Background The morphological appearance of zona pellucida (ZP) is considered to be predictive of the quality of the oocytes and embryos. Agar-like ZP represents a common type of ZP abnormality, which is usually associated with significant defects in oocyte maturation and typically leads to unfavorable assisted reproductive technology (ART) outcomes. Currently, the intrinsic properties of agar-like ZP oocytes remain unclear, and effective strategies to improve the ART outcomes for such patients are still lacking.Methods We explored the intrinsic characteristics of metaphase I (MI)-arrest oocytes with agar-like ZP through RNA sequencing, immunofluorescence, and polarization microscope. Preemptive intracytoplasmic sperm injection (Pre-ICSI), i.e., performing ICSI on MI-arrest oocytes with agar-like ZP, was attempted, and its clinical outcomes were evaluated. What's more, we analyzed the potential mechanism of the effectiveness of Pre-ICSI.Results We uncovered the intrinsic nature of MI-arrest oocytes with agar-like ZP, revealing that these oocytes have inherently achieved nuclear and cytoplasmic maturation and should not be abandoned. Based on the fertilization and developmental potential of MI-arrest oocytes with agar-like ZP, we proposed Pre-ICSI as a targeted therapeutic strategy for such oocytes. Clinical results confirmed Pre-ICSI enabled the successful fertilization and development of these oocytes into available embryos, significantly improving the ART outcomes for patients with agar-like ZP. Further mechanical properties detection showed that the stiffness of agar-like ZP and narrow perivitelline space mechanically restrained the first polar body (PB) separating from the cytoplasm in space during the first meiosis. The mechanical intervention of Pre-ICSI, along with the dynamic changes in the cytoplasm post-insemination, provided space for the extrusion of PBs, thus facilitating the fertilization process.Conclusions MI-arrest oocytes with agar-like ZP possess intact nuclear and cytoplasmic maturation, representing a highly viable and valuable gamete pool rather than inherently defective discards. When managed with the targeted Pre-ICSI strategy, these oocytes can be successfully rescued, significantly improving the yield of available embryos and the overall success rate of IVF for these patients.

Extracellular vesicles (EVs) in the mammalian oviduct constitute a key maternal regulatory system that maintains redox balance during early embryogenesis, yet their molecular cargo and functional relevance in human embryos remain poorly defined. Here, we show that human Fallopian tube-derived EVs (oEVs) are rapidly internalized by human preimplantation embryos and improve developmental quality in vitro, increasing high-quality Day 3 embryo formation and blastocyst development. Label-free proteomics identified 6505 oEV proteins, with metabolic, antioxidant and stress-response pathways strongly enriched. Cross-reference with four independent datasets revealed a conserved protein subset shared across secretory-phase oviduct fluid, pluripotent stem cell-derived EVs and in-vivo-developed embryos; among these, YWHAZ was prioritized for functional validation because of its abundance in oEVs, its presence across embryo-related datasets, and its known involvement in stress-response pathways. We found that Ywhaz-deficient mouse embryos exhibit elevated oxidative and apoptotic stress, transcriptional signatures of impaired glutathione metabolism, and failure to survive to birth despite normal blastocyst morphology. Recombinant YWHAZ protein alone failed to enter intact embryos, whereas engineered YWHAZ-loaded EVs were efficiently internalized and significantly reduced intracellular ROS and apoptosis, restoring redox status towards in vivo levels without compromising implantation or foetal growth. Taken together, these findings identify YWHAZ protein as a conserved vesicle-delivered regulator of redox homeostasis and demonstrate that EV-mediated molecular delivery can partially rescue the oxidative stress burden characteristic of in vitro embryo culture. This work provides mechanistic insight into the maternal redox support system of the oviduct and establishes a foundation for EV-based engineering of next-generation embryo culture strategies. Fallopian tube extracellular vesicles enhance human IVF embryo development by delivering functional proteins such as YWHAZ to regulate oxidative stress and blastocyst formation. Large Scale Data Proteomic data are available in the PRIDE database under accession number PXD054946 (https://www.ebi.ac.uk/pride/). Ywhaz-KO embryo RNA-sequencing data are available in the GEO database under accession number GSE294735 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE294735.

