miR-4443 Contained Extracellular Vesicles: A Factor for Endometriosis Progression by PI3K/AKT/ACSS2 Cascade in-vitro.

Introduction: Endometriosis (EM) is an estrogen-dependent benign gynecologic disease affecting approximately 10% of reproductive-age women with a high recurrence rate, but lacks reliable biomarkers. No previous studies have investigated the possible use of extracellular vesicle (EV)-associated micro RNAs (miRNAs) from menstrual blood (MB) as candidate diagnostic or prognostic markers of EM. Methods: Specimens were obtained from endometriosis and non-endometriosis patients at the International Peace Maternity and Child Health Hospital in Shanghai. Microarray was used to screen differentially expressed miRNAs among peritoneal fluid (PF), fallopian tube fluid (FF), and MB. Dual-luciferase reporter gene assay was carried out to verify the relationship between miR-4443 and ACSS2. Cell proliferation and Transwell invasion assays were performed in vitro after intervention on miR-4443 and ACSS2 in hEM15A human endometrial stromal cells and primary human endometrial stromal cells (hESCs). Spearman correlation analysis, receiver operating characteristic (ROC) curve analysis, and survival analysis were applied to clinical data, including severity of symptoms and relapse of EM among EM patients. Results: EV-associated miR-4443 was abundant in MB of endometriosis patients. ACSS2 knockdown and miR-4443 overexpression promoted cell proliferation and migration via the PI3K/AKT pathway. miR-4443 levels in MB-EVs were positively correlated with the degree of dyspareunia (r=0.64; P<0.0001) and dysmenorrhea (r=0.42; P<0.01) in the endometriosis group. ROC curve analyses showed an area under the curve (AUC) of 0.741 (95% CI 0.624-0.858; P<0.05) for miR-4443 and an AUC of 0.929 (95% CI 0.880-0.978; P<0.05) for the combination of miR-4443 and dysmenorrhea. Conclusion: MB-derived EV-associated miR-4443 might participate in endometriosis development, thus providing a new candidate biomarker for the noninvasive prediction of endometriosis recurrence.

Trophoblastic infiltration of tubal pregnancy may have an association with chronic inflammation of the fallopian tube.

OBJECTIVE: To explore the factors associated with trophoblastic infiltration in ampullary pregnancy from the perspective of clinical and pathologic characteristics. METHODS: A single-center, retrospective, clinicopathologic cohort study was conducted in women who were diagnosed with tubal pregnancy and underwent salpingectomy in the International Peace Maternal and Child Health Care Hospital from January 2018 to June 2021. RESULTS: A total of 333 eligible women diagnosed with ampullary pregnancy were included in the analysis. Multivariate logistic analysis showed that preoperative ß-human chorionic gonadotropin greater than 3000 IU/L (adjusted odds ratio [aOR] 3.77, 95% confidence interval [CI] 2.02-7.03), and vascular remodeling phenomenon (aOR 4.34, 95% CI 2.41-7.83) were positively correlated with the infiltration of extravillous trophoblasts into serosa, while presence of chronic inflammation of the fallopian tube was a negatively corellated factor (aOR 0.49, 95% CI 0.29-0.85). CONCLUSION: The depth of trophoblastic infiltration in tubal pregnancy may be related to the presence of chronic inflammation in the fallopian tube. A tubal pregnancy in a tube with chronic salpingitis is more likely to develop into an abortive ectopic pregnancy; whereas in a fallopian tube without chronic inflammation, the risk of it developing into a ruptured ectopic pregnancy increases. Hence, early identification is needed to properly address this dangerous pregnancy situation.