Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic diseases among women of reproductive age. Inflammation may be involved in the pathogenesis of PCOS, but its exact relationship with PCOS remains unclear. Herein, we investigate the causal association between systemic inflammatory regulators and PCOS risk through a two-sample Mendelian randomization (MR) approach based on the latest and largest genome-wide association study (GWAS) of 41 systemic inflammatory regulators in 8293 Finnish participants and a GWAS meta-analysis consisting of 10,074 PCOS cases and 103,164 controls of European ancestry. Our results suggest that higher levels of IL-17 and SDF1a, as well as lower levels of SCGFb and IL-4, are associated with an increased risk of PCOS (OR = 1.794, 95% CI = 1.150 – 2.801, P = 0.010; OR = 1.563, 95% CI = 1.055 – 2.315, P = 0.026; OR = 0.838, 95% CI = 0.712 – 0.986, P = 0.034; and OR = 0.637, 95% CI = 0.413 – 0.983, P = 0.042, respectively). In addition, genetically predicted PCOS is related to increased levels of IL-2 and VEGF (OR = 1.257, 95% CI = 1.022 – 1.546, P = 0.030 and OR = 1.112, 95% CI = 1.006 – 1.229, P = 0.038, respectively). Our results indicate the essential role of cytokines in the pathogenesis of PCOS. Further studies are warranted to assess the possibility of these biomarkers as targets for PCOS prevention and treatment.

Objectives Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disease characterised by the presence of antiphospholipid antibodies in circulation and pathological pregnancy. However, the pathogenesis of OAPS remains unknown. We aimed to reveal cellular compositions and molecular features of decidual cells involved in the development of OAPS using single-cell RNA sequencing (scRNA-seq). Methods We performed unbiased scRNA-seq analysis on the first-trimester decidua from five OAPS patients and five healthy controls (HCs), followed by validations with flow cytometry, immunohistochemical staining and immunofluorescence in a larger cohort. Serum chemokines and cytokines were measured by using ELISA. Results A higher ratio of macrophages but a lower ratio of decidual natural killer (dNK) cells was found in decidua from OAPS compared with HCs. Vascular endothelial cells shrinked in OAPS decidua while having upregulated chemokine expression and conspicuous responses to IFN-γ and TNF-α. Macrophages in OAPS had stronger phagocytosis function, complement activation signals and relied more on glycolysis. dNK cells were more activated in OAPS and had enhanced cytotoxicity and IFN-γ production. Downregulation of granules in OAPS dNK cells could be associated with suppressed glycolysis. Moreover, stromal cells had a prosenescent state with weakened immune surveillance for senescent cells in OAPS. In addition, the cellular interactions between decidual immune cells and those of immune cells with non-immune cells under disease state were altered, especially through chemokines, IFN-γ and TNF-α. Conclusion This study provided a comprehensive decidual cell landscape and identified aberrant decidual microenvironment in OAPS, providing some potential therapeutic targets for this disease.

Collagen, the main component of mammal skin, has been traditionally used in leather manufacturing for thousands of years due to its diverse physicochemical properties. Collagen is the most abundant protein in mammals and the main component of the extracellular matrix (ECM). The properties of collagen also make it an ideal building block for the engineering of materials for a range of biomedical applications. Reproductive medicine, especially human fertility preservation strategies and reproductive organ regeneration, has attracted significant attention in recent years as it is key in resolving the growing social concern over aging populations worldwide. Collagen-based biomaterials such as collagen hydrogels, decellularized ECM (dECM), and bioengineering techniques including collagen-based 3D bioprinting have facilitated the engineering of reproductive tissues. This review summarizes the recent progress in applying collagen-based biomaterials in reproductive. Furthermore, we discuss the prospects of collagen-based materials for engineering artificial reproductive tissues, hormone replacement therapy, and reproductive organ reconstruction, aiming to inspire new thoughts and advancements in engineered reproductive tissues research. Graphical abstract

Background: Hydroxychloroquine (HCQ) has been used in the treatment of systematic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), but its effect on lupus activity during pregnancy, preeclampsia and intrauterine growth restriction (IUGR) remains unclear. Methods: PubMed, Embase and Cochrane databases were searched before 11 September 2022 for randomized clinical trials (RCT) or observational studies involving additional HCQ treatment and pregnant women diagnosed as having SLE and/or APS/positive antiphospholipid antibodies (aPLs). Risks of high lupus activity, preeclampsia and IUGR were explored. Results: One RCT and 13 cohort studies were included. A total of 1764 pregnancies were included in the pooled meta-analysis (709 in the HCQ group vs. 1055 in the control group). After the additional use of HCQ, the risk of high lupus activity decreased (RR: 0.74, 95% CI: 0.57–0.97, p = 0.03). For preeclampsia, the total incidence decreased (RR: 0.54, 95% CI: 0.37–0.78, p = 0.001). The subgroup analysis showed statistical significance in the SLE subgroup (RR: 0.51, 95% CI: 0.34–0.78, p = 0.002) but not in the APS/aPLs subgroup (RR: 0.66, 95% CI: 0.29–1.54, p = 0.34). For IUGR, the decrease in incidence was not statistically significant (RR: 0.80, 95% CI: 0.47–1.35, p = 0.46), neither in the SLE subgroup (RR: 0.74, 95% CI: 0.40–1.36, p = 0.33) nor in the APS/aPLs subgroup (RR: 1.26, 95% CI: 0.34–4.61, p = 0.73). Conclusion: The additional use of HCQ may decrease the risk of high lupus activity during pregnancy and the incidence of preeclampsia for SLE patients, but the results do not support that using HCQ decreases the incidence of preeclampsia for APS/aPLs patients or reduces IUGR risk for SLE and/or APS/aPLs patients.