The age-related decline in oocyte quality constitutes a major cause of reduced female fertility. In this study, we investigated the potential of stromal cell-derived factor-1 (SDF-1) to counteract oocyte deterioration during reproductive aging. We observed a significant negative correlation between SDF-1 levels and aging in both human follicular fluid/oocytes and murine ovarian tissues. Utilizing aged mouse models, we found that SDF-1 supplementation, both in vitro and in vivo, was associated with the amelioration of multiple aging-associated oocyte defects, including restored meiotic spindle morphology, improved chromosomal alignment, normalized distribution of cortical granules and mitochondria, enhanced mitochondrial membrane potential, and reduced oxidative stress. Consequently, SDF-1 treatment improved fertilization competence, embryonic developmental potential, and fertility restoration in aged female mice. Mechanistically, transcriptomic and functional analyses suggested that SDF-1 ameliorates oocyte aging primarily by enhancing autophagic activity, which was associated with clearance of accumulated stress granules and mitigation of oxidative damage. Pharmacological inhibition of autophagy attenuated the beneficial effects of SDF-1. In conclusion, our findings point to a previously underexplored role for SDF-1 in alleviating age-related oocyte decline, potentially through autophagy-enhanced stress granule scavenging, positioning SDF-1 as a promising candidate for therapeutic intervention in reproductive aging, although further investigations are warranted in the future.

OBJECTIVE:This study investigates the impact of a prolonged time interval between sibling embryo transfers on clinical pregnancy outcomes, utilizing a model that controls for oocyte aging to isolate maternal time-dependent factors. DESIGN:This retrospective, single-center, self-controlled cohort study evaluated patients who underwent at least two distinct embryo transfers utilizing sibling embryos derived from a single oocyte retrieval cycle between January 2013 and June 2024. The exposure group comprised subsequent transfers performed after an interval exceeding 36 months. Clinical outcomes, including implantation, biochemical pregnancy, clinical pregnancy, early miscarriage, and live birth rates, were compared. RESULTS:The final analysis included 2008 cycles from 654 couples (877 initial control cycles and 1131 subsequent exposure cycles). Following logistic regression analyses to adjust for potential confounders, the subsequent transfer group exhibited significantly decreased likelihood of biochemical pregnancy (adjusted odds ratio [OR] 0.60, 95% confidence interval [CI] 0.46-0.77, P < 0.001), clinical pregnancy (adjusted OR 0.49, 95% CI 0.38-0.63, P < 0.001) and live birth (adjusted OR 0.52, 95% CI 0.41-0.66, P < 0.001). To further minimize embryological bias, a highly restricted subgroup analysis was performed on single, good quality day 5 blastocyst transfers utilizing artificial endometrial preparation protocols (144 control vs. 163 exposure cycles). Within this subgroup, the subsequent transfers continued to demonstrate significantly inferior outcomes, with notable reductions in implantation, biochemical pregnancy, clinical pregnancy, and live birth rates (all P < 0.001). CONCLUSION:A prolonged interval (>36 months) between sibling embryo transfers independently and negatively impairs clinical pregnancy outcomes. For patients planning subsequent pregnancies using cryopreserved sibling embryos, it is clinically advisable to proceed with the transfer as early as medically appropriate to mitigate the time-dependent degradation of the reproductive environment.

Three patients with genetically confirmed female subfertility due to heterozygous likely pathogenic variants in TUBB8 (c.613G > A), ZP2 (c.1421T > C), or ZP3 (c.518 C > G), respectively, had histories of recurrent adverse assisted reproductive technology (ART) outcomes, including zona pellucida (ZP) abnormalities or oocyte degeneration, reduced fertilization, poor embryo development or limited viable embryo availability, and implantation failure. Notably, all three patients eventually achieved successful live births. Patient 1, after two failed ART cycles, delivered a male infant following a third ICSI attempt, and later conceived naturally, delivering a female infant. Patient 2, after five unsuccessful IVF/ICSI cycles and no implantation, conceived naturally years later and delivered a male infant. Patient 3, following two failed IVF/ICSI attempts, conceived via donor oocytes and later delivered a male infant through natural conception. These cases expand the reported reproductive outcome spectrum of women carrying likely pathogenic variants in oocyte- and ZP-related genes. The findings suggest that reproductive outcomes in selected heterozygous carriers may be more variable than previously appreciated and that residual reproductive potential may occasionally be retained. These observations may help refine reproductive genetic counseling for women with genetically associated subfertility, while further case accumulation and functional studies are required.

