High Stromal Senescence During the Window of Implantation Is Linked to Plasma Cell Presence and Cluster Formation in the Endometrium

Successful implantation requires a finely regulated endometrial microenvironment during the window of implantation. Chronic endometritis, defined by plasma cell infiltration, and stromal senescence, indicated by p16 expression, represent separate but potentially interacting mechanisms associated with impaired endometrial receptivity. The relationship between these processes remains poorly understood. We aim to examine whether stromal senescence is associated with plasma cell density and clustering in the human endometrium during the implantation window. Forty mid-luteal (LH+7) endometrial biopsies were retrospectively analyzed and stratified into low-senescence (<0.5% stromal p16+ cells, n = 20) and high-senescence (>3.5%, n = 20) groups. Plasma cells were identified by immunohistochemistry for MUM1 and CD138 and quantified using HALO® software (version 3.4). Group comparisons were performed using Student’s t-test and chi-squared analysis. CD138+ plasma cells were significantly more abundant in high-senescence endometria than in low-senescence controls (0.065 ± 0.10 vs. 0.014 ± 0.027 cells/mm2, p = 0.02). Only MUM1+ cells formed stromal clusters, which were more frequent in high-senescence samples (67% vs. 31%, p = 0.05). High endometrial stromal senescence during the implantation window is associated with increased plasma cell infiltration and clustering. This interplay may contribute to chronic endometritis and impaired receptivity, providing new insights into potential diagnostic and therapeutic strategies for reproductive failure.