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New findings What is the central question of this study? Does treatment of hypoxic dams with a placenta-targeted antioxidant prevent the release of placenta-derived factors that impair maturation or growth of fetal cardiomyocytes in vitro? What is the main finding and its importance? Factors released from hypoxic placentae impaired fetal cardiomyocyte maturation (induced terminal differentiation) and growth (increased cell size) in vitro, which was prevented by maternal treatment with a placenta-targeted antioxidant (nMitoQ). Moreover, there were no sex differences in the effects of placental factors on fetal cardiomyocyte maturation and growth. Overall, our data suggest that treatment targeted against placental oxidative stress could prevent fetal programming of cardiac diseases via the release of placental factors. Abstract Pregnancy complications associated with placental oxidative stress may impair fetal organ development through the release of placenta-derived factors into the fetal circulation. We assessed the effect of factors secreted from placentae previously exposed to prenatal hypoxia on fetal cardiomyocyte development and developed a treatment strategy that targets placental oxidative stress by encapsulating the antioxidant MitoQ into nanoparticles (nMitoQ). We used a rat model of prenatal hypoxia (gestational day (GD) 15-21), which was treated with saline or nMitoQ on GD15. On GD21, placentae were harvested, placed in culture, and conditioned medium (containing placenta-derived factors) was collected after 24 h. This conditioned medium was then added to cultured cardiomyocytes from control dam fetuses. Conditioned medium from prenatally hypoxic placentae increased the percentage of binucleated cardiomyocytes (marker of terminal differentiation) and the size of mononucleated and binucleated cardiomyocytes (sign of hypertrophy), effects that were prevented by nMitoQ treatment. Our data suggest that factors derived from placentae previously exposed to prenatal hypoxia lead to abnormal fetal cardiomyocyte development, and show that treatment against placental oxidative stress may prevent fetal programming of cardiac disease.

Coronavirus disease 2019 is a contagious infection that caused a global lockdown and affected children who needed to stay home. There is a lack of knowledge about the role of parental stress and physical environment design on children’s mental wellbeing in quarantine. We hypothesis that COVID-19 quarantine affected child mental health, and that paternal stress or support, and child physical environment including household space, colors, sunlight exposure, and natural views, impacted child mental wellbeing in the quarantine. To assess the effect of quarantine on a child’s mental health, an online survey was administered globally through scientific organizations and social media. Those over 18 years old, and guardians of children were asked to participate in the survey. The survey was filled by 114 guardians from 31 countries. Descriptive statistics were used to summarize the data. Most participants experienced stress in the quarantine and reported child anxiety symptoms including focus reduction, sleeping difficulties, and appetite changes. Family fun activities and encouraging words, were mostly successful in reducing child anxiety. Reporting anxiety symptoms in children were more common in parents who had mental hardships compared to those who did not experience mental problems or had an improved mental status. Physical environment assessment showed that households with bright walls associated with fewer reports of child mental problems compared to households with neutral wall colors, and that most guardians thought that their children’s living space was not sufficient to play and study. Architects can provide evidence-based recommendations for customers to support children’s mental health.

Objectives: To perform a systematic study about the contribution of architecture and interior design researchers in studying the effect of physical environment on mental disorders. Background: Mental disorders are a major health problem worldwide and related to severe distress, functional disabilities, and heavy economical burdens. Studies propose that physical environment design can trigger or reduce mental disorder symptoms. However, there is a lack of knowledge about the extent of architectural design research contribution to all types of mental disorder prevention or intervention. Methods: A team of cross-disciplinary researchers gathered information from peer-reviewed manuscripts about the effect of architectural design on enhancing or reducing mental disorder symptoms. Data were collected from manuscripts published between 2008 and 2020 (research related to the topic became clearer in quality and quantity then). Keywords including architecture, interior design, physical environment, and mental disorders were used in the systematic search. Databases were collected using online resources. Numerical data collected from quantitative studies were organized in tables. Results: Our data showed that there were a lot of studies about dementia and autism; few studies about schizophrenia, anxiety, stress-related disorders, and depressive disorders; and no studies about the rest of the mental disorders. General environment followed by housing facility design were the most assessed physical environments for mental disorders. Conclusions: As all mental disorders can have a significant impact on the society, we conclude that architectural studies should focus more on improving or preventing the symptoms of all types of mental disorders through the design of physical environments.

