CBLL1 promotes endometrial stromal cell senescence via inhibiting PTEN in recurrent spontaneous abortion

Cellular senescence of human endometrial stromal cells (HESCs) is one of the important mechanisms underlying RSA. We have demonstrated that CBLL1 overexpression promoted HESCs senescence and knockout of CBLL1 alleviated cellular senescence induced by oxidative inducers. Transcriptomic sequencing results and further research revealed PTEN as one of the important downstream target genes of CBLL1, and upregulation of CBLL1 led to downregulation of PTEN. Knockdown of PTEN promoted HESCs senescence, elevated oxidative stress, and inhibited proliferation. CBLL1 overexpression induced-cellular senescence was rescued by overexpression of PTEN. In vivo experiments demonstrated that overexpression of CBLL1 in the endometrium significantly increased the embryo absorption rate in mice. In conclusion, our findings discovered that elevated CBLL1 expression is a significant contributor to RSA, and its mechanism may be related to the elevation of CBLL1 leading to a decrease in PTEN, resulting in the senescence of HESCs. This finding could provide new avenues for treatment of RSA. Overall design: To investigate the role of CBLL1 in regulating endometrial stromal cell function, we established HESC cell lines in which CBLL1 has been overexpressed by lentivirus.