Clusterin from endometrial glands plays a critical role in decidualization via Trem2.

Background: Decidualization is a critical step in establishing pregnancy in mammals. Successful decidualization depends on intricate gland-stromal crosstalk. Clusterin (Clu) is a ubiquitously secreted protein in physiological fluids that is involved in numerous physiological functions. However, the role of Clu in decidualization is not fully understood.

Results: In this study, we examined the expression pattern of Clu during early pregnancy in mice and explored its potential function in decidualization. Our results revealed that Clu was expressed in the uterine glands on Days 1-2 of early pregnancy and on Days 5-8 during decidualization after embryo implantation, as well as in glands at the interimplantation site. Additionally, ovariectomized mice exhibited significant upregulation of Clu expression in the uterine glands 3 h after in vivo estrogen injection. Trem2, a receptor for Clu, was detected in the decidual region of mice on Days 5-8 of early pregnancy, where it mediates Clu to regulate the decidual region. Furthermore, we observed that recombinant CLU protein increased the expression of the decidualization marker molecules insulin-like growth factor binding protein 1 (IGFBP1) and prolactin (PRL) in decidual cells. However, this upregulation was not observed when Trem2 expression was inhibited with siRNA.

Conclusions: Uterine gland-derived Clu, a new paracrine modulator, may participate in early pregnancy by influencing the decidualization process mediated by Trem2 in mice.