Gut Microbiota Exceeds Cervical Microbiota for Early Diagnosis of Endometriosis.

The diagnosis of endometriosis is typically delayed by years for the unexclusive symptom and the traumatic diagnostic method. Several studies have demonstrated that gut microbiota and cervical mucus potentially can be used as auxiliary diagnostic biomarkers. However, none of the previous studies has compared the robustness of endometriosis classifiers based on microbiota of different body sites or demonstrated the correlation among microbiota of gut, cervical mucus, and peritoneal fluid of endometriosis, searching for alternative diagnostic approaches. Herein, we enrolled 41 women (control, n = 20; endometriosis, n = 21) and collected 122 well-matched samples, derived from feces, cervical mucus, and peritoneal fluid, to explore the nature of microbiome of endometriosis patients. Our results indicated that microbial composition is remarkably distinguished between three body sites, with 19 overlapped taxa. Moreover, endometriosis patients harbor distinct microbial communities versus control group especially in feces and peritoneal fluid, with increased abundance of pathogens in peritoneal fluid and depletion of protective microbes in feces. Particularly, genera of Ruminococcus and Pseudomonas were identified as potential biomarkers in gut and peritoneal fluid, respectively. Furthermore, novel endometriosis classifiers were constructed based on taxa selected by a robust machine learning method. These results demonstrated that gut microbiota exceeds cervical microbiota in diagnosing endometriosis. Collectively, this study reveals important insights into the microbial profiling in different body sites of endometriosis, which warrant future exploration into the role of microbiota in endometriosis and highlighted values on gut microbiota in early diagnosis of endometriosis.

Association of three missense mutations in the homocysteine-related MTHFR and MTRR gene with risk of polycystic ovary syndrome in Southern Chinese women.

BACKGROUND: The etiology between homocysteine and polycystic ovary syndrome (PCOS) is unclear. In humans, the level of homocysteine is mainly affected by two enzymes: methylene tetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR). While the activity of these two enzymes is mainly affected by three missense mutations, namely C677T (MTHFR), A1298C (MTHFR), and A66G (MTRR). This study aims to examine the association between the three missense mutations and PCOS and investigate whether the three missense mutations exerted their effect on PCOS by affecting the homocysteine level. METHODS: A case-control study was designed, comprising 150 people with PCOS and 300 controls. Logistic regression analysis was used to assess the association between the three missense mutations and PCOS. Linear regression analysis was used to assess the association between the three missense mutations and the homocysteine level. Mediation analysis was used to investigate whether the three missense mutations exerted their effect on PCOS by affecting the homocysteine level. RESULTS: Following adjustments and multiple rounds of testing, MTHFR A1298C was found to be significantly associated with PCOS in a dose-dependent manner (compared to AA, OR = 2.142 for AC & OR = 3.755 for CC; P < 0.001). MTRR A66G was nominally associated with PCOS. Mutations in MTHFR A1298C and MTRR A66G were significantly associated with the homocysteine level. Mediation analysis suggested the effect of MTHFR A1298C on PCOS was mediated by homocysteine. CONCLUSIONS: MTHFR A1298C and MTRR A66G were associated with PCOS, and MTHFR A1298C might affect the risk of PCOS by influencing the homocysteine level.

Correction to: miR-205-5p inhibits human endometriosis progression by targeting ANGPT2 in endometrial stromal cells.

An amendment to this paper has been published and can be accessed via the original article.

miR-205-5p inhibits human endometriosis progression by targeting ANGPT2 in endometrial stromal cells.

BACKGROUND: miRNA expression profiles in ectopic endometrium (EC) serving as pathophysiologic genetic fingerprints contribute to determining endometriosis progression; however, the underlying molecular mechanisms remain unknown. METHODS: miRNA microarray analysis was used to determine the expression profiling of EC fresh tissues. qRT-PCR was performed to screen miR-205-5p expression in EC tissues. The roles of miR-205-5p and its candidate target gene, angiopoietin-2 (ANGPT2), in endometriosis progression were confirmed on the basis of both in vitro and in vivo systems. miR-205-5p and ANGPT2 expression were measured by in situ hybridization and immunochemistry, and their clinical significance was statistically analysed. RESULTS: miR-205-5p was screened as a novel suppressor of endometriosis through primary ectopic endometrial stromal cell migration, invasion, and apoptosis assay in vitro, along with endometrial-like xenograft growth and apoptosis in vivo. In addition, ANGPT2 was identified as a direct target of miR-205-5p through bioinformatic target prediction and luciferase reporter assay. Re-expression and knockdown of ANGPT2 could respectively rescue and simulate the effects induced by miR-205-5p. Importantly, the miR-205-5p-ANGPT2 axis was found to activate the ERK/AKT pathway in endometriosis. Finally, miR-205-5p and ANGPT2 expression were closely correlated with the endometriosis severity. CONCLUSION: The newly identified miR-205-5p-ANGPT2-AKT/ERK axis illustrates the molecular mechanism of endometriosis progression and may represent a novel diagnostic biomarker and therapeutic target for disease treatment.