The mechanism by which endometriosis, a common gynecological disease characterized by chronic pelvic pain and infertility, causes infertility remains elusive. Luteinized unruptured follicle syndrome, the most common type of ovulatory dysfunction, is a cause of endometriosis-associated infertility involving reduced numbers of retrieved and mature oocytes. Ovulation is controlled by luteinizing hormone and paracrine signals produced within the follicle microenvironment. Generally, interleukin (IL)-1β is elevated in endometriosis follicular fluid, whereby it amplifies ovulation signals by activating extracellular-regulated kinase 1/2 and CCAAT/enhancer binding protein β pathways. However, this amplification of ovulation by IL-1β does not occur in patients with endometriosis. To illuminate the mechanism of ovulatory dysfunction in endometriosis, we analyzed the impact of oxidative stress and IL-1β expression in endometriosis follicles. We found that oxidative stress decreased EZH2 expression and reduced H3K27Me3 levels in endometriosis ovarian granulosa cells (GCs). Selective Ezh2 depletion in mice ovarian GCs reduced fertility by disturbing cumulus-oocyte complex expansion and reducing epidermal growth factor-like factor expression. Gene expression and H3K27Me3 ChIP-sequencing of GCs revealed IL-1 receptor 2 (IL-1R2), a high-affinity IL-1β-receptor that suppresses IL-1β-mediated inflammatory cascades during ovulation, as a crucial target gene of the EZH2-H3K27Me3 axis. Moreover, IL-1β addition did not restore ovulation upon Ezh2 knockdown, indicating a vital function of IL-1R2 in endometriosis. Thus, our findings show that reducing EZH2 and H3K27Me3 in GCs suppressed ovulatory signals by increasing IL-1R2 expression, which may ultimately contribute to endometriosis-associated infertility.
The protocols involving gonadotropin releasing hormone (GnRH)agonist (GnRH-a) have high rates of embryo implantation and clinical pregnancy. 1 Hence, these are the most commonly used controlled ovarian hyperstimulation (COH) protocols in China. However, the deficiencies of these schemes lead to an increase of ovarian hyperstimulation syndrome (OHSS) incidence). 2 In vitro maturation (IVM) is a simple, low-cost procedure that decreases the occurrence of OHSS. 3 Therefore, our center adopted a modified scheme including the timely switch from conventional in vitro fertilization (IVF) to IVM when patients undergoing COH
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.