The placenta is involved in the transport and exchange of gases, nutrients, and waste products at the mother-fetus interface. During the early stages of pregnancy, trophoblasts, the primary stem cell lineage in the placenta, play a crucial role in embryo implantation and in spiral artery remodeling. Improper progression of these initial stages can lead to various adverse effects for both mother and fetus. At a cellular level, AMP-activated protein kinase (AMPK) contributes not only to the maintenance of cellular homeostasis, but also possibly to the regulation of cell invasion, an important step in spiral artery remodeling.
It is proposed that AMPK regulates extravillous trophoblast cell invasion.
Using a transwell invasion assay, we determined that Metformin and 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) – an AMPK activator– increase trophoblast invasion. Conversely, Compound C, an AMPK inhibitor, decreases the cells’ ability to invade over a 32 hour period. Manipulation of AMPK expression via siRNA technology reduced trophoblast invasion across all of the pharmacological treatments. Altered expression of genes linked to trophoblast cell invasion, such as TIMP-1 .TIMP-2, MMP- 2 and MMP-9 were also observed.
AMPK was shown to play a role in altered trophoblast invasion through various invasion markers. Future steps include evaluating integrin expression, involved in cellular movement, to further elucidate this relationship.
Written By Guarrattan K. Chandhoke1, Patrick J.A. Rodriguez2, Anson Cheung1 & Sandeep Raha1,2
1Department of Pediatrics, McMaster University
2The Graduate Program in Medical Sciences, McMaster University