Endometriosis: current challenges in modeling a multifactorial disease of unknown etiology

et al. 2021

Reprod Biol Endocrinol

Background Endometriosis is a chronic hormonal inflammatory disease characterized by the presence of endometrial tissue outside the uterus. Endometriosis often causes infertility, which brings physical and mental pain to patients and their families. Methods We examined the functions of heat shock factor 1 (HSF1) in endometriosis development through cell count assay, cell-scratch assay and clone formation experiments. We used quantitative real-time PCR (qRT-PCR) and Western blot (WB) to detect HSF1 expression. Glucose and lactate levels were determined using a glucose (GO) assay kit and a lactate assay kit. Furthermore, we used a HSF1 inhibitor-KRIBB11 to establish a mouse model of endometriosis. Results Our data demonstrated that HSF1 promoted endometriosis development. Interestingly, HSF1 enhanced glycolysis via up-regulating PFKFB3 expression in endometriosis cells, which was a key glycolysis enzyme. Consistently, the HSF1 inhibitor KRIBB11 could abrogate endometriosis progression in vivo and in vitro. Conclusions Findings indicate that HSF1 plays an important role in endometriosis development, which might become a new target for the treatment of endometriosis. Electronic supplementary material Supplementary data are available.

Section: Discussionmentioning

confidence: 99%

HSF1 promotes endometriosis development and glycolysis by up-regulating PFKFB3 expression

Wang

Xiu

et al. 2021

Reprod Biol Endocrinol

“…Endometriosis is an age-related disease of the reproductive system, and its prevalence is up to 10% in premenopausal women worldwide [6]. The diagnosis of endometriosis is di cult, because experienced obstetricians and gynecologists are required to assess the clinical symptoms of the disease and assess the existence of ectopic endometrium in the abdominal cavity and pelvis [30]. In recent years, more studies have been published on how to treat endometriosis.…”

Section: Discussionmentioning

confidence: 99%

HSF1 promotes endometriosis development and glycolysis by up-regulating PFKFB3 expression

Wang

Xiu

et al. 2021

Preprint

Background Endometriosis is a chronic hormonal inflammatory disease characterized by the presence of endometrial tissue outside the uterus. Endometriosis often causes infertility, which affects the body and mind of patients and their families.Methods We examined the functions of heat shock factor 1 (HSF1) in endometriosis development through cell count, scratch and clone formation experiments. We used quantitative real-time PCR (qRT-PCR) and Western blot (WB) to detect the functions of HSF1 in endometriosis cells. Glucose and lactate levels were determined using a glucose (GO) assay kit and a lactate assay kit. Furthermore, we established a mouse model of endometriosis by using a HSF1 inhibitor-KRIBB11.Results Our study demonstrated that HSF1 was highly expressed in endometriosis, and promoted endometriosis development. Interestingly, we found that HSF1 promoted glycolysis in endometriosis cells. Further, HSF1 enhanced glycolysis by up-regulating PFKFB3 in endometriosis cells, which was a key enzyme in glucose metabolism. Moreover, the HSF1 inhibitor KRIBB11 could abrogate endometriosis progression in vivo and in vitro.Conclusions Findings indicate that HSF1 plays an important role in the development of endometriosis, which might become a new target for the treatment of endometriosis and provide a new idea for the clinical treatment of endometriosis.Electronic supplementary material Supplementary data are available.

“…Endometriosis is an enigmatic disease affecting mainly reproductive-aged women because of pain and declined fertility. The treatment effect is dissatis ed on account of uncertainty of its pathogenesis [16,17]. Exploring the subtle mechanism and identifying new molecular targets are needed to bring promise for more effective treatment.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Circ_0000673 Promotes Cell Proliferation and Migration in Endometriosis Via Suppressing PTEN

Ban

Zhang

et al. 2021

Preprint

Background: Endometriosis is a prevalent gynecologic disease, affecting up to 10% of women at reproductive age and approximately 50% of women with infertility. The function of circRNAs in various diseases has been highlighted. Dysregulated expression of circRNAs in endometriosis has been reported and circ_0000673 was significantly deregulated. However, its explicit role in pathogenesis of endometriosis is yet to be identified. Methods: circ_0000673 expression was detected in paried ectopic and eutopic endometrium using qPCR and fluorescent in situ hybridization. Knockdown of circ_0000673 in eutopic and normal endometrial stromal cells were done by transfection with lentivirus vectors. The proliferation activity of endometrial stromal cells was evaluated by CCK-8 assay and colony formation assay, while the migration capacity was valued by wound healing assay. PTEN, PI3K and p-AKT were detected by qPCR and western blotting. Dual luciferase assay was performed to assess the bonding between circ_0000673, PTEN and miR-616-3p.Results: The expression of circ_0000673 was reduced in ectopic endometrium. Knockdown of circ_0000673 significantly induced eutopic and normal endometrial cell proliferation and migration. Bioinformatic analysis predicted that circ_0000673 might sponge miR-616-3p. The effect of circ_0000673 knockdown could be recovered by miR-616-3p inhibitor and enhanced by miR-616-3p mimics. Meanwhile, qPCR and western blotting showed that circ_0000673 knockdown inhibited the expression of PTEN, and subsequently activated PI3K and p-Akt. Furthermore, PTEN was confirmed to be a target of miR-616-3p. Conclusion: The results demonstrated that deregulated expression of circ_0000673 could promote endometriosis progression via sponging miR-616-3p and further regulating PTEN.