Intrauterine growth restriction (IUGR, a pregnancy complication where the fetus does not reach its genetic growth potential) is a leading cause of fetal morbidity and mortality with a significant impact on population health. IUGR is associated with gestational hypoxia; which can lead to placental oxidative stress and fetal programming of cardiovascular disease. Mitochondria are a major source of placental oxidative stress and may provide a therapeutic target to mitigate the detrimental effects of placental oxidative stress on pregnancy outcomes. A nanoparticle-mediated delivery of a mitochondrial antioxidant to the placenta is a potential novel approach that may avoid unwanted off-target effects on the developing offspring.

Intrauterine growth restriction, a common consequence of prenatal hypoxia, is a leading cause of fetal morbidity and mortality with a significant impact on population health. Hypoxia may increase placental oxidative stress and lead to an abnormal release of placental-derived factors, which are emerging as potential contributors to developmental programming. Nanoparticle-linked drugs are emerging as a novel method to deliver therapeutics targeted to the placenta and avoid risking direct exposure to the fetus. We hypothesize that placental treatment with antioxidant MitoQ loaded onto nanoparticles (nMitoQ) will prevent the development of cardiovascular disease in offspring exposed to prenatal hypoxia. Pregnant rats were intravenously injected with saline or nMitoQ (125 μM) on gestational day (GD) 15 and exposed to either normoxia (21% O2) or hypoxia (11% O2) from GD15-21 (term: 22 days). In one set of animals, rats were euthanized on GD 21 to assess fetal body weight, placental weight and placental oxidative stress. In another set of animals, dams were allowed to give birth under normal atmospheric conditions (term: GD 22) and male and female offspring were assessed at 7 and 13 months of age for in vivo cardiac function (echocardiography) and vascular function (wire myography, mesenteric artery). Hypoxia increased oxidative stress in placentas of male and female fetuses, which was prevented by nMitoQ. 7-month-old male and female offspring exposed to prenatal hypoxia demonstrated cardiac diastolic dysfunction, of which nMitoQ improved only in 7-month-old female offspring. Vascular sensitivity to methacholine was reduced in 13-month-old female offspring exposed to prenatal hypoxia, while nMitoQ treatment improved vasorelaxation in both control and hypoxia exposed female offspring. Male 13-month-old offspring exposed to hypoxia showed an age-related decrease in vascular sensitivity to phenylephrine, which was prevented by nMitoQ. In summary, placental-targeted MitoQ treatment in utero has beneficial sex- and age-dependent effects on adult offspring cardiovascular function.

Some neuropsychiatric disease, including schizophrenia, may originate during prenatal development, following periods of gestational hypoxia and placental oxidative stress. Here we investigated if gestational hypoxia promotes damaging secretions from the placenta that affect fetal development and whether a mitochondria-targeted antioxidant MitoQ might prevent this. Gestational hypoxia caused low birth-weight and changes in young adult offspring brain, mimicking those in human neuropsychiatric disease. Exposure of cultured neurons to fetal plasma or to secretions from the placenta or from model trophoblast barriers that had been exposed to altered oxygenation caused similar morphological changes. The secretions and plasma contained altered microRNAs whose targets were linked with changes in gene expression in the fetal brain and with human schizophrenia loci. Molecular and morphological changes in vivo and in vitro were prevented by a single dose of MitoQ bound to nanoparticles, which were shown to localise and prevent oxidative stress in the placenta but not in the fetus. We suggest the possibility of developing preventative treatments that target the placenta and not the fetus to reduce risk of psychiatric disease in later life.

