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Mechanisms of endometrial control of trophoblast invasion
P Bischof1, A Meisser, A Campana
1Department of Obstetrics and Gynaecology, Laboratoire d'Hormonologie, Geneva University Hospital, Switzerland.
Abstract:
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.
Insights
Matrix metalloproteinases (MMPs) mediate both tumour and trophoblast invasion. While MMPs are essential for trophoblast invasion, endometrial factors tightly regulate this process during pregnancy.
Area of Science:
- Reproductive Biology
- Cell Biology
- Biochemistry
Background:
- Tumour invasion and trophoblast invasion share biochemical mediators, specifically matrix metalloproteinases (MMPs) and their inhibitors.
- MMPs are enzymes that degrade extracellular matrix, facilitating tissue invasion by cells like human cytotrophoblasts.
- Trophoblast invasion is crucial for implantation and placentation but is tightly regulated in space and time, unlike tumour invasion.
Purpose of the Study:
- To investigate the role of matrix metalloproteinases (MMPs) and their inhibitors in trophoblast invasion.
- To identify endometrial factors that regulate trophoblast invasion during implantation and placentation.
- To understand the complex interactions between endometrial factors and MMPs in controlling trophoblast invasion.
Main Methods:
- In vitro studies examining the effects of tissue inhibitors of metalloproteinases on cytotrophoblastic invasion.
- Analysis of endometrial cytokines and growth factors as potential regulators of trophoblast invasion.
- Investigating the influence of specific factors like insulin-like growth factor binding protein 1, interleukins, leptin, TNF-alpha, and TGF-beta on MMP activity.
Main Results:
- Tissue inhibitors of metalloproteinases were shown to inhibit cytotrophoblastic invasion in vitro, confirming MMPs' causal role.
- Endometrial factors such as insulin-like growth factor binding protein 1, interleukin 1, interleukin 6, leptin, and tumour necrosis factor alpha stimulate MMPs.
- Transforming growth factor beta was identified as an inhibitor of cytotrophoblastic proteolytic activity.
Conclusions:
- Matrix metalloproteinases (MMPs) are critical mediators of trophoblast invasion, similar to their role in tumour invasion.
- Endometrial factors play a significant role in regulating trophoblast invasion, although their precise interactions remain unclear.
- Further research is needed to elucidate the complex interplay of these factors in controlling trophoblast invasion during pregnancy.