The activation of cGAS-STING pathway causes abnormal uterine receptivity in aged mice.
Abstract
Maternal age is one of the most important factors affecting the success of maternal pregnancy. Uterine aging is the leading cause of pregnancy failure in older women. However, how uterine aging affects uterine receptivity and decidualization is unclear. In this study, naturally aged one-year-old female mice were used to investigate effects of maternal age on embryo implantation during early pregnancy. In our study, we found abnormal uterine receptivity in aged mice. Aged mouse uterus indicates a decrease in nuclear LAMIN A, and an increase in PRELAMIN A and PROGERIN. In aged mouse uterus, double-stranded DNA (dsDNA) in cytoplasmic fraction is significantly increased. PROGERIN overexpression in mouse uterine epithelial cells and epithelial organoids leads to nuclear DNA leakage and impaired uterine receptivity. DNase I, DNase II, and TREX1 are obviously reduced in aged mouse uterus. Treatments with foreign DNA or STING agonist significantly downregulate uterine receptivity markers and activate cGAS-STING pathway. Uterine estrogen (E
The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.
Research summary
The paper investigates the mechanisms underlying uterine aging and its effects on receptivity, which is relevant to the broader context of aging and reproductive health. However, while it provides insights into the biological processes involved, the findings are more focused on understanding symptoms of aging rather than addressing root causes or potential interventions for lifespan extension. Thus, the impact is solid but limited.
Author of this paper? Send a correction.