The role of growth factors and cytokines during implantation: endocrine and paracrine interactions

Abstract

Implantation, a critical step for establishing pregnancy, requires molecular and cellular events resulting in uterine growth and differentiation, blastocyst adhesion, invasion, and placental formation. Successful implantation requires a receptive endometrium, a normal and functional embryo at the blastocyst stage, and a synchronized dialogue between maternal and embryonic tissues. In addition to the well-characterized role of sex steroids, the complexity of embryo implantation and placentation is exemplified by the number of cytokines and growth factors with demonstrated roles in these processes. Disturbances in the normal expression and action of these cytokines result in an absolute or partial failure of implantation and abnormal placental formation in mice and human. Members of the gp130 cytokine family, interleukin-11 (IL-11) and leukemia inhibitory factor, the transforming growth factor beta superfamily, the colony-stimulating factors, and the IL-1 and IL-15 systems are crucial molecules for a successful implantation. Chemokines are also important, both in recruiting specific cohorts of leukocytes to the implantation site and in trophoblast trafficking and differentiation. This review provides discussion of the embryonic and uterine factors that are involved in the process of implantation in autocrine, paracrine, and/or juxtacrine manners at the hormonal, cellular, and molecular levels.

Figures

Figure 1

Lineage differentiation during 8-cell to blastocyst transition and gene expression patterns during mouse blastocyst formation. Oct4 is expressed throughout the embryo before the late morula and crucial for the formation of inner cell mass. The expression of Nanog is induced in the inside cells of the late morula. Cdx2 is expressed in trophectoderm. Gata6 is expressed in the primitive endoderm of the late blastocyst. 2PN, two pronuclei.