Effects of an aryl hydrocarbon receptor ligand on human trophoblast cell development

How does activation of aryl hydrocarbon receptor (AHR) signaling affect human trophoblast cell development and differentiation? AHR activation alters gene expression without impairing the ability of trophoblast cells to maintain a stem cell state or differentiate into essential cell types, such as extravillous trophoblast (EVT) cells or syncytiotrophoblast (ST), while promoting the production of 2-methoxy estradiol (2ME), which may impact placental development. The placenta serves both as a nutrient delivery system and a protective barrier against environmental toxins. AHR signaling is known to mediate cellular responses to environmental pollutants, potentially affecting trophoblast cell function, but the specific impacts of AHR activation on these cells were not fully understood. This study utilized an in vitro model of human trophoblast stem (TS) cells to investigate the downstream effects of AHR activation. The study focused on both undifferentiated TS cells and cells undergoing differentiation. Human TS cells were used as a model system. Researchers examined the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in TS cells maintained in their stem state and in TS cells induced to differentiate into EVT cells or ST. The study assessed changes in gene expression, particularly focusing on CYP1A1 and CYP1B1, as well as the production of 2ME. AHR activation stimulated the expression of CYP1A1 and CYP1B1, key genes associated with AHR signaling, in both undifferentiated and differentiating trophoblast cells. While AHR activation did not impact the ability of the cell to remain in a stem state or differentiate, it increased the production of 2ME, which may influence placentation. These effects were dependent on AHR signaling. n/a. This study was conducted in vitro, which may not fully replicate in vivo conditions. Further research is needed to confirm whether these findings apply to placental development in humans. The results suggest that AHR signaling activated by environmental pollutants could have a significant impact on placental development through mechanisms involving AHR activation. These findings may have broader implications for understanding how environmental factors affect fetal development. This work was funded by the National Institutes of Health: ES028957, HD020676, ES029280, HD105734, HD112559, and the Sosland Foundation. The authors declare no conflicts of interest.