Polychlorinated biphenyls and the risk of endometriosis: Systematic review and meta-analysis.

OBJECTIVE: We aimed to collect recent findings for a deeper understanding of the association between human exposure to polychlorinated biphenyls (PCBs) and endometriosis development. METHODS: Web of Science, PubMed, Scopus, Google Scholar, and Embase were searched based on inclusion criteria from 2000 to the end of 2020. No filter was exerted to limit the language of publications and geographical restriction. Odds ratios (OR) using the random-effects model and the corresponding 95% confidence interval (CI) were calculated for each included study. RESULTS: Fourteen studies were included in our analyses. The pooled OR and 95% CI for PCB was 1.96 (1.31 to 2.93). Despite being statistically significant, there was evidence of moderate heterogeneity (I2 = 63%, P = 0.001, τ2 = 0.32). Findings from our subgroup analyses showed a significant association between PCB exposure and endometriosis among European population (OR = 3.66, 95% CI: 2.08-6.44). Also a positive association was detected between PCB exposure and an increased odds of endometriosis in studies with laparoscopy (OR = 2.32, 95% CI: 1.16-4.63) or surgery confirm of controls (OR = 1.39, 95% CI: 1.02-1.89). Moreover, according to matched-pairs design, a significant association between PCB exposure and endometriosis development was detected (OR = 1.51, 95% CI: 1.04-2.18), also heterogeneity decreased in studies with matched-pairs design (I2 = 30.4%). CONCLUSIONS: Findings of this study confirm an association between endometriosis and exposure to PCB. However, more primary studies using proper methodology are needed to confirm this association.

Serum dipeptidyl peptidase-4 activity and progranulin level in polycystic ovary syndrome patients.

BACKGROUND: Evidence showed that abnormal alteration of adipokines level may perform a key role in polycystic ovary syndrome (PCOS) pathogenesis. Dipeptidyl peptidase-4 (DPP4) and progranulin (PGRN) are two novel adipokines related to insulin resistance (IR). Thus, we aimed to determine the serum DPP4 activity and PGRN level in PCOS patients with and without IR, and non-PCOS women. METHODS: Ninety women were recruited in the present study including 60 PCOS patients (divided into two groups of 30 IR and 30 non-IR) and 30 non-PCOS women. Serum levels of insulin, fasting blood glucose, PGRN, and DPP4 activity were measured, and IR indices were calculated. RESULTS: DPP4 activity was significantly higher in PCOS-IR and PCOS-NIR patients than non-PCOS women (p<0.001, P=0.011, respectively), whereas no significant variation was detected between two groups of PCOS subjects. There was no significant difference in the level of PGRN in the three groups of the present study. CONCLUSION: The present study suggests that increasing DPP4 activity may be associated with PCOS.

Resistin and chemerin levels in follicular fluid of infertile women with endometriosis undergoing ICSI.

Chemerin and resistin are two adipocytokines involved in inflammatory processes that may paly a role in the development of endometriosis. The purpose of the current study was to examine the levels of chemerin and resistin in the follicular fluid (FF) of endometriosis patients and additionally, assess the association of FF chemerin and resistin with the severity of endometriosis and the number of mature oocyte and embryos. A total of 80 reproductive-aged women who underwent intracytoplasmic sperm injection and embryo transfer were evaluated in this study. FF samples were obtained from subjects with (n = 40) and without endometriosis (n = 40). The concentrations of chemerin and resistin were examined using ELISA. The Resistin FF level was significantly (p-value=.03) higher in women with endometriosis than women without endometriosis, while the effect size was medium (d = 0.47). There was no significant difference in Chemerin concentration between the two groups of this study. Results also showed a tendency towards the increase of FF values of resistin and chemerin in endometriosis patients with stage III-IV than stage I-II; however, this difference was not significant. No significant correlations were found between FF levels of resistin and chemerin with the number of mature oocyte and embryos. Thus, elevated FF resistin levels may be associated with endometriosis.IMPACT STATEMENTWhat is already known on this subject? To our knowledge, no studies have investigated chemerin levels in follicular fluid of infertile women with endometriosis undergoing ICSI. Although follicular fluid levels of resistin have been previously studied in endometriosis, it has not been studied yet whether its level is associated with the number of oocyte and embryos.What do the results of this study add? Our results indicate that significantly increased resistin levels in follicular fluid may be associated with the presence of endometriosis.What are the implications of these findings for clinical practice and/or further research? The findings are promising in that significantly increased resistin levels may add to the knowledge of the pathophysiology of endometriosis.

