Endometriosis is a common, benign, and estrogen-dependent disease characterized by pelvic pain and infertility. To date, the pathogenesis of endometriosis remains unclear. Recent studies have demonstrated that noncoding RNAs, including microRNAs and long noncoding RNAs, play important roles in the development of endometriosis. Expression profiling of miRNAs in endometrial tissue was characterized using microarrays. The most differentially expressed miRNAs were confirmed using quantitative reverse transcriptase-polymerase chain reaction analysis in additional ectopic endometrial (n = 27) and normal endometrial (n = 12) tissues. For in-vitro functional studies, 5-ethynyl-2′-deoxyuridine incorporation assay, Transwell assay, and dual-luciferase reporter assay were used to measure the proliferation, migration, and luciferase activity of miR-200c and the predicted targets of miR-200c in primary endometrial stromal cells (HESCs) derived from human endometrial biopsies, respectively. For in-vivo therapeutic interventions, polymeric nanoparticles of polyethylenimine–polyethylene glycol–arginine–glycine–aspartic acid were used for delivery of miR-200c mimic and inhibitor to determine the therapeutic effect of miR-200c in a rat model of endometriosis. Exogenous overexpression of miR-200c inhibited the proliferation and migration of HESCs, which were mainly regulated by metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). In contrast, inhibition of miR-200c promoted the proliferation and migration of HESCs, while the simultaneous silencing of MALAT1 expression exerted the opposite effects. We demonstrated that expression of MALAT1 in ectopic endometrial specimens was negatively correlated with that of miR-200c and that MALAT1 knockdown increased the level of miR-200c in HESCs. Moreover, the transfection of endometrial stromal cells with the miR-200c mimic or MALAT1 siRNAs decreased the protein levels of mesenchymal markers ZEB1, ZEB2, and N-cadherin and increased the protein levels of the epithelial marker E-cadherin. Furthermore, using a rat endometriosis model, we showed that local delivery of the miR-200c mimic significantly inhibited the growth of ectopic endometriotic lesions. The MALAT1/miR-200c sponge may be a potential therapeutic target for endometriosis.

Background: Endometrial cancer is the most common gynecologic malignancy worldwide. Polymorphisms in MALAT1 have been demonstrated to play critical roles in cancer. However, the roles of MALAT1 polymorphisms in the etiology of endometrial cancer have not been well documented. Methods: We genotyped three MALAT1 polymorphisms in 249 endometrial cancer cases and 446 cancer‐free female controls using quantitative polymerase chain reaction with TaqMan probes. To estimate the association between MALAT1 polymorphisms (rs591291 C>T, rs664589 C>G, and rs4102217 G>C) and the risk of endometrial cancer, an unconditional logistic regression model was conducted to calculate the odds ratio (OR) and the 95% confidence interval (CI), adjusting for surgery history, menopause, number of deliveries, BMI, and FIGO stage. Results: We found that the MALAT1 rs664589 C>G polymorphism was significantly associated with endometrial cancer risk (heterogeneous: adjusted OR = 0.57, 95% CI = 0.34‐0.93, P = .026; homogenous: adjusted OR = 3.74, 95% CI = 1.12‐12.45, P = .032; and recessive: adjusted OR = 4.06, 95% CI = 1.22‐13.48, P = .022). Stratified analysis further demonstrated that the MALAT1 rs664589 C>G polymorphism significantly increased the risk of endometrial cancer susceptibility in patients with no history of surgery, more deliveries, BMI between 25 and 29.9, and FIGO stages II‐III. Compared with the wild‐type GCG haplotype carriers, individuals with CGG haplotypes had a higher risk of developing endometrial cancer. Conclusion: The MALAT1 rs664589 C>G polymorphism was associated with a significant increase in endometrial cancer risk.

