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Infertility treatment is a possible factor in hypertensive disorders of pregnancy (HDP). Identifying the characteristics of pregnant women who have undergone infertility treatment and have a potential risk for HDP is valuable for its prevention and treatment. Using data from 12,456 pregnant Japanese women from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, the association between infertility treatment and HDP was analyzed. A multiple logistic regression model showed an association between infertility treatment and HDP (odds ratio, 1.34; 95% confidence interval, 1.05–1.72). In vitro fertilization/intracytoplasmic sperm injection were also associated with HDP. Moreover, these associations were observed even among women who were not overweight and did not smoke. The application of infertility treatment should be carefully considered, even among women with low modifiable risk factors.

Although there is substantial information about the effects of social relationships on mental health, their effects on postnatal bonding remain unclear. We aimed to examine the association between social isolation and postnatal bonding disorder. We analyzed data from 17,999 women who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. An abbreviated version of the Lubben Social Network Scale was used to assess social isolation in the second trimester of pregnancy, and its subscales were used to assess marginal family ties and marginal friendship ties. Bonding disorder was defined as a Mother-to-Infant Bonding Scale score of ≥ 5 1 month after delivery. Multiple logistic regression analyses were conducted to examine the association between social isolation and postnatal bonding disorder after adjusting for age at delivery, parity, feelings towards pregnancy, psychological distress during pregnancy, and household income. Analyses stratified by postnatal depressive symptoms (PDS) were also conducted. Social isolation was associated with postnatal bonding disorder: the odds ratio (OR) was 1.55 (95% confidence interval [CI], 1.41-1.71). Marginal family ties and friendship ties were associated with postnatal bonding disorder: the ORs were 1.40 (95% CI, 1.23-1.60) and 1.44 (95% CI, 1.32-1.57), respectively. Marginal family ties were associated with postnatal bonding disorder only among women without PDS: the ORs were 1.30 (95% CI, 1.10-1.55) among women without PDS and 1.13 (95% CI, 0.91-1.40) among women with PDS. Social isolation during pregnancy was associated with an increased risk of postnatal bonding disorder.

Hypertensive disorders of pregnancy increase the risk of adverse maternal and fetal outcomes. In 2018, the Japanese classification of hypertensive disorders of pregnancy was standardized with those of other countries, and a hypertensive disorder of pregnancy was considered to be present if hypertension existed during pregnancy and up to 12 weeks after delivery. Strategies for the prevention of hypertensive disorders of pregnancy have become much clearer, but further research is needed on appropriate subjects and methods of administration, and these have not been clarified in Japan. Although guidelines for the use of antihypertensive drugs are also being studied and standardized with those of other countries, the use of calcium antagonists before 20 weeks of gestation is still contraindicated in Japan because of the safety concerns that were raised regarding possible fetal anomalies associated with their use at the time of their market launch. Chronic hypertension is now included in the definition of hypertensive disorders of pregnancy, and blood pressure measurement is a fundamental component of the diagnosis of hypertensive disorders of pregnancy. Out-of-office blood pressure measurements, including ambulatory and home blood pressure measurements, are important for pregnant and nonpregnant women. Although conditions such as white-coat hypertension and masked hypertension have been reported, determining their occurrence in pregnancy is complicated by the gestational week. This narrative review focused on recent reports on hypertensive disorders of pregnancy, including those related to blood pressure measurement and classification.

Background Low birth weight is associated with an increased risk of developing chronic diseases in adulthood, with a particularly high incidence in Japan among developed countries. Maternal undernutrition is a risk factor for low birth weight, but the association between the timing of food intake and infant birth weight has not been investigated. This study aimed to examine the association between breakfast intake frequency among Japanese pregnant women and infant birth weight. Methods Of all pregnant women who participated in the Tohoku Medical Megabank Project Three Generation Cohort Study, 16,820 who answered the required questions were included in the analysis. The frequency of breakfast intake from pre- to early pregnancy and from early to mid-pregnancy was classified into four groups: every day and 5–6, 3–4, and 0–2 times/week. Multivariate linear regression models were constructed to examine the association between breakfast intake frequency among pregnant women and infant birth weight. Results The percentage of pregnant women who consumed breakfast daily was 74% in the pre- to early pregnancy period and 79% in the early to mid-pregnancy period. The average infant birth weight was 3,071 g. Compared to women who had breakfast daily from pre- to early pregnancy, those who had breakfast 0–2 times/week had lower infant birth weight (β = -38.2, 95% confidence interval [CI]: -56.5, -20.0). Similarly, compared to women who had breakfast daily from early to mid-pregnancy, those who had breakfast 0–2 times/week had lower infant birth weight (β = -41.5, 95% CI: -63.3, -19.6). Conclusions Less frequent breakfast intake before and mid-pregnancy was associated with lower infant birth weight.

