Recurrent spontaneous abortion (RSA) is associated with the dysregulation of type Ⅰ interferon (IFN-I) and inflammatory responses. Here, we revealed that IFN-Is and inflammation were upregulated in villus tissues from RSA patients, accompanied by elevated ring finger protein 145 (RNF145) levels and interferon regulatory factor 3 (IRF3) phosphorylation. Moreover, ectopic expression of RNF145 in human embryonic kidney 293 T cells augments IRF3-mediated signalling, leading to the production of IFN-Is and inflammatory cytokines. Mechanistically, RNF145 interacts with IRF3 and induces K63-linked polyubiquitination. Collectively, these findings indicate that RNF145 promotes IFN-I and inflammatory responses in RSA by enhancing IRF3-dependent signalling, highlighting its potential as a biomarker for risk prediction and a therapeutic target for RSA.

Congenital anomalies of the reproductive system represent a heterogeneous group of structural and functional abnormalities affecting both male and female genital organs. These anomalies typically arise during embryogenesis and may remain asymptomatic until they are incidentally identified during evaluation for infertility, recurrent pregnancy loss, or disorders of sexual development. In females, abnormalities include Müllerian duct anomalies and congenital malformations of the uterus, cervix, vagina, and ovaries, such as Mayer-Rokitansky-Küster-Hauser syndrome, septate, unicornuate, bicornuate, and didelphys uteri, and ovarian agenesis and undescended ovaries. In males, congenital conditions such as anorchia, cryptorchidism, hypospadias, ejaculatory duct obstruction, and ejaculatory dysfunction may be associated with impaired spermatogenesis and reduced fertility. Early recognition of these conditions may facilitate timely clinical evaluation and individualized management, which can include surgical correction, hormonal therapy, and reproductive counseling. When appropriate, early diagnosis may support multidisciplinary care, with the aim of optimizing sexual development, preserving reproductive potential, and reducing long-term morbidity associated with congenital anomalies. However, the clinical impact of early detection varies depending on the type and severity of the anomaly. A systematic and multidisciplinary approach may contribute to improved reproductive outcomes and better overall reproductive health in affected individuals. Further research is needed to better define the optimal timing and clinical utility of systematic evaluation strategies in this patient population.

This study aims to further clarify the correlation between the quantity of natural killer (NK) cells in the endometrium and the successful implantation of embryos during the specific implantation window. Patients were stratified into four distinct groups according to the quantity of natural killer (NK) cells detected during the implantation window. The groups were defined as follows: Group A (NK cell percentage ≥ 10%, n = 62), Group B (NK cell percentage: 5%-9.99%, n = 128), Group C (NK cell percentage: 1%-4.99%, n = 106), and Group D (NK cell percentage ≤ 0.5%, n = 30). Among Group A, 32 patients received intrauterine infusion of dexamethasone (designated as Subgroup A1), while the remaining 30 patients did not undergo this treatment (designated as Subgroup A2). For Groups B and D, immunohistochemistry was performed to detect the expression of IGFBP1 (an endometrial decidualization marker) and HBP1 (a decidualization-related transcription factor). The live birth rate in Group D was statistically significantly lower than that in the other three study groups. For Group A, after dexamethasone administration, a notable reduction in NK cell quantity was observed in Subgroup A1 (patients who received intrauterine dexamethasone infusion) during the implantation window; however, the pregnancy rates of Subgroup A1 and Subgroup A2 (patients without dexamethasone treatment) were comparable. Furthermore, in Group D patients, the expression levels of the decidualization markers IGFBP1 and HBP1 were significantly lower than those in the reference group (Group B, as specified in Methods). Insufficient natural killer (NK) cells during the embryo implantation window significantly impede the embryo implantation process. This shortage of NK cells may be attributed to inadequate endometrial decidualization. Notably, although intrauterine infusion of dexamethasone effectively reduces NK cell counts, it does not exert a significant impact on clinical outcomes.

