Senescent endometrial stromal cells transmit reactive oxygen species to the trophoblast-like cells and impair spreading of blastocyst-like spheroids

Successful implantation requires a fine-tuned dialog between the invading embryo and the maternal endometrium. Recently, we discovered that premature senescence of endometrial stromal cells (EnSC) might mediate improper decidual transformation of endometrial tissue and impair endometrial-blastocyst interaction. Here, we show that senescent EnSC are characterized by elevated intracellular reactive oxygen species (ROS) levels that originate from mitochondrial dysfunction and insufficient antioxidant defense. Decidualization of senescent EnSC is defective and is accompanied by the elevated intracellular and mitochondrial ROS levels. Antioxidant defense during decidualization is significantly less efficient in senescent EnSC compared to healthy ones. Senescent EnSC secrete increased amounts of ROS into the extracellular space. Elevated ROS released by senescent EnSC shift the redox balance and induce DNA damage in the neighboring trophoblast-like cells. In an in vitro implantation model, we observed impaired spreading of blastocyst-like spheroids into a monolayer of decidualizing senescent EnSC, which could be compensated by pretreatment of the senescent cells with the antioxidant, Tempol. Hence, we propose a possible mechanism that might be responsible, at least in part, for the defective embryo implantation realized via ROS transmitting from senescent EnSC to trophoblast cells. Such transmission results in the accumulation of ROS and subsequent DNA damage in trophoblastic cells, which might lead to improper migration and invasion of an embryo. In light of these findings, the application of antioxidants prior to implantation might be a promising strategy to improve implantation efficiency.

Automated summary

Successful implantation requires a finely tuned dialog between the invading embryo and the maternal endometrium. Premature senescence of endometrial stromal cells (EnSC) can lead to defective decidual transformation and impaired endometrial-blastocyst interaction. Senescent EnSC exhibit elevated intracellular reactive oxygen species (ROS) levels, originating from mitochondrial dysfunction and insufficient antioxidant defense. This imbalance in ROS release affects neighboring trophoblast-like cells, leading to DNA damage and potentially impacting embryo migration and invasion.