Implantation, Pregnancy and Parturition
(T593) INVOLVEMENT OF STATHMIN IN HUMAN ENDOMETRIAL STROMAL CELL DECIDUALIZATION.
Yoshie, Mikihiro1, Tamura, Kazuhiro1, Hara, Takahiko2, Kogo, Hiroshi1, 1 Tokyo University of Pharmacy & Life Science, Tokyo, Japan2 The Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
ABSTRACT- Human endometrial stromal cells (ESCs) differentiate into decidualized stromal cells during the secretory phase of the menstrual cycle and pregnancy. Decidualization is necessary for embryo implantation and the maintenance of pregnancy. This differentiation can be induced in vitro by several factors including progesterone which are coupled to the cAMP pathway. Stathmin, a cytosolic phosphoprotein that regulates cell cycle progression and tubulin dynamics, is expressed in ESCs and glandular epithelium in human uterus. During the menstrual cycle, stathmin mRNA expression was relatively higher in the secretory phase compared to that in the proliferation phase. In a primary culture of human ESCs, stathmin protein gradually decreased with the progress of ovarian steroids-induced decidualization. To examine a role of stathmin in the progression of stromal cell differentiation, we have established an immortalized human ESC line (EtsT) by introducing the temperature-sensitive mutant of the SV 40 T antigen in primary ESCs. This cell line exhibited a fibroblast-like morphology that was similar to primary ESCs. By treatment with dibutyryl-cAMP (db-cAMP) or with forskolin, EtsT cells were differentiated with an epithelioid-like shape and produced high amounts of decidual markers, IGF binding protein-1 (IGFBP-1) and prolactin. Consistent with the observations in primary ESCs, the levels of stathmin protein decreased during the db-cAMP- or forskolin-induced decidualization in EtsT. Furthermore, the knock-down of the endogenous stathmin mRNA by small interfering RNA significantly suppressed the mRNA expression and the secretion of both IGFBP-1 and prolactin in the db-cAMP-treated EtsT cells. These results first revealed an essential role of stathmin in the process of decidualization in human endometrial stromal cells.
KEY WORDS: endometrium, decidualization, stathmin