Endometriosis (EMs) occurs in approximately 50% of women with infertility. The main causes of EMs-related infertility are follicle dysplasia and reduced oocyte quality. Iron overload occurs in ovarian follicular fluid (FF) of patients with EMs, and this condition is associated with oocyte maturation disorder. However, the underlying molecular mechanism remains largely unknown. In the present study, we identified the mechanism underlying ferroptosis in ovarian granulosa cells and oocyte maturation failure in EMs based on a retrospective review of in vitro fertilization/intracytoplasmic sperm injection-frozen embryo transfer outcomes in infertile patients with EMs. Mouse granulosa cells were treated with EMs-related infertile patients' follicular fluid (EMFF) in vitro. Western blot analysis, quantitative polymerase chain reaction, fluorescence staining, and transmission electron microscopy were used to assess granulosa cells ferroptosis. The effects of exosomes were examined by nanoparticle tracking analysis, RNA-seq, and Western blot analysis. Finally, the therapeutic values of vitamin E and iron chelator (deferoxamine mesylate) in vivo were evaluated in an EMs-related infertility model. Patients with ovarian EMs experienced poorer oocyte fertility than patients with non-ovarian EMs. We observed that EMFF with iron overload-induced granulosa cell ferroptosis in vitro and in vivo. Mechanically, nuclear receptor coactivator four-dependent ferritinophagy was involved in this process. Notably, granulosa cells undergoing ferroptosis further suppressed oocyte maturation by releasing exosomes from granulosa cells. In therapeutic studies, vitamin E and iron chelators effectively alleviated EMs-related infertility models. Our study indicates a novel mechanism through which EMFF with iron overload induces ferroptosis of granulosa cells and oocyte dysmaturity in EMs-related infertility, providing a potential therapeutic strategy for EMs-related infertility.

Problem: Endometriosis (EMS) is a chronic inflammatory disease with unclear pathogenesis. Three studies have uncovered the influence of gut microbiota on mice with EMS, but no study has investigated the characteristics of fecal metabolomics to determine some important clues on EMS. This research aims to uncover the interaction between fecal metabolomics and gut microbiota in EMS mice. Method of study: Female C57BL/6J mice were used to construct the EMS model. Non-target metabolomics was applied to detect the fecal metabolites of EMS mice. The 16s rRNA sequencing was used for clarifying the composition of the gut microbiota. The functional characteristics of gut microbiota were analyzed using the PICRUSt. The receiver operator characteristic curve (ROC) analysis was utilized for determining the potential important differential metabolites, and the Spearman correlation coefficient was applied for expressing the correlation between the important differential metabolites and gut microbiota. Results: A total of 156 named differential metabolites were screened. The diversity and the abundance of gut microbiota in EMS mice decreased. Eleven pathways were involved in the differential metabolites and the functional prediction of gut microbiota, among which the second bile acid biosynthesis and alpha-linolenic acid (ALA) metabolism were the significant enrichment pathways. The increased abundance of chenodeoxycholic and ursodeoxycholic acids and the decreased abundance of ALA and 12,13-EOTrE were found in the feces of EMS mice. Conclusion: The abnormal fecal metabolites, which are influenced by dysbacteriosis, may be the characteristics of EMS mice and can be the potential important indices to distinguish the disease.

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Taken together, the present studies demonstrate that pan-LXR activation increases hepatic fatty acid desaturation via the induction of SCD1 expression in an LXRα-dependent and SREBP1c-mediated manner.

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Problem This study aims to investigate the effects of alpha‐linolenic acid (ALA) on the gut microbiota (GM) and the abdominal environment in mice with endometriosis (EMS). Methods The effects of faecal microbiota transplantation (FMT) from EMS mice on mice treated with antibiotic cocktail were conducted. The 16S rRNA sequencing and PICRUSt software were used to detect the structure and function of GM respectively. The protein levels of Claudin 4 and ZO‐2 in the intestinal wall were detected using the western blotting. The level of LPS in the abdominal cavity was detected using enzyme‐linked immunosorbent assay (ELISA). The content of macrophages in the abdominal cavity was detected using flow cytometry. Results The exogenous supplementation of ALA could restore the abundance of Firmicutes and Bacteroidota in EMS mice. After the ALA treatment, the abundance of 125 functional pathways and 50 abnormal enzymes related to GM in EMS mice was significantly improved (p < .05). The expression of the ZO‐2 protein in the intestinal wall was decreased, and the level of LPS in the abdominal cavity was significantly increased after FMT from EMS mice (p < .05). ALA could increase the expression of the ZO‐2 protein in the intestinal wall of EMS mice, reduce the level of LPS in the abdominal cavity (p < .05) and reduce the aggregation of peritoneal macrophages (p < .05). Conclusion Alpha‐linolenic acid can improve the GM, intestinal wall barrier and abdominal inflammatory environment and reduce the level of LPS in mice with EMS.

ObjectivesTo determine the therapeutic effect of a Mediterranean diet (MED) combined with a low-carbohydrate (LC) dietary model in overweight polycystic ovary syndrome (PCOS) patients.MethodsIn this 12-week randomized controlled clinical trial, 72 overweight patients with PCOS were randomly assigned to one of two energy-restricted dietary models: the MED/LC diet or the Low fat (LF) diet. After the intervention, the number of the two groups returned to normal menstruation was counted. Body weight, body mass index (BMI), waist circumference, waist-hip ratio (WHR), body fat percentage (BF%), serum fasting insulin(FINS), fasting plasma glucose(FPG), insulin resistance index (HOMA-IR), quantitative insulin sensitivity index (QUIKI), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), total testosterone (TT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) were compared between 2 groups before and after intervention.ResultsMED/LC group had more significant reduction trend in weight (−6.10 ± 1.52 kg vs −4.79 ± 0.97 kg, P &lt; 0.05), BMI (−2.12 ± 0.57 kg/m2 vs −1.78 ± 0.36 kg/m2, P &lt; 0.05), WC (−6.12 ± 5.95 cm vs −3.90 ± 1.58 cm, P &lt; 0.05), WHR (−0.06 ± 0.02 vs −0.03 ± 0.02, P &lt; 0.05), BF% (−2.97% ± 1.78% vs −1.19% ± 0.91%, P &lt; 0.05), TT (−0.20 ± 0.24 ng/mL vs 0.08 ± 0.11 ng/Ml, P &lt; 0.001), LH (−5.28 ± 3.31 mIU/mL vs −3.39 ± 3.64 mIU/mL, P &lt; 0.05), and LH/FSH (−1.18 ± 0.75 vs -0.66 ± 1.05, P &lt; 0.05) compared with the LF group. In addition, FPG (0.05 ± 0.38 mmol/mL vs -0.50 ± 1.01 mmol/mL, P &lt; 0.001), FINS (−4.88 ± 6.11 μU/mL vs −8.53 ± 5.61 μU/mL, P &lt; 0.01), HOMA-IR index (−1.11 ± 1.51 vs −2.23 ± 0.25, P &lt; 0.05), and QUIKI index (0.014 ± 0.016 vs 0.028 ± 0.019, P &lt; 0.05) decreased significantly in the MED/LC group compared with the LF group. Comparing the changes in lipid parameters between the two groups (LF vs MED/LC), significant differences in TG (−0.33 ± 0.32 mmol vs −0.76 ± 0.97 mmol, P &lt; 0.05), TC (−0.40 ± 1.00 mmol vs −1.45 ± 2.00 mmol, P &lt; 0.05), and LDL-C (−0.41 ± 1.05 mmol vs −0.73 ± 0.76 mmol, P &lt; 0.05) were observed.ConclusionThe results of this study suggest that the MED/LC diet model is a good treatment for overweight PCOS patients, significantly restoring their menstrual cycle, improving their anthropometric parameters and correcting their disturbed endocrine levels, and its overall effectiveness is significantly better than the LF diet model. Therefore, this study recommends that the MED/LC diet model can be used in the clinical treatment of patients with overweight PCOS.

Extraintestinal manifestations (EIMs) cause increased morbidity and decreased quality of life in Crohn disease (CD). Ankylosing spondylitis (AS) belongs to EIMs. Very little is known on the clinical features of CD concomitant with AS. This study is to investigate the clinical features of CD patients with AS.We retrospectively collected all CD patients with AS in our hospital, and established a comparison group (CD without AS) with age, sex, and duration of Crohn disease matched. Clinical information was retrieved for comparison.Eight CD + AS patients were identified from 195 CD patients. Sixteen CD patients were randomly selected into comparison group. All CD + AS patients were male, HLA-B27 (+), and rheumatoid factor (−) with an average age of 40.8 ± 4.52 years. Significant correlation between disease activity of CD and AS was revealed (r = 0.857, P = 0.011). Significant correlation between disease activity of CD and functional limitation associated with AS was identified (r = 0.881, P < 0.01). C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and globulin were positively correlated to Crohn disease activity index (CDAI), Bath AS disease activity index, and Bath AS functional index(BASFI) scores (r = 0.73–0.93, P < 0.05). Albumin was negatively associated with CDAI and BASFI (r = −0.73 to −0.91, P < 0.05). The ratio of albumin to globulin (Alb/Glo) was significantly related to all 3 scores (r = −0.81 to −0.91, P < 0.05).Male predominance with a 4.12% concomitant incidence of AS is observed in CD patients. Disease activity of CD correlates with disease activity of AS and functional limitation caused by AS. CRP, ESR, and Alb/Glo may serve as biomarkers for disease activity and functional limitation in CD patients concomitant with AS, although future studies are expected.