Bioactive factors in endometriosis peritoneal fluid remodel human cardiomyocytes

Endometriosis is associated with increased cardiovascular disease (CVD) risk, yet the cellular basis for this relationship remains unclear. We examined whether peritoneal fluid (PF) from women with endometriosis alters cardiomyocyte behavior in vitro. Human-induced pluripotent stem cell-derived cardiomyocytes were exposed for 48 h to standard or hypertrophic media supplemented with peritoneal fluid from endometriosis or control patients. Beating frequency was measured using calcium transient imaging, differential gene expression was assessed with the Human CVD-PCR array, and sarcomere features were quantified using gray-level cooccurrence matrix (GLCM)-based texture analysis. Under standard conditions, PF increased beats per minute compared with media alone (control P = 0.0006; endometriosis P < 0.0001), and beating frequency was higher with endometriosis PF than with control PF (P = 0.0214). Sarcomere length increased, and organization metrics reduced following PF (endo and ctrl) exposure under baseline conditions (P < 0.0001), suggesting remodeling. CVD array showed that >40% of the genes were altered by Endo-PF vs. <10% by control-PF, compared with media-alone treatment. Network analysis showed enrichment of adrenoceptor and G protein-coupled receptor signaling pathways. An increased expression of STAT1 (2.49-fold, P = 0.016) and reduced G0S2 (-5.24-fold, P = 0.037), along with regulation of MYH6 and NPR2, was seen when Endo-PF was compared with Ctrl-PF. In hypertrophic media, PF treatment produced significant differences in sarcomere organization. Outcomes were condition-dependent rather than uniformly significant. Endometriosis-associated PF shifts in cardiomyocyte function, gene expression, and sarcomere structure. This supports a cell-intrinsic link between endometriosis and altered cardiac signaling states and carries implications concerning long-term cardiovascular morbidity and mortality in women with endometriosis.NEW & NOTEWORTHY Endometriosis is linked to cardiovascular disease, but its direct effects on the heart are not well understood, reflecting broader mechanistic gaps in the disease. This study shows that exposure to peritoneal fluid (PF) from women with endometriosis is sufficient to change human cardiomyocyte beating frequency, sarcomere organization, and cardiovascular disease-associated gene expression in vitro. These findings support a cell-intrinsic mechanism through which endometriosis-associated factors may influence cardiac signaling and structure, extending beyond or supporting epidemiologic associations.