Endometrial senescence: inevitability and conditional occurrence in female fertility

Abstract: The endometrium is the primary site of embryo implantation. Cellular senescence within the endometrium can be broadly categorised into normal cyclical senescence and pathological excessive senescence. Normal cyclical senescence occurs as a normal component of the female reproductive cycle and contributes to endometrial receptivity for embryo implantation. In contrast, pathological excessive senescence arises in response to excessive external stimuli. This process may propagate between cells, impair immune-mediated clearance, and reduce the efficacy of senolytic therapies. This review aims to summarise the physiological and pathological endometrial cell senescence, as well as current therapeutic strategies targeting this process, thereby providing a theoretical framework and directions for future clinical research. Lay summary: Cells, like humans, also undergo aging. The aging cells in the uterine lining are cleared by the immune system to maintain the stability of the uterus. However, external stimulation can disrupt the balance, and increase the possibility of female infertility. This type of cell aging is reversible, unlike the aging caused by the passage of time. This article reviews uterine aging under both normal and abnormal conditions and the current treatment methods for reversing cell aging, providing a new perspective for clinical treatment of female infertility in the future.