M2 Macrophages are Major Mediators of Germline Risk of Endometriosis and Explain Pleiotropy With Comorbid Traits.

ABSTRACT: Endometriosis is a common gynecologic condition that causes chronic, life-altering symptoms including pain and infertility. There is an urgent need for new non-hormonal targeted therapeutics to treat endometriosis, but until very recently, the cellular and molecular signatures of endometriotic lesions are undefined, hindering the development of clinical advances. Integrating inherited risk data from analyses of >45 0000 individuals with ≈35 0000 single-cell transcriptomes from 21 patients, M2-macrophages as candidate drivers of disease susceptibility are uncovered, and nominating IL1 signaling as a central hub impacted by germline genetic variation associated with endometriosis risk. Extensive functional follow-up confirmed these associations and revealed a pleiotropic role for this pathwa

SUBMITTER: Ochoa S 

PROVIDER: S-EPMC12591210 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature