Effectiveness of NLRP3 Inhibitor as a Non-Hormonal Treatment for Ovarian Endometriosis

Mayuko Murakami, Satoko Osuka, Ayako Muraoka, Shotaro Hayashi, Bayasula Bayasula, Yukiyo Kasahara, Reina Sonehara, Yumi Hariyama, Kanako Shinjo, Hideaki Tanaka, Natsuki Miyake, Sayako Yoshita, Natsuki Nakanishi, Tomoko Nakamura, Maki Goto, Hiroaki Kajiyama
In: Research Square · 2021 · doi:10.21203/rs.3.rs-1062370/v1 · W4200167088
preprint OA: green CC0 ⤵ 2 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

NLRP3 inflammasome inhibition with MCC950 reduced ovarian endometriosis lesion size and improved ovarian function in a mouse model by decreasing IL-1β and oxidative stress.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-10 ⓘ

This preprint evaluated whether inhibiting the NLRP3 inflammasome with the small-molecule inhibitor MCC950 could serve as a non-hormonal therapy for ovarian endometriosis by measuring NLRP3/IL-1β biology in human tissues and cell models, and then testing MCC950 in a murine model. In patients, NLRP3 gene and protein expression were higher in ovarian endometriosis lesions and in cyst-derived stromal cells than in eutopic endometrium and eutopic stromal cells, and MCC950 reduced cyst-derived stromal cell survival while decreasing NLRP3–IL-1β co-localization and IL-1β secretion, with reduced ovarian endometriosis lesion size and lower IL-1β, Ki67, and granulosa cell oxidative stress markers in mice. The authors explicitly note the study is a preprint that has not been peer reviewed. This paper is centrally about endometriosis — specifically ovarian endometriosis and non-hormonal targeting of the NLRP3/IL-1β inflammatory pathway with MCC950.

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Abstract

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 for endometriosis suppress ovulation; hence, they are not compatible with fertility. The inflammasome is a complex that includes Nod-like receptor (NLR) family proteins that sense pathogen-/danger‐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 the inhibitors of the NLRP3 inflammasome. Methods The expression of NLRP3 was measured in the eutopic endometrium (EM) of patients with/without endometriosis and OE and stromal cells derived from the endometrium of patients with endometriosis and OE (endometrial stromal cells [ESCs] and cyst-derived stromal cells [CSCs]). The effect of an NLRP3 inhibitor (MCC950) on ESC and CSC survival and IL-1β production was 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 and IL-1β concentrations in CSC supernatants. In the murine model, MCC950 treatment reduced OE lesion size compared to phosphate-buffered saline treatment (89 ± 15 vs. 49 ± 9.3 mm 3 per ovary; P < 0.05). In addition, IL-1β and Ki67 levels in the OE-associated epithelia and oxidative stress markers of granulosa cells were reduced in the MCC950-treated group. Conclusions These results indicate 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.

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Condition tags

endometriosisdysmenorrheainfertility

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

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