Inflammasomes are multi-protein complexes localized within immune and non-immune cells that induce caspase activation, proinflammatory cytokine secretion, and ultimately pyroptosis—a type of cell death. Inflammasomes are involved in a variety of human diseases, especially acute or chronic inflammatory diseases. In this review, we focused on the strong correlation between the NLRP3 inflammasome and various reproductive diseases, including ovarian aging or premature ovarian insufficiency, PCOS, endometriosis, recurrent spontaneous abortion, preterm labor, pre-eclampsia, and male subfertility, as well as the multifaceted role of NLRP3 in the pathogenesis and treatment of these diseases. In addition, we provide an overview of the structure and amplification of inflammasomes. This comprehensive review demonstrates the vital role of NLRP3 inflammasome activation in human reproductive diseases together with the underlying mechanisms, offers new insights for mechanistic studies of reproduction, and provides promising possibilities for the development of drugs targeting the NLRP3 inflammasome for the treatment of reproductive disorders in the future.

Objective. To evaluate the effects of He’s Yangchao Recipe (HSYC) on ameliorating ovarian oxidative stress of aging mice under consecutive superovulation. Methods. An 8-month-old C57BL/6 female mouse was chosen to establish an aging model under ovarian hyperstimulation. Mice were randomly separated into four groups: R1 as the control group, R4 as the model group, NR4 with N-acetyl-L-cysteine (NAC) administration, and TR4 with HSYC administration. Oocyte collection, in vitro fertilization, and embryo culture were performed. The serum hormone levels were measured by enzyme-linked immunosorbent assays (ELISA); the reactive oxygen species (ROS) level of oocytes, the number of growing follicles, corpus luteum, ovulated oocytes, and developing embryos at each stage, along with the proportions of fragmented oocytes and abnormal mitochondria in granulosa cells (GCs) and the apoptosis rate of GCs were calculated; the mRNA and protein levels of JNK, P53, BAX were detected by real-time PCR and the Simple Western System. Results. HSYC enhanced estradiol, progesterone, and inhibin-B levels and increased growing follicle and corpus luteum and ovulated egg counts compared to the R4 group ( ), whereas it decreased the proportions of fragmented oocytes ( ); Meanwhile, embryos from mice subjected to four superovulation cycles with HSYC treated had a higher hatching potential. The ROS level of oocytes is downregulated by HSYC ( ) and the percentage of abnormal mitochondrial in ovaries of the TR4 group was also significantly declined compared to the R4 group ( ); the most TUNEL-positive cells proportion was detected in the R4 group; nevertheless, HSYC effectively attenuated this detrimental effect ( ). The mRNA and protein expressions of JNK and P53 in ovary tissues were reduced in the TR4 group while these genes were upregulated by repeated superovulation ( ). Conclusions. HSYC exerted promising effects on promoting the diminished ovarian reserve and decreased oocyte quality induced by both aging and consecutive ovarian superovulation, potentially via the ROS/JNK/p53 pathway.

Background: Ulcerative colitis (UC) has a complex etiology, and whether there are sex-related differences in its molecular mechanisms remains unclear. This study employed multi-omics analysis to explore sex-based differences in UC, aiming to provide support for personalized treatment.Methods: The GSE36807 and GSE206171 datasets from the GEO database were grouped by sex. Data were preprocessed using the R software, and DEGs identified using the limma package and key modules of WGCNA. LASSO regression was conducted to screen hub genes, ROC curves were used to evaluate diagnostic value, CIBERSORT was used to analyze immune cell proportions, and Spearman’s correlation was performed to explore associations. The single-cell dataset GSE214695 was processed using Seurat to analyze immune cell proportion differences. Histological, immunohistochemical, and metabolomic analyses were performed on the colon tissues of DSS-induced colitis model mice.Results: Thirty-seven DEGs and 47 co-expression modules were identified. LASSO regression highlighted RPS4Y1 as the core gene, which was significantly upregulated in males. Females showed higher proportions of resting NK cells and M0 macrophages but a lower number of eosinophils. RPS4Y1 expression was positively correlated with resting memory CD4+ T cells and eosinophils and negatively with M0 macrophages and resting mast cells. Macrophage function exhibited sex-based disparities. Increased immune cell infiltration was observed in female colon tissues compared with that in male colon tissues. Metabolomic analysis identified 140 sex-dimorphic metabolites, with significant alterations in glutathione metabolism.Conclusion: RPS4Y1 exhibits sex-specific expression in UC and plays a key role in immunomodulation. Mitochondrial energy metabolism contributes to sex-based macrophage differences, highlighting the importance of considering sex-specific mechanisms in UC diagnosis and individualized treatment.

