Implantation is attachment of trophectoderm (Tr) of the developing conceptus (the embryo and associated extraembryonic membranes) to the luminal epithelium (LE) of the uterus. This highly synchronized event requires reciprocal secretory and physical interactions between the conceptus and uterine endometrium during a restricted period known as the window of receptivity. The receptive state is established by critical levels of progesterone and estrogen that regulate locally produced cytokines, growth factors, homeobox transcription factors, and cyclooxygenase-derived prostaglandins through auto-crine and paracrine pathways. Initiation of endometrial receptivity also depends upon silencing expression of progesterone receptors (PR) in uterine LE and superficial gland epithelia, although PRs continue to be expressed in stroma and myometrium. Effects of progesterone on PR-negative epithelial cells appear to be mediated by various stromal cell-derived growth factors that function as progestamedins.
The initial interactions between apical uterine LE and Tr surfaces begin with sequential phases (i.e., nonadhesive or prereceptive, apposition, and attachment) and conclude with development of a placenta that supports fetal development throughout pregnancy. During the early phases of implantation, secretory products of both uterine glands (histotroph) and conceptus Tr exert a mutual influence. Histotroph provides nutritional support for conceptus development, which in turn promotes secretion of hormones and cytokines, including the signal for maternal recognition of pregnancy, which is obligatory to prolong progesterone production by the corpus luteum (CL) and maintain pregnancy.
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