We also defined another subset that may play a key practical role in maintaining the state of “stemness”. Decidualization, the process by which progesterone acts on the estrogen-primed endometrium to convert precursor stromal cells into decidual cells, is essential for successful implantation and maintenance of pregnancy. The decidualization reaction is initiated in the perivascular stromal cells and under the influence of progesterone, spreads ‘wave-like’ throughout the stromal region. It is characterised by the phenotypic transformation of the elongated fibroblast-like endometrial stromal cells into a larger, spherical decidual cell. This change in cell shape is associated with rearrangements in cellular architecture, the accumulation of glycogen and increased expression of prolactin and Masitinib insulin growth factor binding protein 1. Studies using primary cultures of human endometrial stromal cells have revealed that this process is complex and likely to involve multiple factors including PGE2, relaxin and cAMP in addition to progesterone. A strong association exists between the degree of trophoblast invasion and the extent of decidualization in species with a hemochorial placenta. Not only does human trophoblast exhibit the greatest degree of trophoblast invasion observed in all species, but also human endometrium undergoes the most extensive decidualization reaction. Decidualized stromal cells are temporally and spatially positioned to promote local homeostasis during implantation and counteract the threat of haemorrhage during trophoblast invasion. Production of tissue factor by decidual cells is also thought to be important in preventing uterine bleeding in the peri-implantation phase of the cycle. It has been hypothesised that menstruation only occurs in species where the decidualization reaction is initiated spontaneously during each cycle regardless of the presence of a blastocyst. Although the classic “trigger” for the onset of menstruation is the withdrawal of progesterone associated with the demise of the corpus luteum, multiple cytokines and growth factors have been reported to play a role in this process. Based on several lines of evidence we have previously proposed that transforming growth factor b1, which canonically transduces its signal from type II serine/threonine kinase transmembrane receptors to the nucleus through the Sma- and mothers against decapentaplegic -related protein signalling cascade, might play a role in initiating the process of menstruation. For example, expression of TGFb1 is increased in stromal cells as they undergo decidualization. We have previously demonstrated that treatment of decidualized ESC with TGFb1 suppresses expression of progesterone receptor suggesting that TGFb1 may potentiate the effects of progesterone withdrawal. An enhanced understanding of local mechanisms involved in the regulation of endometrial events preceding menstruation is an essential prerequisite for delineating the aetiology of early pregnancy complications as well as abnormal endometrial tissue activity.