A PDMS-Based Interdigitated Platform for Trophoblast Invasion Study Under Oxygen Stress Conditions

In human pregnancy, successful invasion/migration of trophoblast cells under controlled oxygen pressure regulates the fetus development, while a defective invasion leads to obstetric complications including miscarriage, pre-eclampsia, placenta abruption, and intrauterine death. However, the underlying mechanism of defective cell invasion by hypoxia is still unknown. Conventional systems employed to study this cell invasion/migration have several limitations such as non-tunability, and absence of physiological conditions. Herein, we reported a polydimethylsiloxane (PDMS) based simple interdigitated disk platform to study the cell invasion/migration under hypoxic (0.5% O2) and normoxic (21% O2) conditions. Human trophoblast cells (HTR-8/SVneo) and human umbilical vein endothelial cells (HUVEC) were seeded on the interdigitated disk separated by an extracellular matrix (ECM) layer. The trophoblast invasion to the HUVEC side was analyzed and compared under both hypoxic and normoxic conditions. Furthermore, the secretion of biological factors, hypoxic induced factor 1-alpha (HIF-1α), and matrix metalloproteinase (MMP) -2 and 9, involved in trophoblast invasion were also analyzed using western blot and zymography. The results showed that under long-term exposure to a hypoxic environment, cells secrete a high amount of MMP-9, which is responsible for ECM breakdown and enhanced trophoblast invasion. Hence, the long-term hypoxic exposure improves the invasion mechanism of trophoblast. Therefore, we suggest that a PDMS-based interdigitated device could be a useful tool to understand the mechanisms of cell-to-cell interaction as well as the invasion of trophoblast by oxygen pressure.