iTRAQ-based quantitative proteomic analysis of thoracic aortas from adult rats born to preeclamptic dams.

BACKGROUND: Preeclampsia and gestational hypertension can cause vascular function impairment in offspring. In our previous work, we described the protein expression profiles of umbilical artery tissues from patients with preeclampsia. METHODS: To gain insights into the mechanisms of vascular dysfunction in adult rats born to preeclamptic dams, we analyzed thoracic aorta tissues by using iTRAQ isobaric tags and 2D nano LC-MS/MS. RESULTS: By using the iTRAQ method, we analyzed 1825 proteins, of which 106 showed significantly different expression in the thoracic aortic. Ingenuity pathway analysis (IPA) showed that the majority of differentially expressed proteins (DEPs) were associated with cardiovascular function. Further analysis indicated that glucose-6-phosphate dehydrogenase (G6PD), which is inhibited by miR-423-5p and activated by TP53, had the strongest effect on cardiovascular function. The expression of G6PD was upregulated in thoracic aorta tissues, as confirmed by Western blotting. The expression of two other vascular function-related proteins, cysteine- and glycine-rich protein 2 (CSRP2) and tubulin alpha-4 A (TUBA4A), was upregulated, as demonstrated by mass spectrometry (MS). CONCLUSIONS: Although the results require further functional validation, these data provide novel findings related to vascular function impairment in the adult offspring of preeclamptic mothers.

Bile acid levels and risk of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy: A meta-analysis.

AIM: We aimed to determine the association between maternal total bile acid (TBA) levels and the risks of adverse perinatal outcomes in pregnant women with intrahepatic cholestasis of pregnancy (ICP) based on a meta-analysis study. METHODS: We searched PubMed for articles published from 2000 to 2015 with a focus on ICP and restriction to the English language. The main perinatal outcomes were preterm birth (PTB), meconium-stained amniotic fluid (MSAF), asphyxia, or respiratory distress syndrome (RDS). Relative risk (RR) with 95% confidence intervals (CI) was the summary statistic. We used a random- or fixed-effects model to calculate the pooled RR according to the heterogeneity test. Subgroup analyses were performed by region and study design. RESULTS: Nine eligible related citations fulfilled the inclusion criteria and were included in this study. Compared with pregnant women with a serum TBA < 40 µmol/L, severe ICP (TBA ≥ 40 µmol/L) was associated with a significantly increased risk of adverse fetal outcomes (pooled RR, 1.96; 95%CI, 1.63-2.35), PTB (pooled RR, 2.23; 95%CI, 1.51-3.29), MSAF (pooled RR, 2.27; 95%CI, 1.81-2.85), and asphyxia or RDS (pooled RR, 1.67; 95%CI, 1.18-2.36). Sensitivity analysis suggested that the study design difference may be a major source of heterogeneity. No publication bias was demonstrated by Begg's test (P > 0.05). CONCLUSION: This meta-analysis indicates that maternal elevated bile acid levels are significantly associated with increased risks of overall adverse perinatal outcomes, PTB, MSAF, and asphyxia or RDS. Serum TBA levels seem to be a useful predictor for the risk of adverse perinatal outcomes.

Association of prenatal obesity and cord blood cytokine levels with allergic diseases in children: A 10-year follow-up cohort study.

