dentification of Circular RNAs as a Novel Biomarker for Ovarian Endometriosis

Background： Endometriosis is a challenging disease with symptoms such as dysmenorrhea and infertility. However, its etiology is still vague and there is still no effective markers or treatment. This study aimed to profile the circular RNAs （circRNAs） expressed in eutopic endometrium from patients with ovarian endometriosis and explore potential clues to the pathogenesis of endometriosis, providing an evidence for clinical diagnosis and treatment. Methods： A total of 63 clinical samples, including control endometrium 01 = 22） and eutopic endoxnetrium （n = 41）, were collected from Peking Union Medical College Hospital between May 1,2016, and December 31,2016. Of them, four samples in each group were used for circRNA microarray. Then, tbur upregulated circRNAs were screened out for quantitative real-time polymerase chain reaction （qRT-PCR） validation. After that, bioinformatics analysis was pertbrmed to predict miRNAs targeted by validated circRNAs and investigate the circRNA-miRNA-mRNA interactions. Results： Among 88 differentially expressed circRNAs, 11 were upregulated and 77 were downregulated in eutopic endometrium of patients with endometriosis, qRT-PCR validation results for two upregulated circRNAs （circ0004712 and circ_O002198） matched the microarray results. The area under the receiver operating characteristic curve of circ_0002198 for distinguishing ovarian endometriosis was 0.846 （95% confidence interval [C1]： 0.752-0.939; P 〈 0.001 ） while that ofcitv_O004712 was 0.704 （95% CI： 0.571-0.837; P = 0.008）. On the basis of target prediction, we depicted the molecular interactions between the identified circRNAs and their dominant target miRNAs, as well as constructed a circRNA-miRNA-mRNA network. Conclusions： This study provides evidence that circRNAs are differentially expressed between eutopic and normal endometrium, which suggests that circRNAs are candidate factors in the activation ofendometriosis, circ_0002198 and circ0004712 may be potential novel biomarkers for the diagnosis of ovarian endometriosis.

Establishment of endometriotic models: the past and future

Endometriosis is a prevalent chronic disease that affects approximately 6%to 10%of reproductive-aged women.Although numerous researchers have endeavored to explore the etiology of endometriosis over a century,its etiology still remains an enigma.The exploration of pathophysiologic mechanism and novel therapy for endometriosis depends on ideal endometriotic models.In the previous decade,various endometriotic models have been established;therefore,we made a conclusion for available information on these models.This review summarized the common experimental models used in endometriotic studies,including their origins,characteristics,applications,and limitations.Endometriotic models played an important role in studying etiologies and novel treatments of endometriosis during the last decades.Among them,animal models and endometriotic cell lines were viewed as most common studying tools to explore the intrinsic entities of endometriosis.In addition,endometrial organoid also emerged and was regarded as an ideal studying tool for endometriosis research.Different research models collectively complement each other to advance the endometriosis research.The successful establishment of endometrial organoids means that organoids are expected to become an ideal model for studying endometriosis in the future.