Cytokines, growth factors and macromolecules as mediators of implantation in mammalian species

Abstract

Implantation is one of the most critical steps in mammalian reproduction and implantation failure constitutes a major cause of infertility in both animals and humans. The mechanism of implantation is exclusively under the control of ovarian steroids progesterone and oestrogen whose actions are mediated in a complex phenomenon that involves a number of cytokines and growth factors. According to a plethora of literature on implantation in mammalian species, prominent of these cytokines and growth factor playing crucial roles in implantation include integrin, osteopontin, integrin, insulin-like growth factor and leukaemia inhibitory factor. Others are cluster domain 44, hyaluronan system and many non-adhesive molecules such as glycoprotein mucin 1. In this review, the specific roles played by these molecules are expatiated. Generally, they function as adhesive molecules that facilitate attachment of ligands/proteins on the trophectoderm to their respective receptors on endometrial luminal epithelia or vice versa. Sometimes, they also function as signalling molecules that enhance communication between implanting blastocyst and receptive endometrium. This is of particular importance in embryo culture and embryo transfer where in vitro derived blastocyst unlike the in vivo condition, is not exposed to these substances and hence, their absence may be partly responsible for the low implantation rate observed in the surrogate. Appreciation of the roles played by these cytokines, growth factors and molecules as revealed in this review will spur further research on these topics, facilitate their inclusion in embryo culture media (if positively required) and are considered as vital aspect while developing strategies to improve fertility.

Keywords: Hyaluronan; Implantation; Integrin; Mucin; Osteopontin.

Fig. 1

Proposed Interactions between trophectoderm of implantation-competent blastocyst and luminal epithelial cells of receptive endometrium mediated by implantation-related cytokines and growth factors in mouse model. During implantation, there is increase in expression of cytokines and growth factor such ITG, OPN, LIF, IGF, HA and CD44 at endometrium, while MUC1 is proposed to reduce at implantation site of endometrial LE in response to embryo signal. ITG is also produced by the blastocyst and OPN being a receptor for ITG binds to OPN on the endometrium to establish attachment with OPN on the trophoblast leading to adhesion of the luminal epithelia and trophectoderm. Legends: CD44; cluster domain 44, GE; glandular epithelia, HA; hyaluronan, IGF; insulin-like growth factor, ITG; integrin, LIF; leukaemia inhibitory factor, LE; luminal epithelium, MUC1; mucin, OPN; osteopontin.