Objective: The aim of this study was to investigate the effects of prenatal heavy metal (arsenic, cadmium, manganese) exposure on infant neurodevelopment through a systematic review and meta-analysis, elucidating the toxicological mechanisms and dose–response relationships for consideration in environmental risk assessment. Methods: Following the PRISMA guidelines, systematic searches were conducted in PubMed, Embase, and other databases, ultimately resulting in 17 observational studies involving 6907 participants. Results: Arsenic (As): A 50% increase in arsenic exposure was associated with a reduction of 0.51 points in the Mental Development Index (MDI; 95% CI: −1.43 to 0.4) and 0.15 points in the Psychomotor Development Index (PDI; 95% CI: −0.96 to 0.65). However, these results did not achieve statistical significance (p > 0.05). Cadmium (Cd): Prenatal cadmium exposure significantly decreased the Full-Scale Intelligence Quotient (FSIQ) in children aged 5–9 years. A 50% increase in cadmium exposure resulted in a 0.44-point drop in the FSIQ (95% CI: −0.67 to −0.21, p < 0.05), with stable effects (I² = 0%). Manganese (Mn): Manganese exposure showed a negative association with the MDI (β = −0.11) and PDI (β = −0.18). However, a high degree of heterogeneity was observed (I² = 20.89–73.35%), and some studies suggested potential risks even at low exposure levels. Sensitivity analyses indicated that the heterogeneity in the arsenic and manganese results mainly stemmed from individual study differences (e.g., sample characteristics), whereas the cadmium effects were consistent. Conclusions: Prenatal heavy metal exposure (notably cadmium) adversely impacts neurodevelopment, even at low doses. Future research should prioritize critical exposure windows, mixed effects, and sex-specific vulnerabilities. Strengthening environmental monitoring and prenatal guidelines is crucial to mitigate developmental risks.

Introduction: Gestational diabetes mellitus (GDM) refers to hyperglycemia first recognized during pregnancy, characterized by decreased insulin sensitivity and impaired glucose metabolism. Dynamic fusion and fission processes within mitochondria play critical roles in maintaining glucose metabolism homeostasis. Given the fundamental role of mitochondrial fission factor (MFF) in mitochondrial fission, the intention of this study was to investigate mitochondrial dynamics in the placentae of GDM patients and explore the role of MFF in the etiopathogenesis and progression of GDM through the modulation of glucose metabolism and insulin resistance. Methods: 40 Placental tissues were obtained from pregnant women undergoing cesarean section with GDM (n=20) and those with normoglycemia (n=20). To mimic the intrauterine high glucose environment, immortalized human-derived first-trimester extravillous trophoblast cells HTR8/SVneo were used and treated in a high glucose environment. Immunofluorescence was utilized to analyze MFF expression in placental tissues and mitochondrial length in HTR8/SVneo cells. The expression levels of glucose transporters (GLUTs) and other pivotal proteins involved in mitochondrial dynamics and the insulin signaling pathway, were assessed by Western blotting. Additionally, cellular glucose uptake capacity was determined using a glucose assay kit. Results: MFF expression was greater in the GDM group than in the normoglycemic group. In a high-glucose environment, the expression of fusion-related proteins OPA1, MFN1 and MFN2 decreased while the expression of DRP1 and MFF increased, indicating that the mitochondrial dynamics of trophoblast cells shift toward fission. Elevated mitochondrial fission hinders the insulin signaling pathway, resulting in a reduction in glucose uptake by HTR8/SVneo cells and a concurrent decrease in GLUT4 expression. Discussion: Our study demonstrates that MFF-mediated mitochondrial fission inhibits insulin sensitivity and upregulates glucose transport in GDM, which is related to offspring exposure to a hyperglycemic intrauterine environment. These results provide a novel therapeutic target for addressing GDM that may mitigate unfavorable pregnancy outcomes.

Background and Objectives: The escalating prevalence of gestational diabetes mellitus (GDM) and the limitations associated with utilizing body mass index (BMI) as a predictive measure underscore the imperative need for identifying an optimal early pregnancy predictor. Such a predictor not only mitigates the risk of GDM but also allows for timely implementation of interventions. Materials and Methods: This meta-analysis aimed to explore the association between visceral adipose tissue (VAT) depth and the risk of GDM. A thorough search of PubMed, Embase, and Web of Science databases was conducted up to 30 September 2023. The analysis employed a random-effects model to assess the relationship between VAT depth and the likelihood of GDM. Results: The inclusion criteria encompassed seven studies involving 1315 women, including 225 diagnosed with GDM. Significantly lower VAT depth was observed in the non-GDM group in comparison to the GDM group (Standardized Mean Difference [SMD]: 0.84; 95% Confidence Interval [CI]: 0.52–1.15; p < 0.001). Substantial statistical heterogeneity was noted among studies (I² = 72.88%, p = 0.001). Through meticulous sensitivity and subgroup analyses, the source of heterogeneity was identified and thoroughly discussed. Subgroup analyses suggest that different GDM diagnostic criteria and VAT definitions all indicate higher VAT depth in GDM patients during early pregnancy. Conclusions: Our findings propose that, during the first trimester, GDM patients exhibit higher VAT depth compared to non-GDM women, highlighting VAT depth as a potential predictive factor for GDM in early pregnancy. This study contributes valuable evidence to the growing body of knowledge surrounding novel predictors for GDM, emphasizing the importance of early intervention strategies.

