Time of Implantation of the Conceptus and Loss of Pregnancy

Molecular complexity in establishing uterine receptivity and implantation

“…Therefore, failure to achieve on-time implantation is a risk factor for normal pregnancy outcome. This is clinically relevant as well, since implantation beyond the normal window of implantation in humans leads to spontaneous pregnancy losses [21]. An arduous task before us is to unravel the intricate nature of the signaling pathways in implantation.…”

“…Definitive evidence for the roles of these genes in implantation and/or decidualization has been forthcoming from an array of mouse gene knockout models [19]. Recent evidence suggests that a short delay in the attachment reaction produces an adverse ripple effect throughout pregnancy, with aberrant spacing of embryos, defective placentation, resorption, and retarded development of fetuses, ultimately giving rise to a poor pregnancy outcome [20][21][22]. This concept of timing as a crucial component of normal feto-placental development and determinant of pregnancy outcome comprises a novel theme whereby early embryo-uterine interaction directs the developmental programming for the remainder of gestation.…”

“…More important, studies with cPLA 2a -/-mice instigated the novel ripple effect hypothesis during the course of pregnancy, i.e., blastocysts implanting beyond the normal window of receptivity create an adverse ripple effect throughout the course of pregnancy. This ripple effect leads to aberrant uterine spacing of embryos, defective placentation, resorption, and retarded development of fetuses ultimately giving rise to poor pregnancy outcome [20,21]. Recently, another knockout mouse model exhibiting a similar phenotype has been reported.…”

What about superfertility, decidualization, and natural selection?

“…Major secretory products of decidual stromal cells include prolactin and insulin-like growth factor binding protein-1 (IGFBP-1), two proteins that have been used as markers of decidualization [9]. In humans, decidualization begins approximately 6 days after ovulation at the onset of the putative window of implantation which is thought to last not more than 2-4 days [10]. One effect of abnormal decidualization has been postulated to result in a prolongation of the window of implantation [2][3][4][5][6][7].…”

Expression of adhesion molecules during normal pregnancy

“…Appropriate endometrial development is known to be essential for normal implantation (Wilcox et al 1999). In most animals, the endometrium is thought to undergo a series of changes in response to ovarian steroids leading to the window of implantation (Simon and Valbuena 1999;Cross et al 1994).…”