Endometrial NCOR1 deficiency contributes to implantation failure in endometriosis-associated infertility

Endometriosis-associated infertility is a complex condition in which the presence of endometrial-like tissue disrupts implantation and early pregnancy. Epigenetic regulators are critical for implantation and decidualization, yet their contribution to endometriosis-associated infertility remains incompletely understood. Nuclear receptor corepressor 1 (NCOR1), an epigenetic coregulator of steroid hormone signaling, has an incompletely defined role in endometriosis and early pregnancy. We show that NCOR1 expression is significantly reduced in the eutopic endometrium of infertile women with endometriosis. Using a conditional uterine Ncor1-knockout mouse model (Pgrcre/+Ncor1f/f), we demonstrate that NCOR1 loss is associated with increased ectopic lesion burden, implantation failure, defective decidualization, and severe subfertility, despite normal ovarian hormone production. NCOR1 deficiency was associated with disrupted progesterone-responsive signaling and endometrial receptivity. Together, these findings identify NCOR1 as an important regulator of endometrial function during early pregnancy and support an association between reduced NCOR1 expression and endometriosis-associated infertility.