Ling Feng

The ovarian lymphatic vasculature has emerged as a potential regulator of ovarian function, yet its role in follicular development remains poorly defined. Here, we aimed to elucidate the dynamic changes in ovarian lymphatic vessels during follicular development and to determine whether lymphatic vessels contribute to ovarian function by regulating the immune microenvironment. Ovarian lymphatic remodeling was characterized during different follicular stages, throughout the estrous cycle, and following superovulation using immunofluorescence imaging. Lymphangiogenesis was inhibited with the vascular endothelial growth factor receptor 3 (VEGFR3) inhibitor SAR131675 to evaluate the effects on follicular development and macrophage accumulation in mice. Transcriptomic, tissue localization, and migration assays with C-C motif chemokine ligand 21 (CCL21)- or C-C chemokine receptor type 7 (CCR7)- blocking antibodies were used to investigate CCL21-CCR7 signaling in lymphatic endothelial cell (LEC)-mediated macrophage migration. Ovarian lymphatic vessels underwent dynamic remodeling, with lymphatic density peaking during the luteal phase. Macrophages preferentially localized near lymphatic vessels, and their abundance paralleled lymphatic remodeling across reproductive stages. Inhibition of lymphangiogenesis reduced follicular development, ovulation, corpus luteum formation, and macrophage accumulation. Mechanistically, ovarian lymphatic endothelial cells highly expressed CCL21, which promoted macrophage migration through CCR7 signaling. Collectively, these findings identify ovarian lymphatic vessels as previously unrecognized regulators of the ovarian immune microenvironment, with CCL21-CCR7 signaling mediating lymphatic endothelial cell–macrophage communication to support ovarian function.

Objectives: This study aimed to evaluate the efficacy and safety of multispecies probiotics in patients with constipation during pregnancy. Methods: This Phase 2, randomized, double‐blind, placebo‐controlled trial was conducted across 10 hospitals in China. One hundred and twenty‐two pregnant females with constipation were randomly assigned in a 2:1 ratio to receive either multispecies probiotics or placebo for 8 weeks. The primary efficacy endpoint was the proportion of patients who achieved a mean CSBM frequency of ≥ 3 per week across the entire 8‐week treatment period, together with an increase of ≥ 1 CSBM per week from the baseline weekly average. Results: The overall response rate did not differ significantly between probiotics (22.78%) and placebo groups (20.51%) ( p = 0.779). Weekly response rates showed different temporal patterns between groups (P for interaction = 0.024); however, this did not result in a significant between‐group difference at Week 8. In post hoc exploratory subgroup analyses, for patients with baseline SBM < 3/week, baseline straining score ≤ 2, baseline stool consistency score ≤ 2 (Type 1 or 2), and gestational weeks > 20 weeks, the weekly response rate in probiotics increased faster during the treatment period. The probiotic treatment was well tolerated, with no serious adverse events observed. Conclusions: Multispecies probiotics were safe and well tolerated during pregnancy but did not significantly improve the prespecified primary endpoint within an 8‐week treatment period. Post hoc subgroup analyses suggested potentially heterogeneous response trajectories according to baseline bowel frequency, straining severity, stool consistency, and gestational age; however, these findings should be interpreted with caution.