Recurrent pregnancy loss (RPL) is a heterogeneous reproductive disorder in which dysregulation of maternal-fetal immune tolerance, aberrant decidual immune remodeling, and altered inflammasome signaling have been implicated within a complex multi-omics landscape. Multi-omics profiling (genomics, epigenomics, single-cell/spatial transcriptomics, proteomics, metabolomics, microbiome analyses, and immunomics) is increasingly being used to characterize mechanistic heterogeneity in RPL and to support biomarker discovery and immune-informed stratification. Genomic studies have associated chromosomal abnormalities and pathogenic variants with early embryonic developmental failure, while epigenomic profiling has highlighted aberrant methylation patterns and imprinting disturbances. Single-cell and spatial transcriptomics have revealed altered cellular composition and disrupted communication among decidual stromal cells, uterine natural killer (uNK) cells, macrophages, regulatory T cells (Treg), T helper 17 (Th17) cells, and trophoblast lineages. Proteomic and metabolomic studies have further identified immune-metabolic signatures associated with impaired trophoblast function and vascular remodeling, while emerging microbiome studies suggest a gut-reproductive axis that may modulate systemic immune homeostasis. Integration of multi-omics datasets with computational frameworks (e.g., weighted gene co-expression network analysis (WGCNA), multi-omics factor analysis (MOFA), and deep-learning models may improve RPL subtype classification, risk prediction, and the identification of potentially actionable pathways. However, current studies remain limited by small cohort sizes, especially in single-cell datasets, cross-platform heterogeneity, insufficient longitudinal validation, and a lack of multicenter reproducibility. Future work should prioritize standardized multi-omics pipelines, clearer evidence stratification, and immune-centric analytical frameworks to improve the robustness and translational relevance of RPL research. These advances may ultimately support immune-informed risk assessment and contribute to the gradual development of more individualized management strategies for RPL.

Trophoblasts, integral to placental function, are pivotal in implantation and in establishing the maternal-fetal interface. Abnormal proliferation and invasion of trophoblasts can significantly contribute to the onset and progression of recurrent spontaneous miscarriage. Tumor necrosis factor ligand superfamily member 3B (TNFSF13B) is a classical B-cell activating factor that plays an important role in regulating the proliferation, growth, differentiation and invasion of a variety of cells, and is involved in the pathogenesis of multiple human diseases. However, its role in unexplained recurrent miscarriage (URM) remains unclear. In the present study, we found that TNFSF13B expression was significantly decreased in trophoblast cells of villous tissue from unexplained recurrent miscarriage(URM) patients. TNFSF13B promoted the proliferation and invasion of HTR-8 cells. Using dual luciferase reporter and chromatin immunoprecipitation assays, we identified GATA-binding protein 3 (GATA3) as a key transcription factor that binds to the core promoter region of TNFSF13B and regulates TNFSF13B expression. Overexpression of F-box and WD-repeat domain-containing protein 7 (FBXW7) ubiquitin-degraded GATA3, resulting in decreased TNFSF13B expression. TNFSF13B regulates the proliferation and invasion of trophoblast cells through PI3K/Akt signaling pathway, which is inhibited and eventually leads to abortion. Taken together, our findings suggest that TNFSF13B, GATA3 and FBXW7 may be involved in the pathogenesis of URM and may serve as potential therapeutic targets.

As a major challenge currently plaguing reproductive medicine, recurrent pregnancy loss(RPL) has a variety of causes. Thyroid autoimmunity(TAI) is a prevalent thyroid disorder among women of childbearing age, potentially impacting maternal physiological changes and the balance of the maternal-fetal interface during pregnancy through endocrine and autoimmune pathways, which can lead to abortion and RPL. The selection of therapeutic agents and the effectiveness of treatment for patients experiencing RPL with thyroid autoimmunity remain contentious. Current research have explored the efficacy of medications such as levothyroxine, immunoglobulins, glucocorticoids, cyclosporine, hydroxychloroquine, selenium, and vitamin D for these patients. This review summarizes the correlation between TAI and RPL, as well as the current status of its diagnosis and treatment, with the aim of providing new ideas for clinical diagnosis and treatment.