Endometriosis occurs when endometrial tissue exists outside the uterine cavity. The presence of ectopic endometrial tissue and resultant inflammation cause serious symptoms, including chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility. Pelvic inflammatory disease is caused by the ascension of pathogenic bacteria from the vagina to the uterus, Fallopian tubes, and ovaries. The factors involved in the pathogenesis of the two conditions are not clearly understood, but recent studies have suggested that disturbances of the female reproductive tract microbiota and inflammatory processes influence the development of both diseases. Using data from the National Health Insurance Research Database (NHIRD), we conducted a study to assess the association of pelvic inflammatory disease (PID) with endometriosis. An age-matched control group including patients without PID was selected. Patients with a pre-existing diagnosis of endometriosis were excluded. This nationwide retrospective cohort study, involving a total of 141,460 patients, demonstrated that patients with PID had a three-fold increase in the risk of developing endometriosis (HR = 3.02, 95% CI = 2.85–3.2).

Background: Air pollutants cause endocrine disorders and hormone disruption. The relationship between air pollutants and polycystic ovary syndrome (PCOS) must be carefully investigated using a nationwide cohort. Methods: Data were extracted from two nationwide databases, namely Longitudinal Health Insurance Database and Taiwan Air Quality Monitoring Database, and analyzed. The study considered a range of data that began on 1 January 2000 and ended on 31 December 2013. Women diagnosed with PCOS were excluded. From the residential data, the study assessed the daily concentrations of sulfur dioxide (SO₂), nitrogen oxides (NOx), nitrogen monoxide (NO), nitrogen dioxide (NO₂), and PM_2.5 the women were exposed to. A Cox proportional hazard regression model was applied to assess PCOS risk. Results: In total, 91,803 women were enrolled in this study; of those women, 2072 developed PCOS after 12 years of follow-up. The mean daily concentrations of SO₂, NOx, NO, NO₂, and PM_2.5 women were exposed to were 4.25 (±1.44) ppb, 20.41 (±6.65) ppb, 9.25 (±4.36) ppb, 20.99 (±3.33) ppb, and 30.85 (±6.16) μg/m³, respectively. Compared with the first-quartile levels of exposure, the fourth-quartile levels of exposure to SO₂, NOx, NO, NO₂, and PM_2.5 increased PCOS risk by 10.31 times (95% CI = 8.35–12.7), 3.37 times (95% CI = 2.86–3.96), 4.18 times (95% CI = 3.57–4.89), 7.46 times (95% CI = 6.38–8.71), and 3.56 times (95% CI = 3.05–4.15), respectively. Conclusion: Women exposed to a high concentrations of air pollutants, namely SO₂, NO, NO₂, NOx, and PM_2.5, had a high PCOS risk.

Background: Mucin 4 (MUC4) plays an important role in protecting and lubricating the epithelial surface of reproductive tracts, but its role in the pathogenesis of endometriosis is largely unknown. Methods: To correlate MUC4 polymorphism with the risk of endometriosis and endometriosis-related infertility, we performed a case-control study of 140 patients and 150 healthy women. Six unique single-nucleotide polymorphisms (SNPs) (rs882605, rs1104760, rs2688513, rs2246901, rs2258447 and rs2291652) were selected for this study. DNA fragments containing the target SNP sites were amplified by polymerase chain reaction using the TaqMan SNP Genotyping Assay System to evaluate allele frequency and distribution of genotype in MUC4 polymorphisms. Results: Both the T/G genotype of rs882605 and the frequency of haplotype T-T (rs882605 and rs1104760) were higher in patients than in controls and were statistically significant. The frequency of the C allele at rs1104760, the C allele at rs2688513, the G allele at rs2246901 and the A allele at rs2258447 were associated with advanced stage of endometriosis. Moreover, the G allele at rs882605 was verified as a key genetic factor for infertility in patients. Protein sequence analysis indicated that amino acid substitutions by genetic variations at rs882605, rs2688513 and rs2246901 occur in the putative functional loops and the type D von Willebrand factor (VWFD) domain in the MUC4 sequence. Conclusions: MUC4 polymorphisms are associated with endometriosis development and endometriosis-related infertility in the Taiwanese population.

