Human embryo implantation

Abstract

Embryo implantation in humans is interstitial, meaning the entire conceptus embeds in the endometrium before the placental trophoblast invades beyond the uterine mucosa into the underlying inner myometrium. Once implanted, embryo survival pivots on the transformation of the endometrium into an anti-inflammatory placental bed, termed decidua, under homeostatic control of uterine natural killer cells. Here, we examine the evolutionary context of embryo implantation and elaborate on uterine remodelling before and after conception in humans. We also discuss the interactions between the embryo and the decidualising endometrium that regulate interstitial implantation and determine embryo fitness. Together, this Review highlights the precarious but adaptable nature of the implantation process.

Steroid receptor coactivator‐2 drives epithelial reprogramming that enables murine embryo implantation

“…In both the human and mouse, pregnancy establishment relies on the implantation of a high quality blastocyst into a receptive endometrium in which the latter's luminal epithelium is the first contact site for the blastocyst. 17,63 To facilitate blastocyst attachment and adhesion to the luminal epithelium, the epithelium undergoes a set of cellular and molecular changes, many of which promote a PMT state that is crucial for embryo implantation. 51,52 For uterine receptivity to manifest, apical alterations of the luminal epithelium occur in which its extracellular glycoprotein composition is changed and cell surface charge reduced to enable embryo attachment and adherence.…”

“…In both the human and mouse, pregnancy establishment relies on the implantation of a high quality blastocyst into a receptive endometrium in which the latter's luminal epithelium is the first contact site for the blastocyst 17,63 . To facilitate blastocyst attachment and adhesion to the luminal epithelium, the epithelium undergoes a set of cellular and molecular changes, many of which promote a PMT state that is crucial for embryo implantation 51,52 .…”

Spatial targeting of the prostaglandin receptor EP2 to very early endosomes co-ordinates PGE2-mediated cAMP signaling in decidualizing human endometrium

“…The human endometrium undergoes profound and dynamic remodeling across the menstrual cycle, with changes marked by cyclical phases of menstrual repair, estrogen-dependent proliferation, progesterone-dependent differentiation and senescence-like tissue break-down and shedding. 1,2 In particular, the process of decidualization, denoting the differentiation of endometrial stromal fibroblasts into specialized secretory decidual cells, occurs during the secretory phase of the menstrual cycle after ovulation, concomitant with the secretory transformation of endometrial glands, vascular remodeling, and immune cell recruitment. The process creates a supportive and nutritive environment that is indispensable for embryo implantation, placentation and pregnancy.…”

Convergent gene expression in epithelial cells illuminates the evolution of uterine receptivity

“…The tissular structures and cellular composition of the uterus are conserved across mammals, as is the overall sequence of the hormonal cycle; however, mammalian evolution is also marked by important differences in uterine morphology and physiology between species (Machado, Ontiveros, and Behringer 2022). These shifts include different mechanisms of embryo attachment and implantation into the receptive maternal endometrium (Muter et al 2023; Siriwardena and Boroviak 2022; McGowen et al 2014), as well as dramatic differences in placental invasivity into the uterine wall and in placental structures (Roberts, Green, and Schulz 2016; Carter and Enders 2004). Capturing and comparing the molecular tenets of these time- and hormone-dependent processes in vivo across multiple species remains a major challenge.…”

“…Transcriptomic comparisons of endometrial stromal cell lines across species have illuminated the functional bases of key mammalian adaptations such as decidualization (Lynch et al 2011; Erkenbrack et al 2018; Mika et al 2022). How endometrial epithelial cells have evolved remains however largely unexplored (Muter et al 2023). The endometrial epithelium, a continuous epithelial cell layer lining the uterine lumen and glands, plays fundamental roles in embryo recognition and early implantation (Muter et al 2023), stromal decidualization (Filant and Spencer 2013), and immunity against pathogens in the uterine cavity (King, Critchley, and Kelly 2003).…”