Background Hypertensive disorders of pregnancy (HDP) adversely affect the prognosis of mother and child, and the prognosis depends on the subtype of HDP. Skipping breakfast may be associated with increased blood pressure due to disruption of the circadian clock, but the association with the development of HDP has not been studied. The purpose of this study was to examine the association between skipping breakfast and the development of HDP and HDP subtypes in Japanese pregnant women. Methods Of the pregnant women who participated in the Tohoku Medical Megabank Project Three-Generation Cohort Study, 18,839 who answered the required questions were included in the analysis. This study had a cross-sectional design. The breakfast intake frequency from pre-pregnancy to early pregnancy was classified into four groups: daily, 5–6 times per week, 3–4 times per week, and 0–2 times per week. HDP was classified into gestational hypertension (GH), chronic hypertension (CH), preeclampsia (PE), and severe preeclampsia (SuPE). Multiple logistic regression analysis and multinomial logistic analysis were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for breakfast intake frequency and development of HDP or HDP subtypes. We performed a stratified analysis based on energy intake. Results Of the participants, 74.3% consumed breakfast daily, and 11.1% developed HDP. Women who consumed breakfast 0–2 times per week had a higher risk of HDP (OR: 1.33, 95% CI: 1.14–1.56), CH (OR: 1.63, 95% CI: 1.21–2.19), and PE (OR: 1.68, 95% CI: 1.27–2.21) than those who consumed breakfast daily. No association was found between skipping breakfast and the risk of developing GH (OR: 1.26, 95% CI: 0.99–1.61) and SuPE (OR: 0.91, 95% CI: 0.55–1.49). Stratified analysis showed that the risk of developing HDP due to skipping breakfast was highest in the group with the highest daily energy intake. Conclusions Skipping breakfast during pre-to early pregnancy is associated with the development of HDP. Further longitudinal studies are required to clarify the causal association between skipping breakfast and HDP.

The first cell fate commitment during mammalian development is the specification of the inner cell mass and trophectoderm. This irreversible cell fate commitment should be epigenetically regulated, but the precise mechanism is largely unknown in humans. Here, we show that naïve human embryonic stem (hES) cells can transdifferentiate into trophoblast stem (hTS) cells, but primed hES cells cannot. Our transcriptome and methylome analyses reveal that a primate-specific miRNA cluster on chromosome 19 (C19MC) is active in naïve hES cells but epigenetically silenced in primed ones. Moreover, genome and epigenome editing using CRISPR/Cas systems demonstrate that C19MC is essential for hTS cell maintenance and C19MC-reactivated primed hES cells can give rise to hTS cells. Thus, we reveal that C19MC activation confers differentiation potential into trophoblast lineages on hES cells. Our findings are fundamental to understanding the epigenetic regulation of human early development and pluripotency.

Personality has been shown to predict postpartum depressive symptoms (PDS) assessed by the Edinburgh Postnatal Depression Scale (EPDS). However, existing studies have not considered the underlying symptom dimensions in the EPDS. We analyzed data from 15,012 women who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Personality was assessed in middle pregnancy using the short-form Eysenck Personality Questionnaire-Revised. PDS were defined as EPDS score ≥ 9 at 1 month after delivery. The EPDS items were further divided into three dimensions: depressed mood, anxiety, and anhedonia. Multiple analyses were conducted to examine the associations of each personality scale with PDS and three dimensions in the EPDS, adjusting for age, parity, mode of delivery, education, income, and social isolation. The prevalence of PDS assessed by the EPDS at 1 month after delivery was 13.1%. Higher neuroticism scores were associated with PDS (odds ratio [OR], 2.63; 95% confidence interval [CI], 2.48 to 2.79) and all three dimensions (all p p p p = 0.20) or anhedonia (p = 0.92). In conclusion, higher neuroticism and lower extraversion were associated with PDS and the three underlying dimensions in the EPDS, while lower psychoticism was associated with anxiety, but not with depressed mood or anhedonia.

Natural disasters can have serious mental health consequences. We aimed to examine the long-term effects of the 2011 Great East Japan Earthquake (GEJE) on postpartum depressive symptoms (PDS).The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study recruited pregnant women in Miyagi Prefecture from 2013 to 2016. Data from 11,403 participants were used in this study. Women were asked about their traumatic experiences of the GEJE with questions addressing threat, witness, and loss. PDS were defined as Edinburgh Postnatal Depression Scale score ≥9 at 1 month after delivery. Multiple logistic regression analyses were conducted to examine the associations of different traumatic experiences of the GEJE and number of traumatic experiences with PDS, after adjustment for age, parity, feelings toward pregnancy, education, income, social isolation, house damage caused by the GEJE, and survey year.About two-fifths of women had at least one traumatic experience of the GEJE. The prevalence of PDS at 1 month after delivery was 13.3 %. Life-threatening experience and witnessing another person's actual or threatened death were associated with PDS: the odds ratios (ORs) were 1.40 (95 % confidence interval [CI], 1.24-1.59) and 1.28 (95 % CI, 1.08-1.53), respectively. Loss of close person was not associated with PDS: the OR was 1.13 (95 % CI, 0.99-1.30). Larger number of traumatic experiences of the GEJE was associated with increased risk of PDS (p for trend0.001).PDS was self-reported.Traumatic experiences of the GEJE prior to pregnancy were associated with increased risks of PDS.

Background Childcare facilities have been reported as a factor in lowering the association of postnatal psychiatric symptoms with children's behavior problems; however, no studies have considered prenatal psychiatric symptoms. This study aimed to examine whether the use of childcare facilities moderates the association of maternal psychological distress in the prenatal and postnatal periods with behavior problems in children. Methods The present study was based on the data from 23,130 mother-child pairs participating in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. We used the K6 to assess and divide maternal psychological distress in early pregnancy and two years postpartum into four categories: none in both prenatal and postnatal periods (none), only the prenatal period (prenatal only); only the postnatal period (postnatal only); both prenatal and postnatal periods (both). The children's behavior problems were assessed using the Child Behavior Checklist for Ages 1½-5 (CBCL) at four years of age. The clinical range of the externalizing, internalizing, and total problem scales of the CBCL was defined as having behavior problems. To examine whether the use of childcare facilities moderates the association between maternal psychological distress and children's behavior problems, we conducted a stratified analysis based on the use of childcare facilities or not at two years old. In addition, the interaction term between maternal psychological distress and the use of childcare facilities was included as a covariate in the multivariate logistic regression analysis to confirm the p-value for interaction. Results The prevalence of the clinical ranges of externalizing problems, internalizing problems, and clinical range of total problems were 13.7%, 15.4%, and 5.8%, respectively. The association of maternal psychological distress with a high risk of children's behavior problems was significant, except a significant association was not identified between prenatal only psychological distress and externalizing problems in the group that did not use childcare facilities. In addition, interactions between the use of childcare facilities and maternal psychological distress on behavioral problems in children were not significant. Conclusions The use of childcare facilities did not moderate the association of maternal psychological distress in prenatal and postnatal periods with behavior problems in children.

The COVID-19 pandemic has exposed several inequalities worldwide, including the populations' access to healthcare systems and economic differences that impact the access to vaccination, medical resources, and health care services. Scientific research activities were not an exception, such that scientific research was profoundly impacted globally. Research trainees and early career researchers (ECRs) are the life force of scientific discovery around the world, and their work and progress in research was dramatically affected by the COVID-19 pandemic. ECRs are a particularly vulnerable group as they are in a formative stage of their scientific careers, any disruptions during which is going to likely impact their lifelong career trajectory. To understand how COVID-19 impacted lives, career development plans, and research of Developmental Origins of Health and Disease (DOHaD) ECRs, the International DOHaD ECR committee formed a special interest group comprising of ECR representatives of International DOHaD affiliated Societies/Chapters from around the world (Australia and New Zealand, Canada, French Speaking DOHaD, Japan, Latin America, Pakistan and USA). The anecdotal evidence summarized in this brief report, provide an overview of the findings of this special interest group, specifically on the impact of the evolving COVID-19 pandemic on daily research activities and its effects on career development plans of ECRs. We also discuss how our learnings from these shared experiences can strengthen collaborative work for the current and future generation of scientists.

Background Childcare facilities are a factor that lowers the established association of mother’s postnatal psychiatric symptoms with children's behavioral problems. However, no studies have considered the prenatal psychiatric symptoms yet. This study examined whether the use of childcare facilities moderates the association of maternal psychological distress in early pregnancy and at two years postpartum with behavioral problems in children aged four years. Methods The present study was based on the data from 23,130 mother–child pairs participating in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. K6 was used to classify maternal psychological distress in early pregnancy and at two years postpartum into four categories: none in both prenatal and postnatal periods (none), only the prenatal period (prenatal only); only the postnatal period (postnatal only); both prenatal and postnatal periods (both). The children's behavioral problems were assessed using the Child Behavior Checklist for Ages 1½–5 (CBCL) aged four years. The clinical range of the externalizing, internalizing, and total problem scales of the CBCL was defined as having behavioral problems. To examine whether availing childcare facilities moderates the association between maternal psychological distress and children's behavioral problems, we conducted a stratified analysis based on the use of childcare facilities or not, at two years of age. The interaction term between maternal psychological distress and use of childcare facilities was included as a covariate in the multivariate logistic regression analysis to confirm the p-value for the interaction. Results The prevalence of the clinical ranges of externalizing problems, internalizing problems, and clinical range of total problems were 13.7%, 15.4%, and 5.8%, respectively. The association of maternal psychological distress with a high risk of children's behavioral problems was significant; however, the association between prenatal only psychological distress and externalizing problems in the group that did not use childcare facilities was not significant. Interactions between the use of childcare facilities and maternal psychological distress on behavioral problems in children were not significant. Conclusions Use of childcare facilities did not moderate the association of maternal psychological distress in early pregnancy and at two years postpartum with behavioral problems in children aged four years.

To estimate the prevalence of insomnia and examine the association between social isolation and insomnia among pregnant women.This cross-sectional study was part of the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study from 2013 to 2017. Pregnant women were recruited at obstetric clinics and hospitals in Miyagi Prefecture, Japan. We analyzed 17,586 women who completed the questionnaires and were allowed to transcribe medical records. Insomnia was defined as the Athens Insomnia Scale score of ≥6. The Lubben Social Network Scale-abbreviated version was used to assess social isolation (defined as scores12), and its subscales were used to assess marginal family ties and marginal friendship ties. Multiple logistic regression analyses were conducted to examine the association between social isolation and insomnia during pregnancy, adjusting for age, parity, prepregnancy body mass index, feelings toward pregnancy, education, income, work status, morning sickness, and psychological distress. Multiple logistic regression analyses were also conducted for marginal family ties and marginal friendship ties.The prevalence of insomnia in the second trimester was 37.3%. Women who were socially isolated were more likely to have insomnia than women who were socially integrated: the multivariate-adjusted odds ratio (OR) was 1.26 (95% confidence interval [CI], 1.16-1.36). Marginal family ties and marginal friendship ties were also associated with increased risks of insomnia: the multivariate-adjusted ORs were 1.40 (95% CI, 1.25-1.56) and 1.15 (95% CI, 1.07-1.24), respectively.Social isolation from family and friends was associated with increased risks of insomnia among pregnant women.

