Journal of Developmental Origins of Health and Disease最新文献

Exposure to maternal hyperglycemia in utero has been associated with adverse metabolic outcomes in offspring. However, few studies have investigated the relationship between maternal hyperglycemia and offspring cortisol levels. We assessed associations of gestational diabetes mellitus (GDM) with cortisol biomarkers in two longitudinal prebirth cohorts: Project Viva included 928 mother-child pairs and Gen3G included 313 mother-child pairs. In Project Viva, GDM was diagnosed in N = 48 (5.2%) women using a two-step procedure (50 g glucose challenge test, if abnormal followed by 100 g oral glucose tolerance test [OGTT]), and in N = 29 (9.3%) women participating in Gen3G using one-step 75 g OGTT. In Project Viva, we measured cord blood glucocorticoids and child hair cortisol levels during mid-childhood (mean (SD) age: 7.8 (0.8) years) and early adolescence (mean (SD) age: 13.2 (0.9) years). In Gen3G, we measured hair cortisol at 5.4 (0.3) years. We used multivariable linear regression to examine associations of GDM with offspring cortisol, adjusting for child age and sex, maternal prepregnancy body mass index, education, and socioeconomic status. We additionally adjusted for child race/ethnicity in the cord blood analyses. In both Project Viva and Gen3G, we observed null associations of GDM and maternal glucose markers in pregnancy with cortisol biomarkers in cord blood at birth (β = 16.6 nmol/L, 95% CI -60.7, 94.0 in Project Viva) and in hair samples during childhood (β = -0.56 pg/mg, 95% CI -1.16, 0.04 in Project Viva; β = 0.09 pg/mg, 95% CI -0.38, 0.57 in Gen3G). Our findings do not support the hypothesis that maternal hyperglycemia is related to hypothalamic-pituitary-adrenal axis activity.

In this study, we empirically analyse whether in utero exposure to the Ramadan fasting period is negatively associated with child nutrition. The data for the analyses come from a retrospective assessment of 759,799 children from 103 Demographic and Health Surveys (DHS) across 56 countries during 2003-2020. Considering the month-long Ramadan exposure as a natural experiment, we implement an intent-to-treat framework, comparing stunting and underweight among children aged 0-5 years who were exposed to Ramadan fasting at any time in utero with those who were not exposed. Our findings do not show significant evidence to conclude that in utero exposure to the Ramadan fasting period is negatively associated with child nutrition. On the contrary, except for stunting in Muslim children who had in utero exposure to Ramadan fasting during the first months of pregnancy, we find no significant association between in utero exposure to Ramadan fasting and child stunting and underweight. Our main results are robust to multiple robustness checks.

Maternal prenatal psychological distress, which includes depression and anxiety, affects the onset of autism spectrum disorder (ASD). However, there is no consistent knowledge regarding at which term during pregnancy psychological distress affects the risk of ASD among children. We used a dataset obtained from the Japan Environment and Children's Study, which is a nationwide prospective birth cohort study, to evaluate the association between the six-item Kessler Psychological Distress Scale (K6) and ASD among 3-year-old children. A total of 78,745 children were analyzed, and 355 of them were diagnosed with ASD (0.45%). The maternal K6 was administered twice during pregnancy: at a median of 15.1 weeks (M-T1) and at that of 27.4 weeks (M-T2) of gestation. Multivariate logistic regression analyses demonstrated that the group with a maternal K6 score of ≥5 at both M-T1 and M-T2 was significantly associated with ASD among the children (adjusted odds ratio, 1.440; 95% confidence interval, 1.104-1.877) compared to the group with a score of ≤4 at both M-T1 and M-T2. There was no significant difference between the group with a score of ≥5 only at M-T1 or M-T2 and that with a score of ≤4 at both M-T1 and M-T2. In conclusion, from the first to the second half of pregnancy, continuous maternal psychological distress was associated with ASD among 3-year-old children. Contrarily, in the group without persistent maternal psychological distress during pregnancy, there was no significant association.

