Mechanisms of endometrial control of trophoblast invasion.
Tumour invasion and trophoblastic invasion share the same biochemical mediators: the matrix metalloproteinases (MMPs) and their inhibitors. MMPs are a family of enzymes capable of digesting the extracellular matrices of the host tissues. Human cytotrophoblastic cells are constitutively invasive and produce MMPs. Tissue inhibitors of metalloproteinases inhibit cytotrophoblastic invasion in vitro, indicating that MMPs are causally related to trophoblast invasion in the endometrium. In contrast to tumour invasion of a host tissue, trophoblastic invasion during implantation and placentation is controlled stringently in both space and time. The factors responsible for these important regulatory processes are unknown but studies in vitro indicate that endometrial cytokines and growth factors are possible candidates. Insulin-like growth factor binding protein 1, the major secretory product of the decidua, interleukin 1, interleukin 6, leptin and tumour necrosis factor alpha, all of endometrial origin, are stimulators of MMPs, whereas transforming growth factor beta inhibits the proteolytic activity of cytotrophoblastic cells. Unfortunately, the ways in which these individual factors interact to regulate trophoblast invasion are far from being understood.
Bischof
P
P
Department of Obstetrics and Gynaecology, Laboratoire d'Hormonologie, Geneva University Hospital, Switzerland.
Meisser
A
A
Campana
A
A
D000818:Animals; D010064:Embryo Implantation / Q000502:physiology*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D019899:Paracrine Communication / Q000502:physiology*; D011247:Pregnancy; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014327:Trophoblasts / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D006133:Growth Substances; D018970:Insulin-Like Growth Factor Binding Protein 1; D007375:Interleukin-1; D015850:Interleukin-6; D020738:Leptin; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases