PhD Student The University of Hong Kong, Hong Kong
Abstract: Successful trophoblast differentiation is essential for proper embryo implantation and placental development. However, as restricted by the ethical concerns of acquiring early human embryo samples, the exact molecular pathways of early human trophoblast development remain poorly understood. Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear receptor widely recognized for its transcriptional roles to regulate various metabolism and stem cell differentiation. Although previous human and transgenic mouse studies have reported that PPARγ-mediated signaling is crucial for normal placental and embryo development, the dynamic expression and precise functional effects of PPARγ during early trophoblast differentiation in human have yet to be elucidated. In this study, we employed human expanded potential stem cell (hEPSC)-derived trophoblastic cells and the hEPSC-derived early trophoblastic spheroid to explore the detailed molecular roles of PPARγ during early trophoblast differentiation. The study has initially confirmed a progressive increase in PPARγ mRNA levels during induced trophoblast differentiation. Treatment of PPARγ agonist L-165041 enhanced extravillous trophoblast differentiation with enhanced matrix metalloproteinase-2 (MMP2) secretion while the antagonist T0070907 significantly inhibited syncytiotrophoblast differentiation with reduction in Human chorionic gonadotropin secretion. To further validate the functional effects of PPARγ, the study has conducted functional assays on the modulated trophoblastic cells. The results showed that L-165041 induced invasive ability of trophoblast cells and enhanced attachment ability of BAP-EB onto endometrial cell lines, suggesting the critical roles of PPARγ-mediated signaling on trophoblast differentiation and its involvement in normal implantation processes. Collectively, these findings have advanced our understanding of the roles of PPARγ in early trophoblast differentiation and potentially broadened our knowledge of the molecular mechanisms regulating early implantation in human trophoblasts in general.
