The long pentraxin PTX3 in human endometrium: regulation by steroids and trophoblast products

Abstract

Human implantation is characterized by blastocyst attachment to endometrial epithelial cells followed by invasion of trophoblast into the maternal decidua. There has been an increasing amount of data linking higher levels of the pentraxin PTX3, a long pentraxin, to embryo implantation. PTX3 levels were found to be higher in patients with preeclampsia and intrauterine growth restriction, both conditions caused by faulty implantation. Furthermore, PTX3 knockout mice have reduced fertility due to cumulus oopherus malformation as well as implantation failure. In a human implantation model, we and others have shown that trophoblast action on endometrial stromal cells induces PTX3 expression. In this study, we analyzed PTX3 expression throughout the menstrual cycle as well as its regulation by hormones involved in the implantation process. We also compared PTX3 expression in stromal cells induced by trophoblast conditioned medium to its induction by trophoblast coculture. PTX3 mRNA expression in human endometrial stromal cells is regulated by progesterone, estrogen, and IL-1 but not human chorionic gonadotropin and is increased by both trophoblast-conditioned medium as well as trophoblast explants. PTX3 protein production and regulation by these factors is shown by Western blot. Based on these findings, we conclude that estradiol and progesterone are involved in PTX3 induction and regulation during implantation. Also, of the factors secreted by trophoblast, IL-1beta induces PTX3 in human endometrial stromal cells.