Effectiveness of NLRP3 Inhibitor as a Non-Hormonal Treatment for ovarian endometriosis
Abstract Background Endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects 10% of women of reproductive age. Ovarian endometriosis (OE) is the most common lesion in endometriosis and may cause infertility, in addition to dysmenorrhea. Hor...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-03-01
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| Series: | Reproductive Biology and Endocrinology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12958-022-00924-3 |
| _version_ | 1811311659072880640 |
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| author | Mayuko Murakami Satoko Osuka Ayako Muraoka Shotaro Hayashi Bayasula Yukiyo Kasahara Reina Sonehara Yumi Hariyama Kanako Shinjo Hideaki Tanaka Natsuki Miyake Sayako Yoshita Natsuki Nakanishi Tomoko Nakamura Maki Goto Hiroaki Kajiyama |
| author_facet | Mayuko Murakami Satoko Osuka Ayako Muraoka Shotaro Hayashi Bayasula Yukiyo Kasahara Reina Sonehara Yumi Hariyama Kanako Shinjo Hideaki Tanaka Natsuki Miyake Sayako Yoshita Natsuki Nakanishi Tomoko Nakamura Maki Goto Hiroaki Kajiyama |
| author_sort | Mayuko Murakami |
| collection | DOAJ |
| description | Abstract Background Endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects 10% of women of reproductive age. Ovarian endometriosis (OE) is the most common lesion in endometriosis and may cause infertility, in addition to dysmenorrhea. Hormonal treatments, which are the conventional treatment methods for endometriosis, suppress ovulation and hence are not compatible with fertility. The inflammasome is a complex that includes Nod-like receptor (NLR) family proteins, which sense pathogen-associated molecular patterns and homeostasis-altering molecular processes. It has been reported that the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing (NLRP) 3 inflammasome, which contributes to the activation of interleukin-1 beta (IL-1β), might be related to the progression of endometriosis. Therefore, the aim of the present study was to evaluate non-hormonal therapies for OE, such as inhibitors of the NLRP3 inflammasome. Methods The expression of NLRP3 was measured in the eutopic endometrium (EM) of patients with and without endometriosis and OE samples, as well as stromal cells derived from the endometrium of patients with and without endometriosis and OE samples (endometrial stromal cells with endometriosis [ESCs] and cyst-derived stromal cells [CSCs]). The effects of an NLRP3 inhibitor (MCC950) on ESCs and CSCs survival and IL-1β production were evaluated. We then administered MCC950 to a murine model of OE to evaluate its effects on OE lesions and ovarian function. Results NLRP3 gene and protein expression levels were higher in OE and CSCs than in EM and ESCs, respectively. MCC950 treatment significantly reduced the survival of CSCs, but not that of ESCs. Moreover, MCC950 treatment reduced the co-localization of NLRP3 and IL-1β in CSCs, as well as IL-1β concentrations in CSCs supernatants. In the murine model, MCC950 treatment reduced OE lesion size compared to phosphate-buffered saline treatment (89 ± 15 vs. 49 ± 9.3 mm3 per ovary; P < 0.05). In the MCC950-treated group, IL-1β and Ki67 levels in the OE-associated epithelia were reduced along with the oxidative stress markers of granulosa cells. Conclusions These results indicated that NLRP3/IL-1β is involved in the pathogenesis of endometriosis and that NLRP3 inhibitors may be useful for suppressing OE and improving the function of ovaries with endometriosis. |
| first_indexed | 2024-04-13T10:22:47Z |
| format | Article |
| id | doaj.art-433c582f40344f0583e14bf0be379eab |
| institution | Directory Open Access Journal |
| issn | 1477-7827 |
| language | English |
| last_indexed | 2024-04-13T10:22:47Z |
| publishDate | 2022-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Reproductive Biology and Endocrinology |