Introduction: Resistance of cancer stem/progenitor cells (CSPCs) to chemotherapy can lead to cancer relapse. Ovarian teratocarcinoma (OVTC) arises from germ cells and comprises pluripotent cells that can be used to study cancer cell stemness. In this study, we evaluated whether microRNA-21 (miR-21) promotes ovarian teratocarcinoma by maintaining cancer stem/progenitor populations. Methods: The lentiviral delivery system was used to upregulate or to suppress the expression of miR-21 in the human ovarian teratocarcinoma cell line PA1 and cell growth assays were used to monitor the expression of miR-21 at different time points. Antibodies directed toward CD133, a stem cell marker, were used to identify CSPCs in the PA1 cell population, and the level of miR-21 expression was determined in enriched CSPCs. Stem cell functional assays (sphere assay and assays for CD133 expression) were used to assess the effects of miR-21 on progression of the CD133+ population. Results: Knockdown of miR-21 in PA1 cells attenuated growth of PA1 cells whereas overexpression of miR-21 promoted cell growth. Moreover, knockdown of miR-21 resulted in a marked reduction in the CD133+ population and sphere formation of CSPCs. In contrast, overexpression of miR-21 resulted in a marked increase in the population of CD133+ cells as well as sphere formation of CSPCs. Conclusions: MicroRNA-21 plays a significant role in cancer growth by regulating stemness in cancer cells.

Genetic alterations of mucin genes, such as MUC2 and MUC4, were previously identified to be associated with endometriosis and related infertility. Additionally, gene expression profiling has confirmed MUC17 to be overexpressed in mucinous ovarian carcinoma; however, its associated risk for endometriosis remains unclear. This study was focused on the potential impact of genetic variations in MUC17 on endometriosis development and associated clinical features. The study subjects included 189 female Taiwanese patients with pathology-proven endometriosis and 191 healthy Taiwanese women as controls. Five single-nucleotide polymorphisms (rs4729645, rs10953316, rs74974199, rs4729655, and rs4729656) within the MUC17 gene were selected and genotyped using the Taqman genotyping assay to examine the allele frequency and genotype distributions of MUC17 polymorphisms. Genotyping revealed that the A allele at rs10953316 in MUC17 was a protective genetic factor in endometriosis development (p = 0.008; OR = 0.53; 95 % CI: 0.36-0.79). Genetic variation of rs4729655 protected patients against endometriosis-induced infertility, but was associated with a higher cancer antigen 125 (CA125) level. Base-pairing analysis, called MaxExpect, predicted an additional loop in the mRNA structure caused by rs10953316 polymorphism, possibly influencing ribosome sliding and translation efficiency. Such predictions were confirmed by immunohistochemistry that patients with AA genotype at rs10953316 showed low MUC17 levels in their endometrium, patients with GA genotype showed moderate levels, and strong staining could be found in patients with GG genotype. MUC17 polymorphisms are involved in endometriosis development and the associated infertility in the Taiwanese population.

Background: Mucins are highly glycosylated proteins protecting and lubricating epithelial surface of respiratory, gastrointestinal and reproductive tracts. Members of the mucin protein family have been suggested to play an important role in development of endometriosis and infertility. This study investigates genetic association of mucin2 (MUC2) with the risk of endometriosis and endometriosis-related infertility.Methods: This case-control study was conducted at China Medical University Hospital, with 195 endometriosis patients and 196 healthy controls enrolled. Genotyping of six SNPs (rs2856111, rs11245936, rs10794288, rs10902088, rs7103978 and rs11245954) withinMUC2gene were performed by usingTaqmangenotyping assay; individual SNP and haplotype associations with endometriosis and endometriosis-related infertility were assessed byχ²test.Results: Endometriosis patients exhibit significantly lower frequency of the rs10794288 C allele, the rs10902088 T allele and the rs7103978 G allele (P= 0.030, 0.013 and 0.040, respectively). In addition, the rs10794288 C allele and the rs10902088 T allele were also less abundant in patients with infertility versus fertile ones (P= 0.015 and 0.024, respectively). Haplotype analysis of the endometriosis associated SNPs inMUC2also showed significantly association between the most common haplotypes and endometriosis or endometriosis-related infertility.Conclusions: MUC2polymorphisms, especially rs10794288 and rs10902088, are associated with endometriosis as well as endometriosis-related infertility. Our data present MUC2 as a new candidate involved in development of endometriosis and related infertility in Taiwanese Han women.