Oocyte developmental competence depends not only on nuclear maturation but also on cytoplasmic functions required for fertilization and early embryogenesis. The endoplasmic reticulum (ER) is the major intracellular calcium store in mammalian oocytes and acts as a spatial organizer of cytoplasmic maturation. ER-associated features are increasingly discussed in relation to in vitro maturation, aging, cryopreservation, fertilization failure, and visible smooth endoplasmic reticulum aggregates, but their biological and clinical meanings are not always clearly understood. This review integrates evidence on ER remodeling during oocyte maturation and its relevance to oocyte quality in assisted reproduction. During meiotic maturation, the ER undergoes stage- and species-specific reorganization that supports calcium-store positioning, inositol 1,4,5-trisphosphate receptor-dependent calcium release, and activation competence. ER remodeling during maturation is also linked to cytoskeletal organization, mitochondrial function, lipid handling, plasma-membrane Ca2+ influx, and degradative quality-control systems. These interfaces place ER remodeling within a broader multi-organelle network rather than a single calcium-signaling pathway. ER homeostasis and unfolded protein response (UPR) signaling contribute to cytoplasmic quality, whereas excessive ER stress can impair maturation through calcium imbalance, mitochondrial dysfunction, and defective stress adaptation. In clinical and laboratory settings, altered ER or smooth endoplasmic reticulum (SER)-related features may reveal cytoplasmic vulnerability after in vitro maturation, cryopreservation, aging, or fertilization failure, but they should not be interpreted as isolated or deterministic markers of oocyte competence. ER remodeling links oocyte maturation biology with several clinically relevant features of oocyte quality in assisted reproduction. Its translational value will depend on integrating structural observations, calcium-signaling competence, maturation history, and developmental endpoints while maintaining clear boundaries between mechanistic evidence and clinical decision-making.

While serum luteinizing hormone (LH) on the day of trigger is a conventional predictor of in vitro fertilization (IVF) outcomes, its clinical utility remains inconsistent. This study aimed to evaluate the serum LH/large follicle (LH/LF) ratio as a refined risk-stratification marker for reproductive outcomes in IVF/ICSI cycles. A retrospective cohort study was conducted involving 8,329 first fresh IVF/ICSI cycles. Multivariable logistic regression models, adjusted for maternal age, body mass index (BMI), anti-Müllerian hormone (AMH), basal antral follicle count (Basal AFC), endometrial thickness, number of embryos transferred, and embryo developmental stage, evaluated the independent associations of the LH/LF ratio with the probability of clinical pregnancy and live birth. Predictive performance was compared with absolute LH levels using receiver operating characteristic (ROC) curves and the DeLong test. The LH/LF ratio was identified as a significant independent negative predictor of clinical pregnancy (OR = 0.589, 95

At present, the known genetic causes of abnormal oocyte development can only account for a minority of female infertility. In our previous study, the mutation c.1101 C > G, p.Tyr367* in discs large-associated protein 5 (DLGAP5) was identified as a novel genetic cause of human oocyte maturation abnormality and female infertility. The present study aimed to validate the function of DLGAP5 in oocyte maturation and further explore the underlying mechanism by which DLGAP5 regulates oocyte meiosis. Cell experiments elucidated that DLGAP5 participates in cell division, and its depletion induced G2/M arrest. The depletion of DLGAP5 in human oocytes by microinjection of siRNAs resulted in abnormal spindle morphology and oocyte maturation defects, exhibiting reduced germinal vesicle breakdown and polar body 1 extrusion rate. In addition, a similar phenotype of abnormal oocyte development was observed in Dlgap5-deficient mouse oocytes, which could be rescued by DLGAP5 cRNA microinjection. Furthermore, single-cell RNA Sequencing showed Dlgap5 knockout altered expression of genes involving in meiosis process in oocytes and deactivated PI3K-AKT signaling pathway. And PI3K-AKT activators facilitated the oocyte maturation resumption in Dlgap5-deficient mice. DLGAP5 has been demonstrated to regulate the process of oocyte maturation via the activation of PI3K-AKT pathway. It reinforces the significant role of DLGAP5 function in oocyte maturation regulation and reveals the underlying mechanism. It provides crucial insights into clinical consultation, genetic diagnosis, and treatment strategies among infertile patients.

Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with impaired female fertility, as suggested by our previous clinical cohort data. However, the intrinsic mechanisms underlying oocyte quality deterioration remain incompletely understood. Using a chronic SLE mouse model, we show that SLE-associated inflammation is accompanied by impaired oocyte maturation, reduced developmental competence, and mitochondrial dysfunction, together with increased oxidative stress and ferroptosis-related alterations, an iron-dependent process characterized by lipid peroxidation. Pharmacological interventions revealed that both hydroxychloroquine and melatonin attenuated inflammation- and oxidative stress-associated abnormalities and partially improved oocyte developmental outcomes. In addition, inhibition of ferroptosis using ferrostatin-1 ameliorated ferroptosis-associated alterations and partially restored meiotic maturation and oocyte quality. Together, these findings establish a mechanistic link between SLE-induced inflammation, oxidative stress, ferroptosis, and impaired oocyte developmental competence. These results provide a framework for understanding inflammation-associated oxidative stress and ferroptosis-related alterations in SLE-associated reproductive dysfunction and may inform future therapeutic exploration.

Background This study aimed to describe carrier findings, genetic counseling recommendations, and subsequent ART plan choices observed after untargeted whole-exome sequencing (WES)-based carrier screening in infertile Chinese Han couples attempting assisted reproductive technology (ART). Methods This retrospective, exploratory, single-center descriptive study included infertile couples who had undergone genetic counseling and WES for carrier screening in an in vitro fertilization (IVF) clinic affiliated with a university in Central China. Genetic findings, counseling recommendations, and ART plans documented after WES were summarized descriptively. No comparator group, validated decision-making survey instrument, or pre-specified before-after decision outcome was available. Results A total of 130 infertile or subfertile couples were enrolled. Overall, 82.7% (215/260; 95% CI 77.6-86.8%) of individuals carried at least one P/LP variant, including 77.7% (101/130; 95% CI 69.8-84.0%) of males and 87.7% (114/130; 95% CI 80.9-92.3%) of females. The carrier burden was 1.6038 variants per person. GJB2-associated deafness was the most prevalent finding, occurring in 13.8% (36/260) of individuals. After excluding somatic and autosomal-dominant secondary findings from the reproductive carrier-risk denominator, 7.7% (10/130; 95% CI 4.2-13.6%) of couples met the strict AR/XL at-risk-couple definition. Among these 10 couples, PGT-M was recorded as the post-WES ART plan for three couples (30.0%; 95% CI 10.8-60.3%). Conclusion In this retrospective descriptive cohort, WES-based carrier screening identified a high carrier burden and generated counseling recommendations that were followed by different ART plan choices among AR/XL at-risk couples. Genetic counseling before and after WES remains important for couples receiving positive carrier-screening results.

This study investigated the molecular mechanisms through which tauroursodeoxycholic acid (TUDCA) improves the in vitro maturation (IVM) efficiency of aged oocytes, utilizing germinal vesicle (GV)-stage oocytes from aged (45-week-old) and young (6-week-old) mice, as well as human oocytes from women aged ≥ 38 and ≤ 30 years. Microproteomic analysis revealed that aging oocytes exhibit significantly exacerbated endoplasmic reticulum stress (ERS) during IVM, leading to reactive oxygen species accumulation and mitochondrial dysfunction. Treatment with 100 μM TUDCA attenuated ERS and consequently suppressed ERS-induced activation of the PERK-eIF2α-CHOP pathway, significantly enhancing the first polar body extrusion rate while reducing spindle abnormalities in aged oocytes. Furthermore, TUDCA improved mitochondrial function and decreased ROS accumulation in IVM-treated oocytes, thereby enhancing post-fertilization embryo developmental potential. In human oocyte IVM experiments, TUDCA likewise enhanced oocyte maturation in women of advanced maternal age and alleviated endoplasmic reticulum stress. These findings suggest that TUDCA may improve IVM outcomes in aged oocytes, potentially through modulation of key ERS pathways, and provide an experimental basis for optimizing related culture strategies in assisted reproductive technology (ART) for women of advanced maternal age (AMA).

To screen drug targets of ovarian aging from a genetic perspective. Systematic analyses were conducted with cis-expression quantitative trait loci data of druggable genes extracted as instrument variables. Summary statistics were from large genome-wide association studies for age at menopause. The following colocalization analysis was utilized to examine whether identified genes and ovarian aging shared causal variants. Furthermore, clinical validation was conducted by comparing expression of identified genes in granulosa cells from women with normal or diminished ovarian reserve (DOR) who went through in vitro fertilization (IVF) and by evaluating correlation of targeted gene expression with ovarian function and IVF outcomes. Moreover, single-nuclear RNA (snRNA) seq and drug database were analyzed to find target cells within the ovary and potential drugs targeting identified genes. Systematic analyses identified five therapeutic targets of ovarian aging, including four protective factors (BRCA1, KLHL18, PNP, SRPK1) and one risk factor (PDIA3). The change in expression level of four protective factors has been verified in clinical validation. Particularly, both BRCA1 and SRPK1 have been downregulated among advanced-aged women with DOR and were positively correlated with anti-Müllerian hormone and antral follicle count. Specific target cells and potential small molecule targeted drugs of these genes were identified through snRNA analysis and searching in the drug database. By systematic genetic analyses combined with clinical validation, we identified five potential druggable genes for ovarian aging, providing theoretical basis and promising direction of therapeutic genetic targets for ovarian aging in the future.

BACKGROUND:The alveolar epithelial type II cell (AT2) and its senescence play a pivotal role in alveolar damage and pulmonary fibrosis. Cell circadian rhythm is strongly associated with cell senescence. Differentiated embryonic chondrocyte expressed gene 1 (DEC1) is a very important circadian clock gene. However, the role of DEC1 in AT2 senescence and pulmonary fibrosis was still unclear. RESULTS:In this study, a circadian disruption model of light intervention was used. It was found that circadian disruption exacerbated pulmonary fibrosis in mice. To understand the underlying mechanism, DEC1 levels were investigated. Results showed that DEC1 levels increased in lung tissues of IPF patients and in bleomycin-induced mouse fibrotic lungs. In vitro study revealed that bleomycin and TGF-β1 increased the expressions of DEC1, collagen-I, and fibronectin in AT2 cells. Inhibition of DEC1 mitigated bleomycin-induced fibrotic changes in vitro and in vivo. After that, cell senescence was observed in bleomycin-treated AT2 cells and mouse models, but these were prevented by DEC1 inhibition. At last, p21 was confirmed having circadian rhythm followed DEC1 in normal conditions. But bleomycin disrupted the circadian rhythm and increased DEC1 which promoted p21 expression, increased p21 mediated AT2 senescence and pulmonary fibrosis. CONCLUSIONS:Taken together, circadian clock protein DEC1 mediated pulmonary fibrosis via p21 and cell senescence in alveolar epithelial type II cells.

Pannexin1 (PANX1) is a highly glycosylated membrane channel-forming protein, which has been found to implicate in multiple physiological and pathophysiological functions. Variants in the PANX1 gene have been reported to be associated with oocyte death and recurrent in vitro fertilization failure. In this study, we identified a novel heterozygous PANX1 variant (NM_015368.4 c.410 C > T (p.Ser137Leu)) associated with the phenotype of oocyte death in a non-consanguineous family, followed by an autosomal dominant (AD) mode. We explored the molecular mechanism of the novel variant and the variant c.976_978del (p.Asn326del) that we reported previously. Both of the variants altered the PANX1 glycosylation pattern in cultured cells, led to aberrant PANX1 channel activation, affected ATP release and membrane electrophysiological properties, which resulted in mouse and human oocyte death in vitro. For the first time, we presented the direct evidence of the effect of the PANX1 variants on human oocyte development. Our findings expand the variant spectrum of PANX1 genes associated with oocyte death and provide new support for the genetic diagnosis of female infertility.

Recryopreservation (recryo) is occasionally applied in clinical, while the underlying mechanism of impaired clinical outcomes after recryo remains unclear. In this study, frozen embryo transfer (FET) cycles of single blastocyst transfer in an academic reproductive medicine center were enrolled. According to the number of times blastocysts experienced cryopreservation, they were divided into the cryopreservation (Cryo) group and the Recryo group. Donated human blastocysts were collected and detected for mechanism exploration. It was found that recryo procedure resulted in impaired blastocyst developmental potential, including decreased implantation rate, reduced biochemical pregnancy rate, declined clinical pregnancy rate, higher early miscarriage rate, and lower live birth rate. Moreover, recryo led to impaired trophectoderm (TE) function, exhibiting lower human chorionic gonadotropin levels 12 days after FET. In addition, single-cell RNA sequencing showed that the expression of genes involved in cell adhesion and embryo development were altered. More specifically, activated endoplasmic reticulum (ER) pathway and induced apoptosis were further verified by immunofluorescence and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay involving in the recryo procedure. In conclusion, recryo could interfere with the process of blastocyst implantation by impairing TE function, affecting blastocyst adhesion, activating ER stress pathway and inducing apoptosis. It provides caution to embryologists about the potential risk of recryopreservation.