| spelling | doaj.art-433c582f40344f0583e14bf0be379eab2022-12-22T02:50:26ZengBMCReproductive Biology and Endocrinology1477-78272022-03-0120111210.1186/s12958-022-00924-3Effectiveness of NLRP3 Inhibitor as a Non-Hormonal Treatment for ovarian endometriosisMayuko Murakami0Satoko Osuka1Ayako Muraoka2Shotaro Hayashi3Bayasula4Yukiyo Kasahara5Reina Sonehara6Yumi Hariyama7Kanako Shinjo8Hideaki Tanaka9Natsuki Miyake10Sayako Yoshita11Natsuki Nakanishi12Tomoko Nakamura13Maki Goto14Hiroaki Kajiyama15Department of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineBell Research Center for Reproductive Health and Cancer, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Toyota Kosei HospitalDepartment of Obstetrics and Gynecology, Toyota Kosei HospitalDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineAbstract Background Endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects 10% of women of reproductive age. Ovarian endometriosis (OE) is the most common lesion in endometriosis and may cause infertility, in addition to dysmenorrhea. Hormonal treatments, which are the conventional treatment methods for endometriosis, suppress ovulation and hence are not compatible with fertility. The inflammasome is a complex that includes Nod-like receptor (NLR) family proteins, which sense pathogen-associated molecular patterns and homeostasis-altering molecular processes. It has been reported that the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing (NLRP) 3 inflammasome, which contributes to the activation of interleukin-1 beta (IL-1β), might be related to the progression of endometriosis. Therefore, the aim of the present study was to evaluate non-hormonal therapies for OE, such as inhibitors of the NLRP3 inflammasome. Methods The expression of NLRP3 was measured in the eutopic endometrium (EM) of patients with and without endometriosis and OE samples, as well as stromal cells derived from the endometrium of patients with and without endometriosis and OE samples (endometrial stromal cells with endometriosis [ESCs] and cyst-derived stromal cells [CSCs]). The effects of an NLRP3 inhibitor (MCC950) on ESCs and CSCs survival and IL-1β production were evaluated. We then administered MCC950 to a murine model of OE to evaluate its effects on OE lesions and ovarian function. Results NLRP3 gene and protein expression levels were higher in OE and CSCs than in EM and ESCs, respectively. MCC950 treatment significantly reduced the survival of CSCs, but not that of ESCs. Moreover, MCC950 treatment reduced the co-localization of NLRP3 and IL-1β in CSCs, as well as IL-1β concentrations in CSCs supernatants. In the murine model, MCC950 treatment reduced OE lesion size compared to phosphate-buffered saline treatment (89 ± 15 vs. 49 ± 9.3 mm3 per ovary; P < 0.05). In the MCC950-treated group, IL-1β and Ki67 levels in the OE-associated epithelia were reduced along with the oxidative stress markers of granulosa cells. Conclusions These results indicated that NLRP3/IL-1β is involved in the pathogenesis of endometriosis and that NLRP3 inhibitors may be useful for suppressing OE and improving the function of ovaries with endometriosis.https://doi.org/10.1186/s12958-022-00924-3EndometriosisInfertilityNLRP3 inflammasomeMCC950Non-hormonal therapiesIL-1β |
| spellingShingle | Mayuko Murakami Satoko Osuka Ayako Muraoka Shotaro Hayashi Bayasula Yukiyo Kasahara Reina Sonehara Yumi Hariyama Kanako Shinjo Hideaki Tanaka Natsuki Miyake Sayako Yoshita Natsuki Nakanishi Tomoko Nakamura Maki Goto Hiroaki Kajiyama Effectiveness of NLRP3 Inhibitor as a Non-Hormonal Treatment for ovarian endometriosis Reproductive Biology and Endocrinology Endometriosis Infertility NLRP3 inflammasome MCC950 Non-hormonal therapies IL-1β |
| title | Effectiveness of NLRP3 Inhibitor as a Non-Hormonal Treatment for ovarian endometriosis |
| title_full | Effectiveness of NLRP3 Inhibitor as a Non-Hormonal Treatment for ovarian endometriosis |
| title_fullStr | Effectiveness of NLRP3 Inhibitor as a Non-Hormonal Treatment for ovarian endometriosis |
| title_full_unstemmed | Effectiveness of NLRP3 Inhibitor as a Non-Hormonal Treatment for ovarian endometriosis |
| title_short | Effectiveness of NLRP3 Inhibitor as a Non-Hormonal Treatment for ovarian endometriosis |
| title_sort | effectiveness of nlrp3 inhibitor as a non hormonal treatment for ovarian endometriosis |
| topic | Endometriosis Infertility NLRP3 inflammasome MCC950 Non-hormonal therapies IL-1β |
| url | https://doi.org/10.1186/s12958-022-00924-3 |
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