Genomic imprinting (GI) is a mammalian-specific epigenetic phenomenon that has been implicated in the evolution of the placenta in mammals.Embryo transfer procedures and trophoblast stem (TS) cells were used to re-examine mouse placenta-specific GI genes. For the analysis of human GI genes, cytotrophoblast cells isolated from human placental tissues were used. Using human TS cells, the biological roles of human GI genes were examined.(1) Many previously identified mouse GI genes were likely to be falsely identified due to contaminating maternal cells. (2) Human placenta-specific GI genes were comprehensively determined, highlighting incomplete erasure of germline DNA methylation in the human placenta. (3) Human TS cells retained normal GI patterns. (4) Complete hydatidiform mole-derived TS cells were characterized by aberrant GI and enhanced trophoblastic proliferation. The maternally expressed imprinted gene p57KIP2 may be responsible for the enhanced proliferation. (5) The primate-specific microRNA cluster on chromosome 19, which is a placenta-specific GI gene, is essential for self-renewal and differentiation of human TS cells.Genomic imprinting plays diverse and important roles in human placentation. Experimental analyses using TS cells suggest that the GI maintenance is necessary for normal placental development in humans.

ImportancePeripartum suicide attempt is a major psychiatric complication associated with pregnancy, but the risk factors remain largely uncertain.ObjectiveTo identify the demographic characteristics and predisposing risks for peripartum suicide attempts and postpartum depression.Design, Setting, and ParticipantsThis cohort study used retrospective data on pregnant women who delivered children between April 1, 2016, and March 31, 2021, at 712 hospitals in Japan. The nationwide Diagnosis Procedure Combination database was used.ExposuresPsychiatric and nonpsychiatric medical history, age, alcohol and tobacco use, and obstetric complications and procedures.Main Outcomes and MeasuresData on admissions for prepartum suicide attempt and delivery during the same hospital stay and readmissions for depression or suicide attempt within 1 year post partum were collected. Comparisons of prevalence of each study variable were performed, and multivariable logistic regression analyses were used to determine risk factors.ResultsFrom a total of 39 908 649 hospitalization episodes, 804 617 cumulative pregnant women (median [IQR] age at childbirth, 33 [29-36] years) who delivered at the enrolled hospitals were identified, including 1202 who were admitted for suicide attempt and delivery during the same hospital stay and 111 readmitted for suicide attempt within 1 year post partum. Risk factors associated with prepartum suicide attempts included younger age (adjusted odds ratio [aOR], 0.99; 95% CI, 0.98-1.00) and histories of personality disorder (aOR, 10.81; 95% CI, 5.70-20.49), depression (aOR, 3.97; 95% CI, 2.35-6.70), schizophrenia (aOR, 2.89; 95% CI, 1.52-5.50), and adjustment disorder (aOR, 2.66; 95% CI, 1.07-6.58). Risk factors associated with postpartum suicide attempts included younger age (aOR, 0.96; 95% CI, 0.93-1.00), heavy tobacco use (aOR, 23.09; 95% CI, 5.46-97.62), and histories of alcohol use disorder (aOR, 163.54; 95% CI, 28.30-944.95), personality disorder (aOR, 10.28; 95% CI, 3.29-32.10), anxiety disorders (aOR, 8.13; 95% CI, 2.88-22.98), depression (aOR, 7.27; 95% CI, 2.95-17.91), schizophrenia (aOR, 5.77; 95% CI, 2.17-15.38), bipolar disorder (aOR, 3.98; 95% CI, 1.36-11.67), and insomnia (aOR, 3.17; 95% CI, 1.30-7.78). On sensitivity analysis, risk factors associated with postpartum depression after excluding those with prenatal depression included histories of personality disorder, adjustment disorder, bipolar disorder, insomnia, and anxiety disorders.Conclusions and RelevanceThe findings of this cohort study suggest that histories of smoking and prenatal psychiatric disorders are potential risk factors for peripartum suicide attempts and may require additional treatment and prevention interventions.

Background Although small for gestational age (SGA) is a serious problem worldwide, the association of dietary patterns before and during pregnancy with SGA risk is unclear. We evaluated this association among Japanese pregnant women using three methods: reduced rank regression (RRR) and partial least squares (PLS), methods for extracting dietary patterns that can explain the variation of response variables, and principal component analysis (PCA), a method for extracting dietary patterns of the population. Methods Between July 2013 and March 2017, 22,493 pregnant women were recruited to the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, a population-based prospective birth cohort study in Japan. Information on dietary intake was obtained using food frequency questionnaires, and dietary patterns were extracted using RRR, PLS, and PCA. Information on birth weight was obtained from obstetric records, and the birth weight SD score and SGA were defined by the method of the Japan Pediatric Society. The associations of dietary patterns with birth weight SD score and SGA risk were investigated using multiple linear regression and multiple logistic regression, respectively. Results A total of 17,728 mother-child pairs were included. The birth weight SD score was 0.15 ± 0.96, and the prevalence of SGA was 6.3%. The dietary patterns extracted by RRR and PLS were similar and characterized by a high intake of cereals and fruits and a low intake of alcoholic and non-alcoholic beverages in both pre- to early pregnancy and from early to mid-pregnancy. Higher adoption of the RRR and PLS patterns in both periods was associated with an increased birth weight SD score and lower risk of SGA. In contrast, the PCA1 pattern was not associated with birth weight SD score or SGA risk in either period. Although the PCA2 pattern was associated with increased birth weight SD score from early to mid-pregnancy, no other associations with birth weight SD score or SGA risk were observed. Conclusions The dietary pattern with a high intake of cereals and fruits and a low intake of alcoholic and non-alcoholic beverages before and during pregnancy was associated with a decreased SGA risk in Japan.