Background: The use of visceral obesity as an indicator for predicting female infertility risk has not been well established. The body roundness index (BRI) is a novel, non-invasive indicator of visceral fat; however, previous reports have not addressed the relationship between the BRI and female infertility. This study sought to fill this research gap by investigating the association between the BRI and the risk of female infertility.Methods: This cross-sectional study examined 3,528 women aged 18 to 45 who participated in the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2018. Infertility was defined based on responses to the reproductive health questionnaire. The BRI was calculated using waist circumference and height. Covariates included demographic traits, physical exam results, laboratory test findings, and survey data. Weighted multivariable logistic regression models and spline smoothing analysis assessed the relationship between the BRI and infertility. Bayesian statistics were used to examine the robustness of significant associations.Results: Based on their self-report data, 407 (11.54%) participants were classified as having infertility. A significantly higher percentage of participants with a higher BRI were found to have infertility. Multivariable logistic regression revealed that the BRI was significantly associated with increased female infertility risk, regardless of independent variable analysis by continuous variable or quartile (Q1 to Q4) in the fully adjusted model (Model 3, continuous variable: OR = 1.1, 95% confidence interval [CI] = 1.05–1.16, p = 0.0009; Q4 vs. Q1: OR = 2.16, 95% CI = 1.38–3.39, p = 0.0035, P_trend = 0.004). Non-linear and threshold effects in the relationship between the BRI and female infertility were identified, with an inflection point of 6.36. Subgroup analyses showed that this positive association remained consistent across most demographic and health-related categories. The Bayesian statistics analyses further confirmed the robustness of these findings.Conclusion: A positive non-linear relationship exists between the BRI and the risk of female infertility, suggesting that the BRI could serve as a valuable indicator in female fertility assessments.

Background: Obesity and metabolic syndrome are significant contributors to infertility in women and are closely associated with insulin resistance (IR). The metabolic score for insulin resistance (METS-IR) is a new, non-insulin-based fasting index used to measure IR. However, the potential of METS-IR as a predictive indicator of female infertility risk has not been established. This study aimed to explore the association between METS-IR and the risk of female infertility.Methods: This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2018. We conducted multivariate logistic regression, restricted cubic spline (RCS), and threshold effect analyses to investigate the relationship between METS-IR and female infertility.Results: According to the self-reported data, 188 (12.20%) participants were classified as infertile. A significantly higher proportion of participants with elevated METS-IR were found to have infertility. Multivariable logistic regression analysis revealed that METS-IR was significantly associated with increased risk of female infertility, irrespective of the independent variable analysis by continuous variables or tertiles in the fully adjusted model (Model 3, continuous variable: OR = 1.02, 95% confidence interval (CI):1.01–1.04, p = 0.005; tertile 3 vs. tertile 1: OR = 2.00, 95% CI = 1.21–3.28, p = 0.0128, p for trend =0.0126). RCS analysis indicated a linear correlation between METS-IR and the risk of infertility (p = 0.121), and threshold effect analysis further supported this linear association (p = 0.136). Moreover, above the inflection point of 32.94, the risk of infertility significantly increased with increasing METS-IR level (p < 0.0001).Conclusion: Our results suggest that high levels of the METS-IR index are positively associated with infertility among reproductive-aged females in the United States.

Background: Infertility poses a substantial societal and economic burden; however, current preventive strategies are limited. Recently, the relationship between gut microbiota and infertility has garnered increasing attention. The dietary index for gut microbiota (DI-GM) is a new index that reflects the diversity of the gut microbiota. However, its association with female infertility remains unclear.Methods: This cross-sectional study included 3,053 women aged 18–45 years from the National Health and Nutrition Examination Survey (NHANES) database between 2013 and 2018. Infertility was defined based on responses to a questionnaire on reproductive health. The DI-GM score was calculated by averaging the intake from two 24-h dietary recall interviews. Weighted multivariable logistic regression, restricted cubic splines (RCS), and subgroup analyses were used to investigate the association between DI-GM and female infertility.Results: Based on self-reported data, 370 participants (12.12%) were classified as infertile. A higher proportion of participants with lower DI-GM scores experienced infertility. Multivariable logistic regression analysis indicated a negative association between DI-GM and the risk of female infertility, regardless of whether the independent variable was analyzed as a continuous variable or in quartiles in the fully adjusted model (Model 3, continuous variable: OR = 0.89, 95% confidence interval (CI): 0.80–0.98, p = 0.025; Q4 vs. Q1: OR = 0.63, 95% CI = 0.42–0.94, p = 0.032, p for trend = 0.013). The RCS curves demonstrated a non-linear relationship between the DI-GM scores and infertility risk. Subsequent subgroup analyses corroborated the robustness of these findings.Conclusion: These findings suggest a non-linear relationship between DI-GM and the risk of infertility in females, with lower DI-GM scores associated with a higher risk of infertility.