Factors involved in regulating trophoblast fusion: potential role in the development of preeclampsia.

In the human placenta, turnover of villous trophoblast involves proliferation, differentiation and fusion of mononucleated cytotrophoblasts with the overlying syncytiotrophoblast. In this way the syncytiotrophoblast is continuously supplied with compounds derived from the fusing cytotrophoblasts. Acquisition of fresh cellular components is balanced by a concomitant release of apoptotic material as syncytial knots from the syncytiotrophoblast to the maternal circulation. In the turnover of villous trophoblast, fusion is an essential step and has been shown to be regulated by multiple factors, such as cytokines, hormones, protein kinases, transcription factors, proteases and membrane proteins. Dysregulation of one or more of these fusion factors entails aberrant fusion of the cytotrophoblast with the syncytiotrophoblast, which adversely affects the maintenance and integrity of the placental barrier. Unbalanced trophoblast fusion and release of apoptotic material into the intervillous space may provoke a massive systemic inflammatory response by the mother and thus lead to preeclampsia.