COVID-19 is associated with increased incidence of preterm birth (PTB). We assessed pathways by which SARS-CoV-2 could access the placenta. Placentae, from PTB with or without chorioamnionitis (ChA), or from term pregnancies (n = 12/13/group) were collected. Peripheral blood was collected from healthy pregnant women (n = 6). Second trimester placental explants (16–20 weeks, n = 5/group) were treated with lipopolysaccharide (LPS, to mimic bacterial infection) and ACE2, CCL2, IL-6/8 and TNFα mRNA was assessed. ChA-placentae exhibited increased ACE2 and CCL2 mRNA expression (p &lt, 0.05). LPS increased cytokine and ACE2 mRNA in placental explants. Placental ACE2 protein localized to syncytiotrophoblast, fetal endothelium, extravillous trophoblast and in immune cells-subsets (M1/M2 macrophage and neutrophils) within the villous stroma. Significantly increased numbers of M1 macrophage and neutrophils were present in the ChA-placenta (p &lt, 0.001). Subsets of peripheral immune cells from pregnant women express the ACE2 mRNA and protein. A greater fraction of granulocytes was positive for ACE2 protein expression compared to lymphocytes or monocytes. These data suggest that in pregnancies complicated by ChA, ACE2 positive immune cells in the maternal circulation have the potential to traffic SARS-CoV-2 virus to the placenta and increase the risk of vertical transmission to the placenta/fetus.

Objective: To survey the frequency and risk factors for father-to-infant lack of affection (LA) and anger/rejection (AR) bonding failure at 1 month postpartum.Material and methods: The study partic...

BACKGROUND: Although there is some evidence that severe acute respiratory syndrome coronavirus 2 can invade the human placenta, limited data exist on the gestational age-dependent expression profile of the severe acute respiratory syndrome coronavirus 2 cell entry mediators, angiotensin-converting enzyme 2 and transmembrane protease serine 2, at the human maternal-fetal interface. There is also no information as to whether the expression of these mediators is altered in pregnancies complicated by preeclampsia or preterm birth. This is important because the expression of decidual and placental angiotensin-converting enzyme 2 and transmembrane protease serine 2 across gestation may affect the susceptibility of pregnancies to vertical transmission of severe acute respiratory syndrome coronavirus 2. OBJECTIVE: This study aimed to investigate the expression pattern of specific severe acute respiratory syndrome coronavirus 2 cell entry genes, angiotensin-converting enzyme 2 and transmembrane protease serine 2, in the placenta across human pregnancy and in paired samples of decidua and placenta in pregnancies complicated by preterm birth or preeclampsia compared with those in term uncomplicated pregnancies. STUDY DESIGN: In this study, 2 separate cohorts of patients, totaling 87 pregnancies, were included. The first cohort was composed of placentae from first- (7-9 weeks), second- (16-18 weeks), and third-trimester preterm (26-31 weeks) and third-trimester term (38-41 weeks) pregnancies (n=5/group), whereas the second independent cohort included matched decidua and placentae from pregnancies from term uncomplicated pregnancies (37-41 weeks' gestation; n=14) and pregnancies complicated by preterm birth (26-37 weeks' gestation; n=11) or preeclampsia (25-37 weeks' gestation; n=42). Samples were subjected to quantitative polymerase chain reaction and next-generation sequencing or RNA sequencing for next-generation RNA sequencing for angiotensin-converting enzyme 2 and transmembrane protease serine 2 mRNA expression quantification, respectively. RESULTS: In the first cohort, angiotensin-converting enzyme 2 and transmembrane protease serine 2, exhibited a gestational age-dependent expression profile, that is, angiotensin-converting enzyme 2 and transmembrane protease serine 2 mRNA was higher (P

COVID-19 infection during pregnancy is associated with an increased incidence of preterm birth but neonatal infection is rare. We assessed pathways by which SARS-CoV-2 could access the placenta and contribute to fetal transmission. Placentas from pregnancies complicated with chorioamnionitis (ChA), exhibited increased expression of ACE2 mRNA. Treatment of 2nd trimester placental explants with LPS, induced an acute increase in cytokine expression followed by ACE2 mRNA. Placental ACE2 protein localized to syncytiotrophoblast, in fetal blood vessels and M1/M2 macrophage and neutrophils within the villous stroma. Increased numbers of M1 macrophage and neutrophils were present in the placenta of ChA pregnancies. Maternal peripheral immune cells (mainly granulocytes and monocytes) express the ACE2 mRNA and protein. These data suggest that in COVID19 positive pregnancies complicated by ChA, ACE2 positive immune cells have the potential to traffic SARS-CoV-2 virus to the placenta and increase the risk of vertical transmission to the placenta/fetus.