Exposure to pregnancy complications, including preeclampsia (PE), has lifelong influences on offspring's health. We have previously reported that experimental PE, induced in mice by administration of adenoviral sFlt1 at gestational day 8.5 combined with LPS at day 10.5, results in symmetrical growth restriction in female and asymmetrical growth restriction in male offspring. Here, we characterize the molecular phenotype of the fetal brain and liver with respect to gene transcription and DNA methylation at the end of gestation.In fetal brain and liver, expression and DNA methylation of several key regulatory genes is altered by PE exposure, mostly independent of fetal sex. These alterations point toward a decreased gluconeogenesis in the liver and stimulated neurogenesis in the brain, potentially affecting long-term brain and liver function. The observed sex-specific growth restriction pattern is not reflected in the molecular data, showing that PE, rather than tissue growth, drives the molecular phenotype of PE-exposed offspring.

Fetal and child development are shaped by early life exposures, including maternal health states, nutrition and educational and home environments. We aimed to determine if suboptimal pre-pregnancy maternal body mass index (BMI; underweight, overweight, obese) would associate with poorer cognitive outcomes in children, and whether early life nutritional, educational and home environments modify these relationships. Self-reported data were obtained from mother-infant dyads from the pan-Canadian prospective Maternal-Infant Research on Environmental Chemicals cohort. Relationships between potential risk factors (pre-pregnancy maternal BMI, breastfeeding practices and Home Observation Measurement of the Environment [HOME] score) and child cognitive development at age three (Weschler's Preschool and Primary Scale of Intelligence, Third Edition scale and its subcategories) were each evaluated using analysis of variance, multivariable regression models and moderating analyses. Amongst the 528 mother-child dyads, increasing maternal pre-pregnancy BMI was negatively associated with scores for child full-scale IQ (β [95% CI]; -2.01 [-3.43, -0.59], p = 0.006), verbal composite (-1.93 [-3.33, -0.53], p = 0.007), and information scale (-0.41 [-0.70, -0.14], p = 0.003) scores. Higher maternal education level or HOME score attenuated the negative association between maternal pre-pregnancy BMI and child cognitive outcome by 30%-41% and 7%-22%, respectively, and accounted for approximately 5%-10% greater variation in male children's cognitive scores compared to females. Maternal education and higher quality home environment buffer the negative effect of elevated maternal pre-pregnancy BMI on child cognitive outcomes. Findings suggest that relationships between maternal, social and environmental factors must be considered to reveal pathways that shape risk for, and resiliency against, suboptimal cognitive outcomes in early life.

Zinc is an important nutrient involved in cell division, physical growth, and immune system function. Most studies evaluating the nutritional status related to zinc and prematurity were conducted with hospitalized preterm infants. These studies show controversial results regarding the prevalence of deficiency, clinical implications, and the effect of zinc supplementation on mortality, infectious diseases, and growth in these groups. This study aimed to compare serum and erythrocyte zinc levels in a group of preterm and full-term infants after 9 months of age, and related the zinc levels to dietary intake and anthropometric indicators in both groups. This cross-sectional study compared 43 preterm infants (24 to 33 weeks) aged 9-24 months to 47 full-term healthy infants. Outcome measures: anthropometric indicators and dietary intake. Blood sample for serum and erythrocyte zinc levels (ICP-MS, Inductively Coupled Plasma Mass Spectrometry). There was no difference between the groups regarding the mean of serum and erythrocyte zinc. Variables associated with higher serum zinc levels were breastfeeding at evaluation (β = 20.11 µg/dL, 95% CI 9.62-30.60, p < 0.001) and the later introduction of solid foods (β = 6.6 µg/dL, 95% CI 5.3-11.4, p < 0.001). Breastfeeding was also associated with higher erythrocyte zinc levels. The zinc levels were adequate in both groups, there was no association with anthropometric indicators or dietary intake and were slightly influenced by breastfeeding and time of solid food introduction.

In the United States, cardiovascular disease is the leading cause of death and the rate of maternal mortality remains among the highest of any industrialized nation. Maternal cardiometabolic health throughout gestation and postpartum is representative of placental health and physiology. Both proper placental functionality and placental microRNA expression are essential to successful pregnancy outcomes, and both are highly sensitive to genetic and environmental sources of variation. Placental pathologies, such as preeclampsia, are associated with maternal cardiovascular health but may also contribute to the developmental programming of chronic disease in offspring. However, the role of more subtle alterations to placental function and microRNA expression in this developmental programming remains poorly understood. We performed small RNA sequencing to investigate microRNA in placentae from the Rhode Island Child Health Study (n = 230). MicroRNA counts were modeled on maternal family history of cardiovascular disease using negative binomial generalized linear models. MicroRNAs were considered to be differentially expressed at a false discovery rate (FDR) less than 0.10. Parallel mRNA sequencing data and bioinformatic target prediction software were then used to identify potential mRNA targets of differentially expressed microRNAs. Nine differentially expressed microRNAs were identified (FDR < 0.1). Bioinformatic target prediction revealed 66 potential mRNA targets of these microRNAs, many of which are implicated in TGFβ signaling pathway but also in pathways involving cellular metabolism and immunomodulation. A robust association exists between familial cardiovascular disease and placental microRNA expression which may be implicated in both placental insufficiencies and the developmental programming of chronic disease.

