Decreased NOTCH1 signaling activated autophagy in the mid-secretory endometrium of patients with recurrent implantation failure† by Ziyao Yang

Biol Reprod. 2023 Mar 17:ioad034. doi: 10.1093/biolre/ioad034. Online ahead of print.

ABSTRACT

Recurrent implantation failure (RIF) severely impairs fertility in females of childbearing age, which poses a great challenge to assisted reproductive technology, and its etiology is still unclear. Several studies have demonstrated that endometrial autophagy takes an important part in human endometrial receptivity, but its role in RIF remains largely unknown. Here, we collected mid-secretory endometrial tissue from RIF patients, and fertile controls during menstruation and early pregnancy. Immunohistochemistry, Western blotting, and quantitative real-time PCR were performed to compare the expression of LC3B, p62, NOTCH1 signaling pathway members, and endometrial receptivity markers between RIF and control groups. In addition, to assess endometrial autophagy, transmission electron microscopy was used to observe autophagosomes. By RNA interference, we further investigated the effects of NOTCH1 on autophagy in Ishikawa cells. We found that endometrial autophagy was upregulated in the mid-secretory and decidual phases than in the early-proliferative phase. Compare to the control group, more autophagosomes were observed in the mid-secretory endometrium of RIF patients, accompanied by the downregulation of NOTCH1 signaling pathway members and endometrial receptivity markers. Moreover, knockdown of NOTCH1 impaired the receptivity of Ishikawa cells via AKT/mTOR pathway-mediated autophagy activation. Our data suggested that abnormally elevated autophagy and decreased NOTCH1 signaling pathway activity were observed in the mid-secretory endometrium of patients with recurrent implantation failure, perhaps due to decreased NOTCH1 pathway-mediated autophagy activation in endometrial cells impairing receptivity.

PMID:36930053 | DOI:10.1093/biolre/ioad034