Mechanisms of endometrial control of trophoblast invasion

Tumour invasion and trophoblastic invasion share the same biochemical media tors: the matrix metalloproteinases (MMPs) and their inhibitors. MMPs are a family of enzymes capable of digesting the extracellular matrices of the h ost tissues. Human cytotrophoblastic cells are constitutively invasive and produce MMPs. Tissue inhibitors of metalloproteinases inhibit cytotrophobla stic invasion in vitro, indicating that MMPs are causally related to tropho blast invasion in the endometrium. Ln contrast to tumour invasion of a host tissue, trophoblastic invasion during implantation and placentation is con trolled stringently in both space and time. The factors responsible for the se important regulatory processes are unknown but studies in vitro indicate that endometrial cytokines and growth factors are possible candidates. Ins ulin-like growth factor binding protein 1, the major secretory product of t he decidua, interleukin 1, interleukin 6, leptin and tumour necrosis factor alpha, all of endometrial origin, are stimulators of MMPs, whereas transfo rming growth factor beta inhibits the proteolytic activity of cytotrophobla stic cells. Unfortunately, the ways in which these individual factors inter act to regulate trophoblast invasion are far from being understood.