Intrauterine growth restriction (IUGR) is a common pregnancy complication and is a leading cause of fetal morbidity and mortality. Placental hypoxia contributes to adverse fetal consequences, such as IUGR. Exposing pregnant rats to hypoxia can lead to IUGR; however, assessment of maternal vascular function in a rat model of hypoxia, and the mechanisms that may contribute to adverse pregnancy outcomes, has not been extensively studied. We hypothesized that exposing pregnant rats to hypoxia will affect maternal systemic vascular function and increase the uterine artery resistance index (RI), which will be associated with IUGR. To test this hypothesis, pregnant rats were kept in normoxia (21% O2) or hypoxia (11% O2) from gestational day (GD) 6 to 20. Maternal blood pressure, uteroplacental resistance index (RI) (ultrasound biomicroscopy), and vascular function (wire myography) were assessed in uterine and mesenteric arteries. Fetal weight was significantly reduced ( P < 0.001), while maternal blood pressure was increased ( P < 0.05) in rats exposed to hypoxia. Maternal vascular function was also affected after exposure to hypoxia, including impaired endothelium-dependent vasodilation responses to methacholine in isolated uterine arteries (pEC50 normoxia: 6.55 ± 0.23 vs. hypoxia: 5.02 ± 0.35, P < 0.01) and a reduced uterine artery RI in vivo (normoxia: 0.63 ± 0.04 vs. hypoxia: 0.53 ± 0.01, P < 0.05); associated with an increase in umbilical vein RI (normoxia: 0.35 ± 0.02 vs. hypoxia: 0.45 ± 0.04, P < 0.05). These data demonstrate maternal and fetal alterations in vascular function due to prenatal exposure to hypoxia. Further, although there was a compensatory reduction in uterine artery RI in the hypoxia groups, this was not sufficient to prevent IUGR.

Uterine spiral artery remodeling is required for successful human pregnancy; impaired remodeling is associated with pregnancy complications, including late miscarriage, preeclampsia, and fetal growth restriction. The molecular triggers of remodeling are not known, but it is now clear that there are "trophoblast-independent" and "trophoblast-dependent" stages. Uterine natural killer (uNK) cells are abundant in decidualized endometrium in early pregnancy; they surround spiral arteries and secrete a range of angiogenic growth factors. We hypothesized that uNK cells mediate the initial stages of spiral artery remodeling. uNK cells and extravillous trophoblast (EVT) cells were isolated from early pregnancy decidua and placenta. Chorionic plate arteries from full-term placentas and spiral arteries from nonpregnant myometrium were cultured with angiogenic growth factors or conditioned medium (CM) from uNK cells or EVT or uNK cell/EVT cocultures. In both vessel models, uNK cell CM induced disruption of vascular smooth muscle cells (VSMCs) and breakdown of extracellular matrix components. Angiopoietin (Ang)-1, Ang-2, interferon-γ, and VEGF-C also disrupted VSMC integrity with an Ang-2 inhibitor abrogating the effect of uNK cell CM. These results provide compelling evidence that uNK cells contribute to the early stages of spiral artery remodeling; failure of this process could contribute to pregnancy pathology. © FASEB.

عبارة عن شبكة من أصحاب المصلحة من جميع مستويات المجتمع البحثي التي قامت بصياغة بيان للباحث عن الصحة العقلية والرفاهية والذي يدعو إلى تقييم أفضل طريقة لتغذية واستدامة الصحة العقلية للباحثين ورفاهيتهم من خلال الإجراءات والمبادرات على مستوى السياسات والمؤسسات والمجتمعات والأفراد. يدعو هذا البيان جميع أصحاب المصلحة في النظام البحثي إلى المشاركة في تطوير السياسات التي ترصد وتحسن وتحافظ على الرفاهية والصحة العقلية في بيئة البحث ، وتحديد مقاييس أكثر شمولاً للنجاح والجودة ، ودعم التوازن بين العمل والحياة ، والشمولية ، والوظائف البحثية المستدامة الصديقة للأسرة.