Objective: The effect of antioxidant supplements on glucose metabolism and lipid profiles in polycystic ovary syndrome (PCOS) remains controversial. This systematic review and meta-analysis aimed to evaluate whether antioxidant supplements improve glucose metabolism and lipid profiles in women with PCOS to provide optimal nutritional supplement advice in clinical practice. Methods: The search was conducted across multiple medical databases from inception to January 1, 2022 and performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A random effects model was used to calculate the overall effects. Results: Eighteen trials (1113 participants) were included. Antioxidant supplements significantly improved insulin resistance (95% CI, −0.62, −0.30; p < 0.00001; I² =48%), fasting insulin (95% CI, −0.80, −0.44; p < 0.00001; I² = 48%), and fasting plasma glucose (95% CI, −0.54, −0.21; p < 0.00001; I² = 38%) in patients with PCOS. However, antioxidant supplements were found to not improve most indices of lipid profiles in PCOS except triglyceride. Conclusions: Antioxidant supplements are an effective intervention for relieving insulin resistance but do not significantly improve lipid metabolism in women with PCOS.

Acupuncture is an effective complementary therapy for nausea and vomiting during pregnancy (NVP). Nevertheless, the utilization of acupuncture for NVP has been minimally explored in current scholarly research, with a paucity of systematic randomized clinical trials (RCTs) in it. We aim to evaluate the effects of acupuncture on NVP after assisted reproductive techniques (ART) and explore the metabolism-related mechanism of the efficacy. This single-blind, randomized, controlled trial will randomize 68 patients with NVP after ART to a traditional acupuncture (tACP) or a sham acupuncture (sACP) group. The tACP group will receive tACP thrice a week for 2 weeks with a day interval between sessions, while the sACP group will undergo the same number of nonpenetrative acupuncture at non-acupoints for the same period. Pregnancy-specific quantification of emesis will be used to evaluate symptom severity. Routine blood and urine tests, liver and kidney function tests, human chorionic gonadotropin, nuchal translucency thickness, and embryonic development measured using ultrasound will be used to evaluate safety during pregnancy. Non-targeted metabolomic analysis will be performed to explore the association between metabolic changes and clinical symptoms. This study will elucidate the effects and safety of acupuncture in treating NVP in women undergoing ART. The results of this study will contribute to optimizing acupuncture therapies by combining the body and auricular points and exploring the underlying therapeutic mechanism using a metabolomics approach. Chinese Clinical Trial Registry, ChiCTR2300075259.

ObjectiveTo investigate the molecular mechanism by which He’s Yangchao Decoction (HSYC) improves ovarian function in a mouse model of premature ovarian insufficiency (POI).MethodsForty ICR mice were used to establish a POI model via intraperitoneal injection of cyclophosphamide and were randomly assigned to four groups: model control group, low-dose HSYC group, high-dose HSYC group, and estradiol group (positive control). Additionally, 10 age-matched ICR mice were selected as the blank control group. After intragastric intervention, the ovarian index, serum follicle-stimulating hormone (FSH) levels, and ovarian tissue expression of the FSH receptor (FSHR) were measured. A POI cell model was established by treating the human granulosa tumor cell line (KGN) with 4-hydroxycyclophosphamide. The cells were divided into four groups: solvent control group, HSYC group, inhibitor control group, and inhibitor+HSYC group, which were respectively treated with TH5487 (an OGG1 inhibitor) and HSYC-containing serum. The expressions of OGG1, mitochondrial DNA (mtDNA) oxidative damage markers, and pyroptosis-related proteins were detected by molecular docking, Western blotting, and immunofluorescence.ResultsCompared with the blank control group, the model control group showed a decreased ovarian index (P<0.05) and increased serum FSH levels (P<0.01). The ovarian index was higher in both the low- and high-dose HSYC groups compared with the model control group (both P<0.05). FSHR expression in ovarian tissue was lower in the model control group than that in the blank control group, but was higher in the high-dose HSYC group compared with the model control group (P<0.05 or P<0.01). Molecular docking confirmed strong binding affinity between the active components of HSYC and OGG1 (binding energy: －6.3 to －8.3 kcal/mol). Western blotting analysis revealed that OGG1 protein expression in the ovaries of the model control group was significantly reduced compared with the blank control group, while it was increased in the low-dose HSYC group and the estradiol group (P<0.05 or P<0.01). Immunofluorescence results demonstrated that the expression levels of mito-chondrial transcription factor A (TFAM) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) were decreased in the model control group compared with the blank control group (P<0.01), whereas their expressions were significantly elevated in the high-dose HSYC group and the estradiol group (all P<0.01). Cell experiments showed that TH5487 intervention increased the expression of 8-oxoguanine (8-OxoG) (P<0.01), while HSYC-containing serum intervention reduced 8-OxoG expression and increased TFAM expression (P<0.01). The expression of pyroptosis-related proteins (GSDMD, N-GSDMD, caspase-1, IL-1β) increased after TH5487 intervention (P<0.05), whereas HSYC-containing serum suppressed their expression (all P<0.05).ConclusionHSYC improves POI by upregulating OGG1 expression, mitigating mtDNA oxidative damage, and inhibiting granulosa cell pyroptosis.