The Role of Conceptus-maternal Signalling in the Acquisition of Uterine Receptivity to Implantation in Mammals

Implantation is a pivotal step in the establishment of mammalian pregnancy. Although implantation strategies vary between species, many aspects of conceptus-maternal signalling necessary to induce uterine receptivity to implantation are conserved. The temporal 'window' for the initiation of implantation is short and precisely controlled by endocrine, paracrine and autocrine factors. An invariable prerequisite for the development of uterine receptivity to implantation is continuous exposure of the endometrium to progesterone which, after a species-specific interval, downregulates progesterone receptor (PGR) expression in the epithelium and stimulates the production of progestamedins. Uterine receptivity involves temporal changes in the expression of genes, leading to modifications in surface, extracellular matrix and secretory characteristics that support growth, proliferation, migration and attachment of the conceptus. Moreover, a complex interplay between endometrial progestamedins and estramedins and conceptus-derived oestrogens, cytokines and interferons (INFs), prostaglandins (PGs) and cortisol is crucial to the preparation for implantation. Understanding the individual roles and combined actions of conceptus and endometrial autocrine and paracrine factors in the development of uterine receptivity to implantation is essential for translational research into strategies to reduce pregnancy loss in man and animals.