American Journal of Reproductive Immunology最新文献

Problem: Natural killer (NK) cells are critical regulators of immune balance at the maternal-fetal interface. T-bet (Tbx21) is a key transcription factor shaping NK cell effector functions, yet its role in decidual NK (dNK) cell adaptation across gestation remains unclear.

Method of study: We used a T-bet fate-mapping mouse model (Rosa26^RFP × Tbx21^Cre) to track developmental and functional reprogramming of NK cells in the uterus, decidua, and placenta throughout pregnancy. Analyses included flow cytometry, bulk RNA sequencing of fate-mapped cells, and single-cell transcriptomic profiling of CD45+Lineage- immune populations at mid and late gestation.

Results: We found that NK cells with a history of T-bet expression (RFP+) progressively downregulate T-bet in a tissue and gestation-specific manner, particularly within decidual and placental compartments. Despite this loss, RFP+ cells retained core NK cell markers and altered their lineage identity towards ILC2 or ILC3 fate. Bulk transcriptomic analysis revealed that T-bet downregulation is associated with dampened IFN-γ, and cytotoxic pathways and increased expression of tissue-residency associated transcriptional regulators. Single-cell RNAseq revealed a gestational transition in dNK subset composition, with a decline in cytotoxic tissue-resident NK cells and expansion of regulatory and conventional NK subsets by late gestation.

Conclusions: These findings identify a novel transcriptional program that shapes NK cell plasticity in response to T-bet downregulation across gestation. Rather than undergoing lineage diversion, dNK cells adapt to the decidual environment via transcriptional compensation and subset redistribution during pregnancy. This work sheds light on the temporal coordination of innate immune function relevant to pregnancy success.

Problem: How does the traditional Chinese compound Bushen Xiaozheng Decoction (BSXZD) affect the immunosuppressive microenvironment in rat endometriosis models?

Methods: Sprague Dawley rats were randomly divided into normal, sham operation, model, Yasmin, and low-, medium-, high-dose BSXZD groups with 10 rats in each group. The endometriosis model was established by autologous endometrial transplantation, and corresponding interventions were given for 28 days. The volume of ectopic lesions was measured, and histological changes of endometrium were observed by hematoxylin-eosin staining. The protein or gene expression of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) in serum or endometrium was detected by immunohistochemistry, quantitative real-time polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay.

Results: Following treatment with BSXZD, the pseudostratified phenomenon and cavity structure of endometrial cells were reduced. Additionally, the expression levels of IL-10 and TGF-β in both endometrium and serum were significantly decreased, accompanied by a marked reduction in the volume of ectopic lesions.

Conclusion: BSXZD can significantly inhibit the growth of ectopic lesions in a rat model of endometriosis. The underlying mechanism may involve dual regulation of the endocrine-immune axis: it not only directly downregulates the expression of the immunosuppressive factors IL-10 and TGF-β to reversing the local immunosuppressive microenvironment, but also indirectly modulates these cytokines via sex hormone-related signaling pathways. Further studies are needed to clarify the precise molecular mechanism.

Problem: Recurrent pregnancy loss (RPL), defined as two or more consecutive pregnancy losses before 20 weeks of gestation, affects 1%-5% of couples of reproductive age worldwide. Growing evidence indicates a role for the microbiome in reproductive health, particularly in unexplained RPL.

Method of study: Based on a review of literature from PubMed, EMBASE, and Web of Science databases from January 2020 to September 2025, this comprehensive overview explores the current understanding of the link between microbiome dysbiosis and RPL.

Results: Microbiome dysbiosis, especially a reduction in Lactobacillus dominance and increased diversity, is strongly linked to RPL across multiple reproductive sites. RPL is associated with the loss of protective Lactobacillus crispatus and a higher presence of potentially harmful bacteria, including Gardnerella vaginalis and Atopobium vaginae. An altered gut microbiome, particularly with lipopolysaccharide-producing gram-negative bacteria, contributes to systemic inflammation and immune dysfunction by disrupting maternal-fetal immune tolerance. The microbiome-immune axis is essential for establishing maternal-fetal tolerance, with dysbiosis promoting pro-inflammatory Th1/Th17 responses while suppressing regulatory T cells. Multiple mechanisms connect microbiome dysbiosis to RPL, including local inflammation, systemic immune issues, disruption of maternal-fetal immune tolerance, molecular mimicry, and autoimmunity.

Conclusions: The microbiome is a promising new target for RPL treatment, with personalized microbial profiling and targeted therapies showing potential to improve pregnancy outcomes. Clinical implementation requires standardized protocols, larger randomized controlled trials, and validation of microbiome-targeted interventions.