Background and aim: Although studies have associated elevated prenatal obesity with increased risk of various diseases in offspring, little is known regarding the immune system. The aim of this study was to evaluate the relationship between prenatal obesity and levels of cytokines in umbilical cord blood and development of allergic disease during the first 10 years of life in an offspring. Methods: A cohort of term infants born at the ShaoXing Women and Children Hospitals in China in 2011 was enrolled in this study. Flow cytometry was performed to measure levels of various cord blood cytokines, namely IL1ß, IL2, IL10, IL6, IL8, IL17, IL12, TNF-α and IFN-γ. Next, logistic regression was used to explore the association of prenatal BMI with the development of allergic disease. The relationship between levels of each cord blood cytokine with prenatal BMI, and allergic disease development was tested using linear and logistic regression analyses, respectively. Results: After 10 years of follow-up, higher prenatal BMI was significantly associated with development of allergic disease in children (HR = 2.45, 95% CI:1.08-5.57, P = 0.033). We also adjusted for maternal age, education and infant gender, and found that prenatal BMI was significantly associated with higher levels of IL12 (P = 0.023) and IL1ß (P = 0.049) in cord blood. Moreover, we adjusted for maternal age, education, allergic dermatitis, gestation age and infant gender, and found that increase in each unit (1.26 pg/ml) in IL17 was associated with a 55.5% higher risk of allergic disease in 10-year-old children (HR = 1.55, 95%Cl: 0.99-2.45, P = 0.056). Meanwhile, after adjusting for maternal age, education level, gestation age, prenatal BMI, gestational weight gain, infant gender and birthweight, we found that for every unit increase in IL10, IL6 and IL1ß, the risk of overweight/obesity in children after 10-year follow-up increased by 18.7% (HR = 1.19, 95%Cl: 1.01-1.40, P = 0.042), 13.9% (HR = 1.14, 95%Cl: 1.02-1.27, P = 0.021) and 41.3% (HR = 1.41, 95%Cl: 1.02-1.95, P = 0.036), respectively. Conclusions: Prenatal obesity was positively correlated with allergic diseases in offspring. Cord blood cytokine may play mediating roles in the associations of prenatal obesity with offspring allergic diseases.

Maternal sodium acetate supplementation promotes lactation performance of sows and their offspring growth performance.

Milk yield and composition are critical determining factors for the early growth and development of neonates. The objective of this experiment was to comprehensively evaluate the effects of dietary sodium acetate (SA) supplementation on the milk yield and composition of sows and the growth performance of their offspring. A total of 80 sows (Landrace × Yorkshire, 3 to 6 parity) were randomly assigned to 2 groups (with or without 0.1% SA) from d 85 of gestation to d 21 of lactation. The result shows that maternal 0.1% SA supplementation significantly increased sows milk yield, milk fat, immunoglobulin A (IgA) and IgG content in milk (P < 0.05), with the up-regulation of short-chain fatty acids receptors (GPR41 and GPR43) expression and the activation of mammalian target of rapamycin complex C1 (mTORC1) signaling pathway. Consistently, in our in vitro experiment, SA also activated mTORC1 signaling in porcine mammary epithelial cells (P < 0.05). Furthermore, the improvement of milk quality and quantity caused by maternal SA supplementation led to the increase in body weight (BW) and average daily weight gain (ADG) of weaning piglets, with the improvement of gut health and colonization of the beneficial bacteria (P < 0.05). In conclusion, maternal supplementation of 0.1% SA improved the lactation performance (milk yield and milk fat) of sows, possibly with the activation of GPR41/GPR43-mTORC1 signaling. Furthermore, enhanced milk quality improved growth performance, gut health and the colonization of beneficial microbial flora of their piglets.

Fetal Congenital Heart Disease Caused by Compound Heterozygous Mutations in the DNAH9 Gene: A Case Report.

Background: Fetal congenital heart disease (CHD) is the most common congenital defect, with an incidence of 0.6-0.8%, accounting for 30-50% of infant congenital disease deaths. The pathogenesis of CHD is still unclear, so an active and effective prenatal diagnosis is very important for the prevention and control of CHD. Herein, a Chinese CHD patient with rare compound heterozygous mutations in the DNAH9 gene was reported, and the 3D structure and functional changes of DNAH9 protein were predicted. Case presentation: A 23-year-old pregnant woman came to our hospital for prenatal diagnosis at 27 weeks of gestation. Both she and her partner were unaffected. Fetal CHD was detected by ultrasound screening. Copy number variation sequencing (CNV-seq) revealed an 81 kb deletion at chr17p12 (11,486,795-11,568,385), including exons 1-15 of DNAH9 gene, which plays a key role in cardiac development. Then, whole exome sequencing (WES) was used and identified a nonsense mutation (c.10975C>T) in DNAH9, which resulted in the mutation of amino acid 3,659 from glutamine to termination. The 3D mutant protein structures were predicted using SWISS-MODEL and showed structural changes from functional ß-sheet and α-helix to termination, respectively. Conclusion: We describe a case of fetal CHD caused by DNAH9 mutations and provide an effective diagnostic technique for identifying intragenic deletions. This diagnostic process can be implicated in prenatal diagnosis of CHD.