The mechanisms by which the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) induces neurological complications remain to be elucidated. We aimed to identify possible effects of hypoxia on the expression of SARS-CoV-2 cell entry mediators, angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane protease serine 2 (TMPRSS2) protein, in human brain endothelial cells, in vitro. hCMEC/D3 cells were exposed to different oxygen tensions: 20% (Control group), 8% or 2% O2 (Hypoxia groups). Cells were harvested 6-, 24- and 48 h following hypoxic challenge for assessment of mRNA and protein, using qPCR and Western Blot. The response of the brain endothelial cells to hypoxia was replicated using modular incubator chambers. We observed an acute increase (6 h, p

DNA methylation is globally reprogrammed after fertilization, and as a result, the parental genomes have similar DNA-methylation profiles after implantation except at the germline differentially methylated regions (gDMRs). We and others have previously shown that human blastocysts might contain thousands of transient maternally methylated gDMRs (transient mDMRs), whose maternal methylation is lost in embryonic tissues after implantation. In this study, we performed genome-wide allelic DNA methylation analyses of purified trophoblast cells from human placentas and, surprisingly, found that more than one-quarter of the transient-in-embryo mDMRs maintained their maternally biased DNA methylation. RNA-sequencing-based allelic expression analyses revealed that some of the placenta-specific mDMRs were associated with expression of imprinted genes (e.g., TIGAR, SLC4A7, PROSER2-AS1, and KLHDC10), and three imprinted gene clusters were identified. This approach also identified some X-linked gDMRs. Comparisons of the data with those from other mammals revealed that genomic imprinting in the placenta is highly variable. These findings highlight the incomplete erasure of germline DNA methylation in the human placenta; understanding this erasure is important for understanding normal placental development and the pathogenesis of developmental disorders with imprinting effects.

Objective: To survey prevalence and risk factors for paternal postpartum depression symptoms at one and 6 months postpartum in Japan.Material and methods: The study participants enrolled in the pro...

Parental exposure to stress or glucocorticoids either before or during pregnancy can have profound influences on neurodevelopment, neuroendocrine function and behaviours in offspring. Specific outcomes are dependent on the nature, intensity and timing of the exposure, as well as species, sex and age of the subject. Most recently, it has become evident that outcomes are not confined to first-generation offspring and that there may be intergenerational and transgenerational transmission of effects. There has been intense focus on the mechanisms by which such early exposure leads to long-term and potential transgenerational outcomes, and there is strong emerging evidence that epigenetic processes (histone modifications, DNA methylation, and small non-coding RNAs) are involved. New knowledge in this area may allow the development of interventions that can prevent, ameliorate or reverse the long-term negative outcomes associated with exposure to early adversity. This review will focus on the latest research, bridging human and pre-clinical studies, and will highlight some of the limitations, challenges and gaps that exist in the field.

The most common form of male infertility is a low sperm count, known as oligozoospermia. Studies suggest that oligozoospermia is associated with epigenetic alterations. Epigenetic alterations in sperm, which may arise due to the exposure of gametes to environmental factors or those that pre-exist in the sperm of infertile individuals, may contribute to the increased incidence of normally rare imprinting disorders in babies conceived after assisted reproductive technology using the sperm of infertile men. Genomic imprinting is an important developmental process whereby the allelic activity of certain genes is regulated by DNA methylation established during gametogenesis. The aberrant expression of several imprinted genes has been linked to various diseases, malignant tumors, lifestyle and mental disorders in humans. Understanding how infertility and environmental factors such as reproductive toxicants, certain foods, and drug exposures during gametogenesis contribute to the origins of these disorders via defects in sperm is of paramount importance. In this review, we discuss the association of epigenetic alterations with abnormal spermatogenesis and the evidence that epigenetic processes, including those required for genomic imprinting, may be sensitive to environmental exposures during gametogenesis, fertilization and early embryonic development. In addition, we review imprinting diseases and their relationships with environmental factors. While the plasticity of epigenetic marks may make these more susceptible to modification by the environment, this also suggests that aberrant epigenetic marks may be reversible. A greater understanding of this process and the function of epidrugs may lead to the development of new treatment methods for many adult diseases in the future.

Purpose – This study is concerned with the direct numerical simulation (DNS) of a turbulent channel flow by an improved vortex in cell (VIC) method. The paper aims to discuss these issues. Design/methodology/approach – First, two improvements for VIC method are proposed to heighten the numerical accuracy and efficiency. A discretization method employing a staggered grid is presented to ensure the consistency among the discretized equations as well as to prevent the numerical oscillation of the solution. A correction method for vorticity is also proposed to compute the vorticity field satisfying the solenoidal condition. Second, the DNS for a turbulent channel flow is conducted by the improved VIC method. The Reynolds number based on the friction velocity and the channel half width is 180. Findings – It is highlighted that the simulated turbulence statistics, such as the mean velocity, the Reynolds shear stress and the budget of the mean enstrophy, agree well with the existing DNS results. It is also shown that the organized flow structures in the near-wall region, such as the streaks and the streamwise vortices, are favourably captured. These demonstrate the high applicability of the improved VIC method to the DNS for wall turbulent flows. Originality/value – This study enables the VIC method to perform the DNS for wall turbulent flows.