Gestational diabetes mellitus (GDM) is a common complication during pregnancy, which can have harmful health consequences for both the mother and the fetus. Given the placenta’s crucial role as an endocrine organ during pregnancy, exploring and validating key genes in the placenta hold significant potential in the realm of GDM prevention and treatment. In this study, differentially expressed genes (DEGs) were identified from two databases, GSE70493 and PRJNA646212, and verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in placenta tissues. DEGs expression was detected in normal or high-glucose-treated HTR8/SVneo cells. We also investigated the relationship between DEGs and glucose levels in GDM patients. By selecting the intersection of the two databases, we screened 20 DEGs, which were validated in GDM patients. We observed an up-regulation of SLAMF, ALDH1A2, and CHI3L2, and a down-regulation of HLA-E, MYH11, HLA-DRB5, ITGAX, GZMB, NAIP, TMEM74B, RANBP3L, PAEP, WT-1, and CEP170. We conducted further investigations into the expression of DEGs in HTR8/SVneo cells exposed to high glucose, revealing a significant upregulation in the expression of SERPINA3, while the expressions of HLA-E, BCL6, NAIP, PAEP, MUC16, WT-1, and CEP170 were decreased. Moreover, some DEGs were confirmed to have a positive or negative correlation with blood glucose levels of GDM patients through correlation analysis. The identified DEGs are anticipated to exert potential implications in the prevention and management of GDM, thereby offering potential benefits for improving pregnancy outcomes and long-term prognosis of fetuses among individuals affected by GDM.

Introduction: Previous studies have shown that pregnant women with systemic lupus erythematosus (SLE) tend to have a higher risk of adverse pregnancy outcomes, but the potential causal role remained unclear. In this study, we aimed to investigate the causal relationship between SLE and some common pregnancy complications and outcomes using two-sample Mendelian randomization (MR). Methods: The genetic tools were derived from genome-wide association studies of SLE and pregnancy complications and outcomes. MR analysis was performed using inverse variance weighting as primary method. Sensitivity analyses were performed to evaluate the robustness of the results. A retrospective analysis was conducted on 200 pregnant women with SLE and a control group of pregnant women delivering at Tongji Hospital. Results: In the results, we found that genetic susceptibility to SLE was associated with a higher risk of gestational diabetes mellitus (OR = 1.028, 95% CI: 1.006– 1.050), premature delivery (OR = 1.039, 95% CI: 1.013– 1.066), polyhydramnios (OR = 1.075, 95% CI: 1.004– 1.151) and premature rupture of membranes (OR = 1.030, 95% CI: 1.001– 1.060). Some of the retrospective analysis results align with the findings from the MR analysis, indicating that pregnant women with SLE have a higher risk of developing gestational diabetes mellitus and preterm birth. Additionally, although MR analysis did not reveal a causal relationship between SLE and preeclampsia/eclampsia, retrospective analysis discovered that SLE pregnant women are more susceptible to developing preeclampsia/eclampsia (OR = 2.935, 95% CI: 1.118– 7.620). Conclusion: Our study findings suggest a potential causal relationship between SLE and increased risks of gestational diabetes and preterm delivery. Clinical data indicate that pregnant women with SLE are more prone to developing preeclampsia/eclampsia. Clinicians need to be vigilant about the occurrence of these conditions when managing pregnant women with SLE.

Background: Early-onset preeclampsia (EOPE) is frequently complicated by fetal growth restriction (FGR). The sFlt-1/PlGF ratio reflects maternal angiogenic imbalance but provides limited insight into placental pathology-the root cause of preeclampsia. Collagen XVIIA1 (COLXVIIA1), a transmembrane hemidesmosomal collagen expressed in trophoblasts, may serve as a biomarker of placental injury. Methods: Circulating COLXVIIA1 was first measured in gestational age–matched peripheral blood samples from EOPE and normotensive pregnancies (n = 6 per group). Placental origin was assessed using paired uterine and peripheral vein samples (n = 9). Placental COLXVIIA1 expression, localisation, and processing were analysed in normotensive and EOPE placentas. Trophoblast-derived extracellular vesicles (TB-sEVs) were isolated from ex vivo perfused placentas to assess COLXVIIA1 packaging. In a prospective cohort of 167 women with suspected preeclampsia, circulating COLXVIIA1 was analysed alongside PlGF and sFlt-1, and diagnostic performance of the COLXVIIA1/PlGF ratio was compared with sFlt-1/PlGF. Findings: Circulating COLXVIIA1 levels were significantly elevated in EOPE compared with gestational age–matched controls, indicating independence from gestational age. Uterine vein levels exceeded peripheral levels, consistent with placental release. COLXVIIA1 expression was localised to trophoblasts and amniotic epithelium. In EOPE placentas, COLXVIIA1-enriched hotspots co-localised with fibrin nodules, perivillous fibrin deposition, and peri-infarct regions. Increased proteolytic processing (∼120 kDa ectodomain) and preferential packaging of transmembrane COLXVIIA1 into TB-sEVs were observed. The COLXVIIA1/PlGF ratio performed comparably to sFlt-1/PlGF for overall preeclampsia and showed strong predictive accuracy for EOPE with FGR (AUC = 0.858), confirmed by bootstrap analysis. Interpretation: Abnormal COLXVIIA1 expression, processing and release reflects trophoblast response to structural injury and provides a circulating signal complementary to angiogenic markers. The COLXVIIA1/PlGF ratio captures a distinct dimension of placental pathology and may improve risk stratification in EOPE, particularly in pregnancies complicated by FGR.