Single-cell transcriptomic atlas of ovarian endometriosis patient's follicular fluid: unraveling novel insights into abnormal follicular development.

In brief: We present the first single-cell transcriptomic atlas of follicular fluid from an ovarian endometrioma (OMA) patient, revealing a novel TCR+ macrophage subtype, aberrant granulosa cell developmental trajectories, immune dysregulation, and enhanced MIF/MK signaling, providing new insights into mechanisms underlying impaired follicular development in OMA. Abstract: Ovarian endometrioma (OMA), an endometriosis subtype, involves hemorrhagic cysts formed by ectopic endometrial-like tissue, causing pelvic pain, inflammation, and infertility by disrupting ovarian function. Despite its impact, the single-cell dynamics in OMA follicular fluid are poorly understood. We performed single-cell RNA sequencing (10x Genomics) on follicular fluid from a patient's affected (2,793 cells) and unaffected (4,699 cells; control) ovaries. Analysis revealed four cell types, including a novel TCR+ macrophage subtype. Affected-side granulosa cells showed abnormal developmental trajectories linked to dysregulated steroid pathways. Immune cells exhibited heightened inflammation and reduced macrophage phagocytosis. Cell-cell communication highlighted prominent Macrophage Migration Inhibitory Factor and Midkine signaling from granulosa cells. This study provides the first single-cell transcriptomic profile of OMA follicular fluid, elucidating aberrant granulosa cell development, immune dysregulation, and distinctive cellular interactions, enhancing understanding of OMA's impact on follicular development and suggesting potential diagnostic/therapeutic targets.