SERPINA5 may promote the development of preeclampsia by disruption of the uPA/uPAR pathway.

Preeclampsia (PE) is the leading cause of maternal and fetal morbidity or mortality but lacks reliable methods for early diagnosis. In a previous study, serum SERPINA5 levels were higher in women with PE before the clinical manifestation of the disease. This study aimed to evaluate the efficacy of SERPINA5 in predicting PE and investigate its role in trophoblast cell biology. A multicenter, 2-stage observational case-control study was performed to develop and validate an early predictive PE model based on SERPINA5, maternal characteristics, and inflammatory factors. To further understand the relationship between SERPINA5 and PE, SERPINA5 was overexpressed or knocked down in extravillous trophoblast cells (EVT) and a pregnant rat model. After development and initial validation, a model that combined SERPINA5 and inflammatory factors had a high predictive ability for PE before 20 weeks gestation with an AUC of 0.90 (95% CI 0.83-0.96). It also demonstrated that SERPINA5 inhibited primary EVT cell invasion by disrupting the urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor (uPA/uPAR) pathway, in turn, is involved in the development of PE. In vivo experiments also proved that overexpression of SERPINA5 induced a PE-like syndrome (hypertension and proteinuria) in pregnant rats. Therefore, serum SERPINA5 is a promising early biomarker of PE, suggesting that it may be involved in placental development through its action on the uPA/uPAR system prior to the clinical manifestation of PE.

Mediating effects of gut microbiota in the associations of air pollutants exposure with adverse pregnancy outcomes.

BACKGROUND: The aim of this study was to investigate alterations in gut microbiota after exposure to air pollutants during pregnancy and its mediation effect in inducing adverse pregnancy outcomes (APOs). METHODS: Participants (n = 916) were enrolled between 2017 and 2018 from a prospective cohort study of pregnant women in Guangzhou, China. The relative abundance of fecal microbiota was profiled using 16SrRNA V4 region sequencing. Exposure to air pollutants in each trimester of pregnancy was assessed using measurements from the nearest monitoring station. APOs including pre-term birth (PTB), post-term birth (POTB), low birth weight (LBW), macrosomia fetus (MF), birth defects (BDs), pathological cesarean section (PCS) and postpartum hemorrhage (PPH)) were determined by referring to reliable clinical records and diagnostic criteria. Univariate analysis, multivariate analysis and mediation analysis were performed to estimate the association among air pollutants, gut microbiota and APOs. RESULTS: Air pollutants exposure during pregnancy was significantly correlated with the alterations in the gut microbiota, and increased risks of various APOs by 1.07-1.36-fold (P < 0.05). The mediation analyses indicated that alterations in Eggerthella, Phascolarctobacterium and Clostridium partially mediated the effects of air pollutants exposure (PM2.5, PM10, O3, NO2 and SO2) on APOs. The relative abundance of f_Micrococcaceae explained 11.39%, 64.90% and 54.80% of the correlation between SO2, PM2.5, PM10 and POTB, respectively; whereas g_Rothia explained 11.97%, 67.80% and 54.50%, respectively. g_Parabacteroides explained 53.0% of the correlation between PM2.5 and PTB. CONCLUSIONS: Increased air pollutants exposure during pregnancy may induce adverse pregnancy outcomes via alteration of the gut microbiota.

The potential risk factors of placenta increta and the role of octamethylcyclotetrasiloxane.

BACKGROUND: The study aimed to investigate the potential risk factors for the placenta accreta spectrum (PAS), determine the predictive value of a diagnostic model, and evaluate the effects of octamethylcyclotetrasiloxane (OMCTS) on trophoblast proliferation and migration. METHODS: This case-control study included 244 pregnant women with PAS and 327 normal pregnant women who visited Guangzhou Women and Children's Medical Centre, China, from January 2014 to December 2017. Blood was collected from 42 women with PAS and 77 controls, and plasma specimens were analyzed by gas chromatography-time-of-flight mass spectrometry. In addition, the proliferation and migration of trophoblast cells were examined after treatment with OMCTS. RESULTS: We found an association between the risk of PAS and clinical factors related to fasting blood glucose levels (BS0, OR = 5.78), as well as factors related to endometrial injury [history of cesarean section (OR = 179.59), uterine scarring (OR = 68.37), and history of abortion (OR = 5.66)]. Equally important, pregnant women with PAS had significantly higher plasma OMCTS concentrations than controls. In vitro, we found that OMCTS could promote the proliferation and migration of HTR8/SVneo cells. The model of combining clinical factors and OMCTS had a good performance in PAS prediction (AUC = 0.97, 95% CI 0.78-0.93). CONCLUSIONS: The early diagnosis of PAS in pregnant women requires assessing risk factors, metabolic status, and BS0 levels before 20 weeks of gestation. OMCTS may be related to the development of PAS by promoting trophoblast cell proliferation and migration.

Association of self-rated health with chronic disease, mental health symptom and social relationship in older people.

Chronic disease, mental health symptoms and poor social relations are reported common causes for poor self-rated health in older people. To assess the co-occurrence rate of chronic diseases, poor mental health and poor social relationships in older people, and determine their association with self-rated health. 6,551 older people in Zhongshan, China, participated a large health surveillance program were randomly selected and questioned about their SRH, chronic conditions, mental health symptoms and social relationships. The association between self-rated health and chronic conditions, poor mental health, social relationships, and their co-occurrence were analyzed. 56.4% of participants reported poor self-rated health. 39.1% experienced at least one chronic disease. 29.0% experienced one or more mental health symptoms; 19.5% experienced at least one poor social relationship. 7.8% had co-occurrence of chronic diseases, mental health problems, and poor social relationships. Logistic regressions showed that poor self-rated health was associated with chronic diseases, poor mental health, poor social relationships and their co-occurrence. The findings indicate the importance of managing chronic disease, poor mental health and poor social relationships for older people.

Serum complement proteomics reveal biomarkers for hypertension disorder of pregnancy and the potential role of Clusterin.

INTRODUCTION: Hypertension disorder of pregnancy (HDP) is one of the leading causes of maternal and foetal illness. The aim of the current study was to identify and verify novel serum markers for HDP. METHODS: A label-free LC-MS/MS method was used to establish the serum proteomic profiles of 12 pre-HDP (before clinical diagnosis of HDP) pregnancies and verify prioritized candidates in the verification set of 48 pre-HDP pregnancies. These biomarkers were revalidated by ELISA in an independent cohort of 88 pre-HDP pregnancies. Subsequently, the candidate biomarkers were histologically analysed by immunohistochemistry, and function was evaluated in TEV-1 cells. RESULTS: We identified 33 proteins with significantly increased abundance and 14 with decreased abundance (peptide FDR ≤ 1%, P < 0.05). Complement was one of the top enriched components in the pre-HDP group compared with the control group. Three complement factors (CLU, CFHR5, and CRP) were significantly increased in the three sets, of which CLU was a critical factor for the development of HDP (OR = 1.22, P < 0.001). When these three factors and body weight were combined, the AUC was 0.74, with a sensitivity of 0.67 and specificity of 0.68 for HDP prediction compared with normal pregnancy. In addition, inflammation-induced CLU could inhibit the invasion of TEV-1 cells. CONCLUSIONS: Complement proteins may play an essential role in the occurrence of HDP by acting on trophoblast cells. CLU may be a high-risk factor for HDP, and the models combining candidates show reasonable screening efficiency of HDP in the first half of pregnancy.

Circulating expression of Hsa_circRNA_102893 contributes to early gestational diabetes mellitus detection.

Due to a poor availability of reliable biomarkers, detecting gestational diabetes mellitus (GDM) in early pregnancy remains a challenge. Novel biomarkers like Circular RNAs (circRNAs) may be a promising diagnostic tool. The aim of this study was (a) to identify circRNAs deregulated in GDM and (b) evaluate the potential of circRNAs in detecting GDM. The circRNAs expression profiling in 6 paired women (with and without GDM) was measured by microarray. The levels of five most relevant circRNAs were validated in 12 paired participants by qRT-PCR. To verify the reproducibility of qRT-PCR, significantly differential expressed circRNA levels were confirmed in 18 paired participants. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value. The areas under ROC curves of hsa_circRNA_102893 were 0.806 (95% CI 0.594-0.937) and 0.741 (0.568-0.872) in training set and test set, respectively. Circulating circRNAs reflect the presence of GDM. Hsa_circRNA_102893 may be a potential novel and stable noninvasive biomarker for detecting GDM in early pregnancy.

Systematic analysis of gut microbiota in pregnant women and its correlations with individual heterogeneity.

The woman's gut microbiota during pregnancy may support nutrient acquisition, is associated with diseases, and has been linked to infant health. However, there is limited information on gut microbial characteristics and dependence in pregnant women. In this study, we provide a comprehensive overview of the gut microbial characteristics of 1479 pregnant women using 16S rRNA gene sequencing of fecal samples. We identify a core microbiota of pregnant women, which displays a similar overall structure to that of age-matched nonpregnant women. Our data show that the gestational age-associated variation in the gut microbiota, from the ninth week of gestation to antepartum, is relatively limited. Building upon rich metadata, we reveal a set of exogenous and intrinsic host factors that are highly correlated with the variation in gut microbial community composition and function. These microbiota covariates are concentrated in basic host properties (e.g., age and residency status) and blood clinical parameters, suggesting that individual heterogeneity is the major force shaping the gut microbiome during pregnancy. Moreover, we identify microbial and functional markers that are associated with age, pre-pregnancy body mass index, residency status, and pre-pregnancy and gestational diseases. The gut microbiota during pregnancy is also different between women with high or low gestational weight gain. Our study demonstrates the structure, gestational age-associated variation, and associations with host factors of the gut microbiota during pregnancy and strengthens the understanding of microbe-host interactions. The results from this study offer new materials and prospects for gut microbiome research in clinical and diagnostic fields.