The functional differentiation of the mammary gland (MG) is fundamental for the prevention of mammary pathologies. This process occurs throughout pregnancy and lactation, making these stages key events for the study of pathologies associated with development and differentiation. Many studies have investigated the link between mammary pathologies and thyroid diseases, but most have ignored the role of thyroid hormone (TH) in the functional differentiation of the MG. In this work, we show the long-term impact of hypothyroidism in an animal model whose lactogenic differentiation occurred at low TH levels. We evaluated the ability of the MG to respond to hormonal control and regulate cell cycle progression. We found that a deficit in TH throughout pregnancy and lactation induces a long-term decrease in Rb phosphorylation, increases p53, p21, Cyclin D1 and Ki67 expression, reduces progesterone receptor expression, and induces nonmalignant lesions in mammary tissue. This paper shows the importance of TH level control during mammary differentiation and its long-term impact on mammary function.

Prenatal glucocorticoid overexposure causes adult metabolic dysfunction in several species but its effects on adult mitochondrial function remain largely unknown. Using respirometry, this study examined mitochondrial substrate metabolism of fetal and adult ovine biceps femoris (BF) and semitendinosus (ST) muscles after cortisol infusion before birth. Physiological increases in fetal cortisol concentrations pre-term induced muscle- and substrate-specific changes in mitochondrial oxidative phosphorylation capacity in adulthood. These changes were accompanied by muscle-specific alterations in protein content, fibre composition and abundance of the mitochondrial electron transfer system (ETS) complexes. In adult ST, respiration using palmitoyl-carnitine and malate was increased after fetal cortisol treatment but not with other substrate combinations. There were also significant increases in protein content and reductions in the abundance of all four ETS complexes, but not ATP synthase, in the ST of adults receiving cortisol prenatally. In adult BF, intrauterine cortisol treatment had no effect on protein content, respiratory rates, ETS complex abundances or ATP synthase. Activity of citrate synthase, a marker of mitochondrial content, was unaffected by intrauterine treatment in both adult muscles. In the ST but not BF, respiratory rates using all substrate combinations were significantly lower in the adults than fetuses, predominantly in the saline-infused controls. The ontogenic and cortisol-induced changes in mitochondrial function were, therefore, more pronounced in the ST than BF muscle. Collectively, the results show that fetal cortisol overexposure programmes mitochondrial substrate metabolism in specific adult muscles with potential consequences for adult metabolism and energetics.

The sequential occurrence of three layers of smooth muscle layers (SML) in human embryos and fetus is not known. Here, we investigated the process of gut SML development in human embryos and fetuses and compared the morphology of SML in fetuses and neonates. The H&E, Masson trichrome staining, and Immunohistochemistry were conducted on 6-12 gestation week human embryos and fetuses and on normal neonatal intestine. We showed that no lumen was seen in 6-7^th gestation week embryonic gut, neither gut wall nor SML was developed in this period. In 8-9^th gestation week embryonic and fetal gut, primitive inner circular SML (IC-SML) was identified in a narrow and discontinuous gut lumen with some vacuoles. In 10^th gestation week fetal gut, the outer longitudinal SML (OL-SML) in gut wall was clearly identifiable, both the inner and outer SML expressed α-SMA. In 11-12^th gestation week fetal gut, in addition to the IC-SML and OL-SML, the muscularis mucosae started to develop as revealed by α-SMA immune-reactivity beneath the developing mucosal epithelial layer. Comparing with the gut of fetuses of 11-12^th week of gestation, the muscularis mucosae, IC-SML, and OL-SML of neonatal intestine displayed different morphology, including branching into glands of lamina propria in mucosa and increased thickness. In conclusions, in the human developing gut between week-8 to week-12 of gestation, the IC-SML develops and forms at week-8, followed by the formation of OL-SML at week-10, and the muscularis mucosae develops and forms last at week-12.