*2.2. Decidualization*

In addition to the changes occurring in the luminal and glandular epithelium, major changes take place also in the endometrial stroma. The endometrial stromal cells undergo a decidual reaction, in which they proliferate and differentiate from fibroblast-like to epithelial-like cells, which will form the maternal decidua. Decidual cells progressively increase in size and number throughout pregnancy, starting from 9.8% of stromal cells in early pregnancy and arrive to 57.8% at term [67]. The acquisition of the epithelial-like phenotype by stromal cells consists in an increase in size, rounding of the nucleus with increased number of nucleoli, accumulation of glycogen, lipid droplets and secretory granules in the cytoplasm, and expansion of rough endoplasmic reticulum and Golgi apparatus [68]. The term "decidua" derives from Latin "de cadere" and means to fall down, so it refers to the fact that the decidualized uterine tissue is lost after parturition. Decidua is mainly formed by decidualized endometrial stromal cells, but also contains hematopoietic cells, macrophages, uterine natural killer (uNK) and monocytes [69,70]. Decidualization starts in the luteal phase, with stromal cells surrounding the spiral arteries in the upper two-thirds of the endometrium, regardless of whether or not the blastocyst is present [71]. Differently from most mammals, decidualization in humans occurs before the embryo reaches the uterine cavity and is driven by the postovulatory rise in progesterone levels and local increase of cyclic adenosine monophosphate (cAMP) production, occurring long before the embryo is ready to implant. In the absence of pregnancy, progesterone levels decrease, and menstrual shedding and cyclic regeneration of the endometrium occur. Decidualization is responsible for embryo quality control, promoting implantation and development, or facilitating early rejection in case, for example, of chromosomally abnormal human embryos [72,73].