Members of the genus Corynebacterium are widely distributed across human mucosal surfaces and are increasingly recognized as important components of the female reproductive tract microbiota. However, their diversity is underestimated due to limitations of conventional cultivation approaches. In this study, a novel bacterial strain, designated TJG_1^T, was isolated from vaginal swab samples of a pregnant woman with preeclampsia (PE) using droplet-based microfluidic single-cell cultivation. Strain TJG_1^T was characterized as a Gram-positive, non-spore-forming, non-motile short rod. Phylogenetic analysis based on the 16 S rRNA gene sequence placed the strain within the genus Corynebacterium, with the highest sequence similarity to Corynebacterium coyleae (97.39%). Whole-genome sequencing revealed a genome size of 2,481,283 bp with a G + C content of 61.52 mol%. Average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain TJG_1^T and its closest relatives were below the accepted species thresholds, supporting its classification as a novel species. Functional genome annotation identified genes associated with metabolism, transport systems, putative antimicrobial resistance, and predicted host interaction-related traits. In vitro assays showed that neither bacterial metabolites nor live cells significantly affected trophoblast cell viability or oxidative stress-related gene expression under the tested conditions. Although alterations in cell migration behavior were observed following exposure to live bacteria, these changes were not accompanied by significant differences in migration-related gene expression. Strain TJG_1^T represents a novel species within the genus Corynebacterium. This study highlights the utility of droplet-based cultivation for recovering previously underrepresented vaginal bacteria and expands current knowledge of Corynebacterium diversity in the female reproductive tract.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease that contributes substantially to recurrent pregnancy loss, fetal death, intrauterine growth restriction, and preeclampsia, posing major threats to maternal and fetal health. These obstetric complications exhibit clinical similarities to those resulting from vaginal dysbiosis, yet the vaginal microbiota in APS pregnancies has not been systematically investigated. In this study, we characterized the vaginal microbiome in 33 pregnant women with APS and 90 healthy controls using 16S rRNA gene sequencing. We identified a unique microbial signature in APS pregnancies that differed from the commonly observed pattern of increased microbial diversity and Lactobacillus depletion seen in classical vaginal dysbiosis. Specifically, while overall alpha diversity and Lactobacillus dominance were preserved, we observed distinct compositional restructuring characterized by selective depletion of Lactobacillus johnsonii and marked enrichment of Bifidobacterium dentium . A logistic regression model integrating the relative abundances of these microbial biomarkers demonstrated robust diagnostic performance in differentiating pregnancies with APS from healthy pregnancies, with risk scores significantly correlating with clinical parameters and pregnancy outcomes. This study demonstrates that pregnant women with APS display a distinct vaginal microbiome pattern defined by species-specific compositional restructuring rather than global dysbiosis. These microbial alterations may contribute to APS-related pregnancy morbidity, highlighting vaginal microbial signatures as promising noninvasive biomarkers for risk stratification and potential therapeutic targets in obstetric APS management. IMPORTANCE: Antiphospholipid syndrome (APS) is an autoimmune disease that causes recurrent miscarriage, fetal death, and pregnancy complications in women of reproductive age. While coagulation dysfunction is a known contributing factor, whether APS is accompanied by vaginal microbiota alterations and their role in adverse outcomes remains unclear. We discovered that pregnant women with antiphospholipid syndrome harbor a unique vaginal microbial community: they exhibit depletion of the protective species Lactobacillus johnsonii while showing enrichment of Bifidobacterium dentium , a bacterium typically found in the gut. Unlike typical vaginal infections that display widespread microbial dysbiosis, antiphospholipid syndrome induces only selective alterations in specific bacterial species. These microbial signatures correlated with hematological parameters and adverse pregnancy histories, including prior miscarriages. Our findings suggest that monitoring vaginal microbiota could provide a simple, noninvasive approach to identify high-risk pregnancies in women with antiphospholipid syndrome and may guide novel screening strategies for pregnancy-related disorders targeting the vaginal microbiome.

Gestational diabetes mellitus (GDM) has become a significant concern in the domain of women's health. The pathophysiology of GDM is complicated and not entirely understood. As a functional interface of the maternal and fetal metabolisms, it is evident that the placenta exerts an effect on the development of GDM. The placenta not only involves itself in insulin resistance via the production of hormones, but also serves as an organ abundant in mitochondria and exhibits intense metabolic activities, rendering it particularly vulnerable to the adverse effects of oxidative stress. In the high-glucose environment, excessive oxidative damage leads to mitochondrial dysfunction and further induces ferroptosis by facilitating lipid peroxidation. The objective of this review is to predominantly assess recent research, published within the last five years, that investigates the roles of placental oxidative stress, mitochondrial dysfunction, and ferroptosis as pathological mechanisms influencing the development of GDM. Understanding these pathological changes may help to better explore novel therapeutic strategies for GDM.

Hypertensive disorders of pregnancy (HDP) rank among the primary contributors to maternal and perinatal morbidity, characterized by hypertension, proteinuria, and neuropsychiatric manifestations. While metabolic dysfunction is recognized as a driving factor in various diseases, the precise characteristics of lipid metabolism dysfunction in HDP remain inadequately understood. Full-spectrum metabolomic profiling was performed on peripheral blood samples from 30 patients with HDP and 30 healthy controls, with targeted metabolic validation using placental tissues. RNA sequencing was employed to investigate the molecular characteristics underlying lipid metabolism dysregulation in HDP. Our findings highlight significant disruptions in lipid metabolism, particularly fatty acyls (FAs), in patients with HDP. The levels of specific FAs were closely associated with HDP clinical characteristics. Furthermore, RNA sequencing revealed a strong correlation between MCAM expression and FA metabolism, as well as HDP-related symptoms. KEGG pathway analysis and molecular biology experiments suggested the activation of MAPK pathway may be related with MCAM’s involvement in FA metabolism among patients with HDP. Our study provides insights into the characteristics of lipid metabolism dysfunction in HDP and delineates its potential molecular pathways.

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.