Problem: Maternal obesity is associated with elevated inflammatory markers, hormonal dysregulation, and metabolic disturbances. However, how maternal obesity modulates systemic inflammatory, hormonal, and redox profiles in the peripartum and postpartum periods remains incompletely understood.

Method of study: This observational study evaluated inflammatory biomarkers, steroid hormone levels, and oxidative stress markers in obese (n = 8) and non-obese (n = 11) pregnant women undergoing labor induction. Peripheral maternal blood samples were collected immediately before induction and again within approximately 5-10 mins after delivery. Placental tissue was collected postpartum within the same interval. Comparative analyses between groups and time points were performed using repeated-measures statistical models.

Results: C-reactive protein (CRP) levels increased postpartum only in the obese group, indicating an enhanced inflammatory response after delivery. In contrast, interleukin-6 (IL-6) levels declined postpartum only in the non-obese group. No between-group differences were detected in the oxidative stress markers assessed, either in maternal blood or placental tissue.

Conclusions: Maternal obesity is associated with distinct postpartum inflammatory and hormonal profiles, characterized by sustained CRP elevation and altered cytokine dynamics. No between-group differences were detected in the redox markers assessed, suggesting preserved redox balance in the parameters evaluated. These findings highlight the importance of considering postpartum immune modulation in obese parturients and support further investigation into obesity-associated inflammatory regulation during the peripartum period.

Problem: Tissue-resident memory (T_RM) cells represent important immune sentinels that mount rapid recall responses to pathogens and cancers. However, there are limited data in humans on genital tract T_RM collected by clinically feasible sampling methods, limiting a full understanding of their role in immunity and clinical disease.

Method of study: We used flow cytometry and single cell RNA sequencing (scRNAseq) to characterize T cells isolated from ectocervical biopsies and endocervical cytobrushes collected from women attending a colposcopy clinic in Winnipeg, Canada.

Results: The ectocervix generally contained a higher frequency and abundance of immune cells and T-cells compared to the endocervix. CD4+ and CD8+ T_RM were more approximately 5-times more frequent and abundant in the ecto- compared to endocervix, even after accounting for higher T-cell recovery from the ectocervix. Phenotypically, CD4+ T_RM showed higher Th17- and comparable regulatory-associated marker expression compared to non-T_RM in both the ecto- and endocervix. Cervical dysplasia and ectropion were both associated with several immune cell differences in the ecto- and endocervix including lower CD4+ T_RM. Single-cell RNAseq analyses confirmed broad CD69 and core T_RM-related gene expression and captured several heterogeneous CD4+ and CD8+ T_RM subsets with diverse gene expression and pathways associated with host immunity, homeostasis, and nonimmune cell interactions.

Conclusions: Our data suggest that T_RM are more abundant in ecto- versus endocervical samples, which may reflect differences in commonly used sampling methods. Location and heterogeneous expression profiles underscore the need to better understand their role in microbial interactions, inflammation, and genital infection susceptibility in women.

Objective: Postmenopausal bleeding (PMB) and increased endometrial thickness are key clinical indicators that may suggest underlying malignancies. While endometrial biopsy remains the diagnostic gold standard, its invasiveness underscores the need for alternative, noninvasive biomarkers. This study evaluates the potential of clinical, laboratory, and peripheral blood inflammatory indices (PBII) in distinguishing malignant from benign endometrial pathologies.

Methods: This retrospective study included 162 patients who underwent endometrial biopsy due to PMB and/or increased endometrial thickness between January 2023 and January 2024. Patients were categorized into benign (n = 134) and malignant (n = 28) groups. Demographic, clinical, and laboratory parameters were collected, PBII parameters were calculated, and comparisons were performed. Logistic regression analyses were conducted to identify independent predictors of malignancy.

Results: Malignant cases were significantly associated with older age (p < 0.001), longer postmenopausal duration (p = 0.002), higher body mass index (BMI) (p = 0.018), and greater endometrial thickness (p = 0.042) compared to benign cases. Hemoglobin levels were significantly lower (p = 0.022), while neutrophil (p < 0.001) and monocyte (p = 0.042) counts were notably higher in malignant cases. Among PBII parameters, neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and systemic inflammation response index (SIRI) were significantly elevated (p < 0.001 for all). Multivariate analysis identified older age (p < 0.001), lower hemoglobin (p = 0.016), higher neutrophil count (p = 0.030), and increased PIV (p = 0.022) as independent predictors of malignancy.

Conclusion: Integrating clinical and laboratory parameters with PBII, particularly PIV, may be a valuable, noninvasive tool for the early detection and risk stratification of endometrial malignancies. This approach could enhance diagnostic accuracy, reduce the need for invasive biopsies, and improve patient management.