Decorin production by the human decidua: role in decidual cell maturation.

Decidualization involves the proliferation and differentiation of fibroblast-like endometrial stromal cells into epithelioid-shaped and secretory "decidual" cells in response to steroid hormones. Human decidual cells produce insulin-like-growth-factor-binding-protein-1 and prolactin, two well-recognized markers of decidual cell maturation, and a proteoglycan decorin. We reported that decorin restrains the human trophoblast renewal, migration, invasion and endovascular differentiation needed for uterine arterial remodelling during normal pregnancy. Decorin overproduction by the decidua is associated with a hypo-invasive placenta and a serious pregnancy disorder, pre-eclampsia. Furthermore, elevated maternal plasma decorin levels during the second trimester is a predictive biomarker of pre-eclampsia. While these paracrine roles of decidua-derived decorin on trophoblast physiology and pathology have been well-defined, it remains unknown whether decorin plays any autocrine role in decidual cell development. The objectives of this study were to examine: the kinetics of decorin production during decidualization of human endometrial stromal cells; gestational age-related changes in decorin production by the first trimester decidua; and a possible autocrine role of decorin on decidual cell maturation. We found that decorin production is enhanced during decidualization of both primary and immortalized human endometrial stromal cells in vitro and during early gestation in decidual samples tested ex-vivo, and that it is important for endometrial stromal cell maturation into a decidual phenotype. Decorin-depleted human endometrial stromal cells exposed to decidualizing stimuli failed to mature fully, as evidenced by fibroblastoid morphology, reduced insulin-like-growth-factor-binding-protein-1 and prolactin expression, and reduction in cellular ploidy. We identified heart-and-neural-crest-derivatives-expressed-protein-2, and progesterone receptor as potential downstream mediators of decorin effects.