difficult because most of such effects are neither severe nor specific. (3) Several problems raised in birth cohort studies (e.g., whether IQ deficits due to prenatal methylmercury exposure remain when the children become adults, or whether the postnatal exposure at low levels also causes such adverse effects in children) remain unsolved. (4) Concurrent exposure models of methylmercury, lead, polychlorinated biphenyls, aresenic, and organochlorine pesticides, as well as possible antagonists such as polyunsaturated fatty acids and selenium, should be considered in the study design because the exposure levels of methylmercury are extremely low in developed countries. (5) Further animal experiments and molecular biological studies, in addition to human studies, are required to clarify the mechanism of methylmercury toxicity.
We reported the evaluations of the carcinogenicity of fluoro-edinite, silicon carbide, and carbon nanotubes performed by IARC working group in October 2014. For carbon nanotubes (CNTs), multi-walled carbon nanotube (MWCNT)-7 was classified as Group 2B, and MWCNTs without MWCNT-7 and single-walled carbon nanotubes (SWCNTs) were classified as not classifiable in terms of their carcinogenicity to humans. There is sufficient evidence of carcinogenicity for MWCNT-7 in experimental animals, limited evidence for other MWCNTs, and inadequate evidence for SWCNTs. The mechanic evidence for CNTs was not strong. Fluoro-edinite was classified as carcinogenic to humans (Group 1) on the basis of sufficient evidence of carcinogenicity to humans and experimental animals. Silicon carbide was classified into silicon carbide fibers and whiskers. Silicon carbide fibers were evaluated as possibly carcinogenic to humans (Group 2B) on the basis of limited evidence of carcinogenicity to humans. Silicon carbide whiskers were evaluated as probably carcinogenic to humans (Group 2A) on the basis of sufficient evidence of carcinogenicity to experimental animals and the similarity of their physicochemical properties to those of asbestos in terms of the mechanism of carcinogenicity. We report the process of progression in meeting and discuss how to determine the evidence and the evaluation of the carcinogenicity of the three materials.
Objectives: As part of the Kumamoto RAINBOW Project, a multifaceted implementation of the prevention of premature labor, we investigated pregnant women’s oral health status and assessed the validity of a self-reported periodontal disease questionnaire.
Methods: We examined the oral health status of pregnant women and asked them for subjective descriptions of symptoms of periodontitis both in the first and the second half of their pregnancy in Kumamoto Prefecture from August 2012 to January 2014. The Community Periodontal Index (CPI) was used to assess the periodontal condition, and women having periodontal pockets with depths of ≥4 mm were catecogorized as having periodontitis. The results were the scores of the self-questionnaire for periodontal disease prepared by the Japan Dental Association.
Results: Of the 9,527 pregnant women who received periodontal check- ups during the first half of pregnancy, 32 percent were diagnosed as having periodontitis. The self-questionnaire had a sensitivity of 51.2% and a specificity of 62.9% for pregnant women to predict their periodontal disease. Then, we evaluated the importance of each question by logistic regression analysis and extracted the useful items. An increased sensitivity (79.9%) was obtained with the best of the modified questionnaire.
Conclusions: To our knowledge, this is the first report of the evaluation of the usefulness of the self-reported periodontal disease questionnaire for pregnant women. The current self-questonnaire used for the general adult population was less sensitive for pregnant women. Our modified questionnaire showed an improved sensitivity for diagnosing periodontitis, but its specificity remained low. A specialized self-questionnaire for periodontal disease in pregnant women should be designed.