Human Exposure to Polychlorinated Biphenyls (PCBs) and The Risk of Endometriosis: A Systematic Review and Meta-Analysis Protocol.

Endometriosis is one of the gynecological disorders and its prevalence is estimated to 8.10% of reproductive-age women. In Iran, the frequency of endometriosis was reported at 29% among infertile women. The etiology of endometriosis is still unclear. Numerous environmental contaminants such as polychlorinated biphenyls (PCBs) may play important roles in endometriosis development and etiology. Iranian population has relatively low levels of PCBs. However, no studies have evaluated PCBs levels in Iranian endometriosis patients so far. At present, there is no systematic review of the relationship between only PCBs exposure and the risk of endometriosis. The aim of this systematic review and meta-analysis protocol will be to evaluate the association between only PCBs exposure and the risk of endometriosis. PubMed/MEDLINE, Web of Science, Scopus, Google Scholar, Embase, key journals, conferences/congress research papers, and the references of included primary studies will be searched. Observational studies (cross-sectional, case-control, and cohort) in humans that investigated the association between PCBs exposure and the risk of endometriosis will be included. The outcome will be endometriosis risk in association with PCBs exposure. The primary screening and data extraction will be performed by three team members independently and will be judged by opinion with the fourth member. The modified Newcastle-Ottawa Scale (NOS) will be used for the quality assessment of studies. Findings from this study will recognize the association between PCBs exposure and the risk of endometriosis. Results may provide a new window for identifying the role of PCBs as environmental risk factors in relation to the development of endometriosis. Registration number: PROSPERO; CRD42019120539.

Long noncoding RNAs as a piece of polycystic ovary syndrome puzzle.

Polycystic ovary syndrome (PCOS) is an endocrine disorder and affects 5-10% of reproductive-age women. Chronic anovulation, polycystic ovaries, and hyperandrogenism are the important features of this syndrome. Furthermore, hyperinsulinemia and central obesity are frequent in PCOS women. In recent years, noncoding RNAs detection provided new ideas to explain the etiology of female reproductive disorders. Long noncoding RNAs (lncRNAs) as a subset of noncoding RNAs are associated with the pathogenesis of manifold reproductive-related disorders. Various investigations emphasized the potential involvement of lncRNAs in PCOS development. Therefore, in this paper, we will summarize the function of numerous lncRNAs in the apoptosis and proliferation of granulosa cells (GCs), insulin resistance (IR), and steroidogenesis in PCOS.

NORAD, a critical long non-coding RNA in human cancers.

The incidence of cancer is growing worldwide, and it is becoming the most common cause of death. Long non-coding RNAs (lncRNAs) are a group of RNA transcripts with a length larger than 200 nucleotides that cannot encode proteins or peptides. LncRNAs regulate different biological functions by controlling gene expressions at transcriptional, translational, and post-translational levels. Non-coding RNA activated by DNA damage (NORAD) is a highly conserved lncRNA necessary for genome stability. LncRNA NORAD is dysregulated in various types of cancers. This biomarker has been involved in numerous processes associated with carcinogeneses, such as cell proliferation, apoptosis, invasion, and metastasis. In this paper, we reviewed the role of lncRNA NORAD and its biological functions in various human cancers to provide future research insights.

Critical roles of long noncoding RNAs in breast cancer.

