Polycystic ovary syndrome (PCOS), a complex endocrine and metabolic disorder, involves significant dysregulation of the immune system. Natural killer (NK) cells, as key components of innate immunity, demonstrate notable phenotypic and functional alterations in women with PCOS. These changes include not only an elevated proportion in peripheral blood but also dynamic shifts within the local microenvironments of the ovary and endometrium. The increased level of peripheral NK cells correlates with a chronic low-grade inflammatory state, potentially serving as a predictive marker in infertile PCOS patients. Within the endometrium, uterine NK (uNK) cells exhibit reduced numbers and impaired function, accompanied by dysregulation of cytokine networks such as IL-15 and IL-18, which disrupts the immune equilibrium essential for embryo implantation. Abnormal NK cell function further involves alterations in killer immunoglobulin-like receptor (KIR) repertoires and dysregulated secretion of angiogenic factors, thereby compromising endometrial receptivity and vascular remodeling. Hyperandrogenemia modulates the distribution and activity of NK cells in reproductive tissues by influencing their surface activation markers, while insulin resistance promotes the generation of myeloid-feature NK (myNK) cell subsets via the IL-6/Stat3 signaling pathway, collectively exacerbating metabolic inflammation and reproductive dysfunction. Deciphering the role of NK cells in the immunometabolic interplay of PCOS reveals their position as a critical link between. May represent a potential cutoff requiring validation in larger cohorts reproductive impairment and metabolic disturbances, opening new avenues for targeted immunomodulatory interventions. Collectively, NK cells appear to present an important immunometabolic link between reproductive dysfunction and metabolic disturbance in PCOS, highlight their potential relevance as therapeutic targets.
Jiang N, Liu J, Li C, Wang X, Pang Y, Zhang X, Ma Y, Zhang S, Xu Y, Li Q, Sun Q, Tang P, Han L. Natural killer cell dysregulation in polycystic ovary syndrome: immunometabolic and reproductive implication. Frontiers in immunology. 2026;17:1781451. doi:10.3389/fimmu.2026.1781451
Jiang, N., et al. "Natural killer cell dysregulation in polycystic ovary syndrome: immunometabolic and reproductive implication." Frontiers in immunology, vol. 17, 2026, pp. 1781451.
Regulatory T cells (Tregs) play a central role in maintaining immune tolerance and supporting maternal-fetal homeostasis throughout human pregnancy. Clinical and experimental evidence demonstrates that dysregulation of peripheral and decidual Tregs manifested as quantitative deficits, impaired suppressive function or lineage instability increased the risk of various pathological pregnancies, such as recurrent implantation failure (RIF), recurrent spontaneous abortion (RSA), pre-eclampsia (PE) and preterm birth (PTB). Recently, novel therapeutic strategies targeting Tregs have emerged in oncology, transplantation, and autoimmune diseases. However, their application in pathological pregnancy remains in its infancy. This review outlines the spatiotemporal dynamics of peripheral and decidual Tregs throughout gestation, elucidating their roles in maintaining maternal-fetal homeostasis and their dysregulation in pathological pregnancies. We also critically evaluated the therapeutic strategies targeting Tregs and Tregs-associated signaling pathways, including hormonal support, traditional intravenous immunoglobulin, as well as emerging interventions such as immunometabolic reprogramming and engineered cellular therapies like chimeric antigen receptor Tregs. This review may provide insights for understanding the roles of Tregs in physiological and pathological pregnancy, as well as provide new idea in the immunotherapy of pathological pregnancy.