Direct numerical simulation (DNS) of a fully-developed turbulent flow in a channel rotating around the span- wise axis is performed. A vortex in cell (VIC) method, of which numerical accuracy was successfully improved by the authors in their prior study, is applied to the DNS. The Reynolds number based on the friction velocity and the channel half width is 171, and the nondimensional rotation number defined with the channel angular velocity and width is 2.1. The simulated turbulence statistics, such as the mean velocity and the Reynolds shear stress, are favorably compared with the existing DNS results. The simulation can analyze the disappearance of the streak structures near the suction-wall due to the channel rotation. It also captures the secondary flow of the Taylor-Gortler vortex pattern near the pressure-wall. These simulation results demonstrate that the VIC method improved by the authors is indeed applicable to the DNS of turbulent flows in rotating channel.

As a part of the study on the jet diffusion, the jet flow issuing from a circular pipe with the fluttering fins made of the artificial cellulose has been investigated. In this paper, the turbulent characteristics of this flow field were examined from the velocity information obtained by the high-speed PIV method. The experiment was carried out without the fins and with the fins having various lengths. As a result, it has been found that the turbulence is enhanced in the jet flow due to the fin oscillation and a large scale fluctuation appears with the increase of the fin length. From the results of the auto-correlation it has been clarified that the turbulent structure contained in the jet flow was destroyed by attaching the fins near the outer edge of the jet flow. Furthermore, from the continuous wavelet transform analysis of the fluctuating velocities, it has been recognized that the jet flow tends to contain the lower frequency with the increase of the fin length.

症例は慢性C型肝炎の既往を有する68歳の男性で, 2006年1月頃より弛張熱と右側胸部痛が出現し近医を受診した. 腹部超音波検査で肝右葉に6センチ大の腫瘤を指摘され当院へ紹介となった. 腹部CTでは肝後区域に直径6センチのring enhancementを有する単発性腫瘤を認めた. 肝膿瘍と診断し経皮経肝膿瘍ドレナージを施行, 灰白色の膿汁を排出した. ドレナージ後も炎症反応高値が遷延したため, 経皮的治療の限界と判断し肝部分切除術を施行した. 術後の病理組織学的検査では異型性を伴う類円形～短紡錘形の腫瘍細胞が充実性に増殖しており, 免疫組織染色ではVimentinとMIB-1に強陽性を示し, かつ鍍銀染色では索状配列が保持されていた. なかでも, MIB-1標識率は80%を越え, 強い増殖能を有することをうかがわせた. 以上より, C型肝炎を背景に発生した肉腫様肝癌と診断した. 未治療の肝腫瘍, とりわけ肉腫様肝癌が肝膿瘍として発症することは極めてまれであり, 考察を加えて報告する.

Candida dubliniensis is rare and very similar to C. albicans. To date, detailed clinical reports on C. dubuliniensis recovered from an immunocompromised patient have not been described in Japan. A 71-year-old man with end-stage liver cirrhosis had been treated for suppurative omarthritis due to methicillin-resistant Staphylococcus aureus (MRSA). Anti-MRSA agents and broad-spectrum antimicrobials but no antifungal agents had been administrated. C. dubliniensis, isolated from the sputum, was eliminated by selective digestive decontamination and supportive therapy. This case emphasizes the need to recognize this emerging Candida sp., C. dubliniensis in cases of opportunistic infection.

The most common form of male infertility is a low sperm count, known as oligozoospermia. Studies suggest that oligozoospermia is associated with epigenetic alterations. Epigenetic alterations in sperm, which may arise due to the exposure of gametes to environmental factors or those that pre-exist in the sperm of infertile individuals, may contribute to the increased incidence of normally rare imprinting disorders in babies conceived after assisted reproductive technology using the sperm of infertile men. Genomic imprinting is an important developmental process whereby the allelic activity of certain genes is regulated by DNA methylation established during gametogenesis. The aberrant expression of several imprinted genes has been linked to various diseases, malignant tumors, lifestyle and mental disorders in humans. Understanding how infertility and environmental factors such as reproductive toxicants, certain foods, and drug exposures during gametogenesis contribute to the origins of these disorders via defects in sperm is of paramount importance. In this review, we discuss the association of epigenetic alterations with abnormal spermatogenesis and the evidence that epigenetic processes, including those required for genomic imprinting, may be sensitive to environmental exposures during gametogenesis, fertilization and early embryonic development. In addition, we review imprinting diseases and their relationships with environmental factors. While the plasticity of epigenetic marks may make these more susceptible to modification by the environment, this also suggests that aberrant epigenetic marks may be reversible. A greater understanding of this process and the function of epidrugs may lead to the development of new treatment methods for many adult diseases in the future.