Early embryo arrest is characterized by premature termination of development in preimplantation embryos. Human subcortical maternal complex (SCMC) is a protein complex that is specifically expressed in mammalian oocytes and early embryos and is essential for embryonic cell division. Peptidyl arginine deiminase 6 (PADI6) is proven to be a member of SCMC. Variants in the PADI6 gene have been shown to induce early embryo arrest. In this study, we performed genetic analysis in patients with female infertility due to early embryo arrest to identify the disease-causing gene variants. Whole-exome sequencing and Sanger sequencing were used to identify the variants in the patients and their families. Western blotting and immunofluorescence staining were used to check the effects of the variants on expression and function of PADI6. We identified a novel homozygous variant (c.358A > C [p.Thr120Pro]) and novel compound-heterozygous variants (c.2044C > T [p.Arg682Trp] and c.707dupT [p.Leu237Alafs*24]) in PADI6 in two infertile individuals with early embryo arrest. We found that these variants resulted in a decrease in the expression level of PADI6, which may lead to abnormal protein function. Immunofluorescence staining also suggested that these variants affected the expression of PADI6. Our study expands the spectrum of genetic defects in female early embryo arrest and further supports the causality between PADI6 variants and female infertility.

Previous studies investigating the relationship between systemic lupus erythematosus (SLE) and primary ovarian failure (POF) generated conflicting results. To data, no mendelian randomization study has been applied to examine this association. In this study, genetic instruments for exposure (SLE) were selected from a GWAS study with 5201 cases and 9066 noncases. Outcome data for POF and three reproductive traits (age at menarche, age at menopause, and age at first live birth) were obtained from other eligible GWASs. To estimate causal association, the inverse-variance weighted (IVW) method (the main analyse), MR Egger test, weighted median, simple mode, and weighted mode were applied. Moreover, sensitivity analyses were conducted to ensure the robustness of the results. Estimated by the IVW method, SLE was suggested to be causally related to the risk of POF (OR = 1.166, 95% CI 1.055–1.289, P = 0.003) and delayed age at first live birth (OR = 1.006, 95% CI 1.002–1.010, P = 0.007), with no evidence of a causal association between SLE and age at menopause or menarche. The estimates were robust according to sensitivity analysis. In conclusion, the two-sample MR study supported a causal association between SLE and POF from a genetic aspect.

Interleukin-10 (IL-10), a pivotal anti-inflammatory cytokine, has gotten attention for its involvement in tissue remodeling and organ fibrosis. Pleurisy and subsequent pleural remodeling are recognized as quantifiable indicators of systemic lupus erythematosus (SLE) activity. However, the role of IL-10 in SLE-associated pleural remodeling remains unknown. In this study, we investigated role of IL-10 in SLE-associated pleural remodeling and the underlying mechanism. Clinical data and serum specimens were obtained from SLE patients, while pleural mesothelial cells and mouse models served as primary experimental subjects. The protein expression-related technologies, histopathological staining, and other experimental methods were used in the study. Our investigation got several key findings. Firstly, serum obtained from SLE patients with pleural thickening was found to induce pleural mesothelial cell remodeling. Subsequently, heightened levels of IL-10 were found in serum from SLE patients with pleural thickening compared to that of SLE patients without pleural thickening. Secondly, administration of recombinant IL-10 was confirmed its ability to induce pleural mesothelial cell remodeling, on the contrary, this remodeling was effectively mitigated by IL-10 inhibition. Notably, blockade of IL-10 significantly prevented collagen deposition and prevented thickening in pleura of SLE mouse models. Lastly, the IL-10/JAK2/STAT3/HIF1α/TMEM45A/P4HA1 signaling axis was elucidated to mediate pleural remodeling and thickening. Our study uncovered that IL-10 mediated pleural remodeling in SLE. We suggested that serum IL-10 level exceeding 6.32 pg/mL was a potential reference threshold for predicting pleural thickening in SLE patients.