Chronic Endometritis · Treatment of Chronic Endometritis
[BACKGROUND] Chronic endometritis (CE) has been widely recognized as a potential cause of infertility, however, access to effective treatment is a formidable challenge due to the rudimentary understanding of the pathogenesis of persistent CE. Here, we aimed to analyze the impact of platelet-rich plasma (PRP) treatment on pregnancy outcomes and the endometrial microenvironment in patients with persistent CE. [METHODS] A total of 89 infertility patients were selected, including 56 non-CE (as the control group) and 33 persistent CE. The persistent CE patients received an intrauterine infusion of PRP four times before embryo transfer. Immunohistochemistry staining and transcriptomic sequencing were used to investigate the uterine-specific role of PRP in patients with persistent CE. [RESULTS] The implantation rate and clinical pregnancy rate were significantly increased in the cured CE group compared to the non-cured CE group. After PRP treatment, the proportions of endometrial CD8+ T cells, CD56+ NK cells, Foxp3+ Treg cells, and T-bet+ Th1 cells were significantly decreased in patients with persistent CE. Specifically, DEG analysis showed that genes implicated in endometrial receptivity-related and antimicrobial were upregulated and genes involved in the immune response processes were downregulated in cured CE patients after PRP treatment. Functional enrichment analysis suggested that the effects of changes in leukocyte chemotaxis-related genes played a critical role in the endometrial immune environment. [CONCLUSIONS] Autologous PRP treatment has been shown as a potentially successful therapy for improving pregnancy outcomes by reconstructing the uterine local immune microenvironment to improve endometrial receptivity in patients with persistent CE.
Senthilkumar H et al., 2025·Journal of translational medicine
Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects reproductive-aged women worldwide, causing hormonal imbalances and ovarian dysfunction. PCOS affects metabolic health and increases the risk of obesity, insulin resistance, and cardiovascular disease, in addition to infertility. This review delves deeper into the connections of gut microbiota with PCOS pathophysiology, particularly into its impact on hormone metabolism, obesity, inflammation, and insulin resistance by way of short-chain fatty acids, lipopolysaccharides, and gut-brain axis. Studies also show that changes in the metabolic processes and immune responses are seen in changes in the gut microbiota in PCOS subjects, such as changes in the Bacteroidetes and Firmicutes groups. Some bacteria, like Escherichia and Shigella, have been associated with dysbiosis in patients with PCOS, leading to systemic inflammation and changed hormone levels, which further worsen the clinical symptoms. Therapeutic interventions targeting the gut microbiota comprise probiotics, prebiotics, and fecal microbiota transplantation; these have potential to alleviate the symptoms of PCOS. Other precision microbiome-based therapies include postbiotics, and CRISPR-Cas9 genome editing, which are relatively new avenues toward precision treatment. This complex interlink of gut microbiota and PCOS pathophysiology will open the avenues for possible treatments for hormonal imbalances and metabolic problems that characterize these complex disorders. The review here focuses on the requirement of further studies to be able to elucidate the specific pathways relating gut microbiota dysregulation to PCOS and, thus, improve microbiome-based therapies for better clinical outcomes in affected individuals.
Garmendia JV et al., 2025·International journal of molecular sciences·
Open Access
Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more consecutive pregnancy losses before 24 weeks of gestation. It affects 3-5% of women who are attempting to conceive. RPL can stem from a variety of causes and is frequently associated with psychological distress and a diminished quality of life. By contrast, recurrent implantation failure (RIF) refers to the inability to achieve a successful pregnancy after three or more high-quality embryo transfers or at least two instances of egg donation. RIF shares several causative factors with RPL. The immunological underpinnings of these conditions involve alterations in uterine NK cells, reductions in M2 macrophages and myeloid-derived suppressor cells, an increased Th1/Th2 ratio, a decreased Treg/Th17 ratio, the presence of shared ≥3 HLA alleles between partners, and autoimmune disorders. Various therapeutic approaches have been employed to address these immunological concerns, achieving varying degrees of success, although some therapies remain contentious within the medical community. This review intends to explore the immunological factors implicated in RPL and RIF and to analyze the immunological treatments employed for these conditions, which may include steroids, intravenous immunoglobulins, calcineurin inhibitors, anti-TNF antibodies, intralipid infusions, granulocyte colony-stimulating factor, and lymphocyte immunotherapy.