DNA methylation is globally reprogrammed during mammalian preimplantation development, which is critical for normal development. Recent reduced representation bisulfite sequencing (RRBS) studies suggest that the methylome dynamics are essentially conserved between human and mouse early embryos. RRBS is known to cover 5–10% of all genomic CpGs, favoring those contained within CpG-rich regions. To obtain an unbiased and more complete representation of the methylome during early human development, we performed whole genome bisulfite sequencing of human gametes and blastocysts that covered>70% of all genomic CpGs. We found that the maternal genome was demethylated to a much lesser extent in human blastocysts than in mouse blastocysts, which could contribute to an increased number of imprinted differentially methylated regions in the human genome. Global demethylation of the paternal genome was confirmed, but SINE-VNTR-Alu elements and some other tandem repeat-containing regions were found to be specifically protected from this global demethylation. Furthermore, centromeric satellite repeats were hypermethylated in human oocytes but not in mouse oocytes, which might be explained by differential expression of de novo DNA methyltransferases. These data highlight both conserved and species-specific regulation of DNA methylation during early mammalian development. Our work provides further information critical for understanding the epigenetic processes underlying differentiation and pluripotency during early human development., Author Summary DNA methylation reprogramming after fertilization is critical for normal mammalian development. Early embryos are sensitive to environmental stresses and a number of reports have pointed out the increased risk of DNA methylation errors associated with assisted reproduction technologies. Therefore, it is very important to understand normal DNA methylation patterns during early human development. Recent reduced representation bisulfite sequencing studies reported partial methylomes of human gametes and early embryos. To provide a more comprehensive view of DNA methylation dynamics during early human development, we report on whole genome bisulfite sequencing of human gametes and blastocysts. We show that the paternal genome is globally demethylated in blastocysts whereas the maternal genome is demethylated to a much lesser extent. We also reveal unique regulation of imprinted differentially methylated regions, gene bodies and repeat sequences during early human development. Our high-resolution methylome maps are essential to understand epigenetic reprogramming by human oocytes and will aid in the preimplantation epigenetic diagnosis of human embryos.

Cardioreversion of ventricular fibrillation (VF) is one of the major targets in the therapeutic strategy for cardiac arrest. We report a case in whom intra-aortic balloon pumping (IABP) effectively treated VF caused by submersion and in whom the neurological outcome was relatively good. An 18-year-old man drowned after diving into a swimming pool. When he was rescued after 12 minutes, he was in cardiac arrest. We started advanced cardiovascular life support just after his arrival at our emergency and critical care center. The electrocardiogram revealed VF. Despite applications of direct current defibrillation and administration of vasopressin and nifecarant, VF occurred repeatedly. After we started IABP, his cardiac rhythm and vital signs stabilized. X-ray examinations revealed a cervical spine injury and severe pulmonary edema. Normothermia therapy and IABP support were performed, and high dose methylprednisolone therapy was also carried out for the cervical spine injury. Under this intensive care regimen, the patient's status improved. His Glasgow outcome scale was severe disability on discharge from our hospital. We believe that IABP is one of the effective therapies in a patient with intractable cardiac arrhythmia. In addition, IABP may be effective for maintenance of cerebral blood flow after cardiopulmonary resuscitation.

Through 1996 into 1997, a spot investigation on mercury contamination was conducted three times in Tanzania, especially around the Lake Victoria. A total of 150 goldminers, 103 fishermen and their families, and 19 residents of Mwanza City volunteered for the current study. A high total mercury level of 48.3 ppm (near to 50 ppm, a critical level of Minamata disease) and over in the head hair was observed in six goldminers (highest value, 953 ppm), four fishermen and their families (highest value, 416 ppm), and four Mwanza people (highest value, 474 ppm). With the exception of these 14 subjects, however, each mean total mercury level was well within the normal range (below 10 ppm). Out of the goldminers examined, 14 cases were diagnosed as a mild form of inorganic-mercury poisoning according to their clinical symptoms (such as polyneuropathy mercurialis, neuroasthemia, or tremor mercurialis) and the low ratio of methylmercury to total mercury, whereas neither inorganic-mercury poisoning nor methylmercury poisoning (Minamata disease) was noted in the fishermen and their families or in the Mwanza people. In addition, some subjects who showed a high total mercury level made habitual use of toilet soap containing much mercury. The findings obtained suggest that the mercury pollution in Tanzania is not very serious, however, it should be observed continuously.

Aims To determine whether treating mild gestational diabetes mellitus (GDM) is associated with improvement of pregnancy outcomes in Japan. Methods In a multi-institutional retrospective study, we examined pregnant women meeting the criteria for mild GDM (i.e., only one abnormal value [OAV] for 75-g OGTT; fasting glucose ≥100 mg/dL, 1-h postprandial glucose ≥180 mg/dL, and 2-h postprandial glucose ≥150 mg/dL), receiving either routine prenatal care (non-treatment group) or dietary intervention alone or dietary intervention with self-monitoring of blood glucose and/or insulin therapy, if necessary (treatment group). Pregnancy outcomes were compared between these groups. Results Data from 893 eligible women were collected from 30 institutions. Participants included 542 untreated and 351 treated women. Although there were no significant differences in baseline clinical characteristics or maternal and perinatal outcomes between these groups, the incidence of large-for-gestational-age (LGA) infants was lower in the treatment group ( P = 0.07). Multiple logistic regression analysis (MLRA) revealed that pre-pregnancy BMI and gestational weight gain were associated with LGA infants, while 75-g OGTT results were unrelated to LGA. When overweight and obese women were the subjects, the number of LGA infants was significantly lower in the intervention than in the control group, and gestational weight gain was significantly lower in the treatment than in the control group. MLRA showed that intervention was significantly related to a lower incidence of LGA infants. Conclusions Our study suggests that maternal BMI impacts fetal growth and that treatment for overweight or obese mothers with OAV is associated with a lower frequency of LGA infants.