Breast cancer is a major clinical challenge that affects a wide range of the female population and heavily burdens the health system. In the past few decades, attempts have been made to understand the etiology of breast cancer, possible environmental risk factors, and the genetic predispositions, pathogenesis, and molecular aberrations involved in the process. Studies have shown that breast cancer is a heterogeneous entity; each subtype has its specific set of aberrations in different cell signaling pathways, such as Notch, Wnt/ß-catenin, transforming growth factor-ß, and mitogen-activated protein kinase pathways. One novel group of molecules that have been shown to be inducted in the regulation of multiple cell signaling pathways is the long noncoding RNAs (lncRNAs). These molecules have important implications in the regulation of multiple signaling pathways by interacting with various genes, affecting the transcription process, and finally, playing roles in posttranslational control of these genes. There is growing evidence that lncRNAs are involved in the process of breast cancer formation by effecting the aforementioned signaling pathways, and that this involvement can have significant diagnostic and prognostic values in clinical contexts. The present review aims to elicit the significance of lncRNAs in the regulation of cell signaling pathways, and the resulting changes in cell survival, proliferation, and invasion, which are the hallmarks of breast cancer.

MicroRNAs in breast cancer: Roles, functions, and mechanism of actions.

Breast cancer is one of the most lethal malignancies in women in the world. Various factors are involved in the development and promotion of the malignancy; most of them involve changes in the expression of certain genes, such as microRNAs (miRNAs). MiRNAs can regulate signaling pathways negatively or positively, thereby affecting tumorigenesis and various aspects of cancer progression, particularly breast cancer. Besides, accumulating data demonstrated that miRNAs are a novel tool for prognosis and diagnosis of breast cancer patients. Herein, we will review the roles of these RNA molecules in several important signaling pathways, such as transforming growth factor, Wnt, Notch, nuclear factor-κ B, phosphoinositide-3-kinase/Akt, and extracellular-signal-regulated kinase/mitogen activated protein kinase signaling pathways in breast cancer.

The interplay of Klotho with signaling pathway and microRNAs in cancers.

Klotho (KL) gene has been accepted as an "aging suppressor" gene that encodes a single transmembrane protein in human known as Klotho which is commonly expressed in renal tubes. The interruption in the secretion of Klotho protein expedites aging whereas its high expression extends lifespan. The family of Klotho proteins has been reported to act as distinct receptors for endocrine fibroblast growth factors (FGFs), which manage multifarious metabolic processes. Further, the secreted Klotho is a hormonal factor that takes part in the ion channel organization. Numerous studies determined that this protein affects the function of a number of important signaling pathways, which may present an impact in tumorigenesis via the coordination of receptors located on them. This review article focuses on the effects of microRNAs on the performance of Klotho and how the interplay between Klotho and certain pathways like insulin-like growth factor, FGF, Wnt, and transforming growth factor ß contribute to the biogenesis of cancer. The present study is also pointed at defining the molecular mechanisms of these interactions.

The crosstalk between trace elements with DNA damage response, repair, and oxidative stress in cancer.

DNA damage response (DDR) is a regulatory system responsible for maintaining genome integrity and stability, which can sense and transduce DNA damage signals. The severity of damage appears to determine DDRs, which can include damage repair, cell-cycle arrest, and apoptosis. Furthermore, defective components in DNA damage and repair machinery are an underlying cause for the development and progression of various types of cancers. Increasing evidence indicates that there is an association between trace elements and DDR/repair mechanisms. In fact, trace elements seem to affect mediators of DDR. Besides, it has been revealed that oxidative stress (OS) and trace elements are associated with cancer development. In this review, we discuss the role of some critical trace elements in the risk of cancer. In addition, we provide a brief introduction on DDR and OS in cancer. Finally, we will further review the interactions between some important trace elements including selenium, zinc, chromium, cadmium, and arsenic, and DDR, and OS in cancer.