Regulation of trophoblast differentiation during embryo implantation and placentation: Implications in pregnancy complications

A significant proportion of pregnancy related complications like preterm birth, preeclampsia, intra-uterine growth restriction (IUGR) and spontaneous abortion may be due to defects at various stages of embryo implantation process, in particular, placentation. One of these defects is impaired syncytialization. This may also be responsible for low success rate of embryo implantation during Assisted Reproductive Technology (ART). As it is an early differentiation event of the trophectoderm, unveiling its elementary molecular network might help in understanding the cause behind such complications and even ameliorate the success rate of pregnancies. Therefore, the current review highlights the available information with respect to effector molecules such as syncytins, syndecan-1, CD98, connexin-43, proteases and protease convertase in trophoblast syncytialization. Promotion of syncytialization by EGF, hCG, IGFs, LIF etc. and its inhibition by TGF-β1 and TNF-α is also discussed. The signaling pathways, such as PKA-CREB, MAPK, STAT, Wnt/β-catenin etc. through which various factors modulate the process of syncytialization have also been presented. Post-transcriptional regulation via microRNAs has also been discussed. The information provided in this review will help in our understanding of the molecular mechanisms associated with syncytialization and their implications in pregnancy related complications.