Master's Course Student Konkuk University, Republic of Korea
Abstract: Bisphenol A (BPA), a widely encountered environmental endocrine disruptor, has been reported to affect embryonic development and implantation. However, the effect of BPA on embryogenesis and implantation has not been thoroughly investigated, primarily due to limitations in embryo availability and challenges with in vitro implantation systems. Here, we aimed to develop a novel system for toxicity testing using blastoids, which are derived from mouse induced pluripotent stem cells (iPSCs). To generate totipotent embryos containing both embryonic and extraembryonic cells, iPSCs were transitioned into a chemically induced totipotent stem cell (ciTotiSC) state. The resulting ciToti-blastoids resemble mouse blastocysts and exhibit proper lineage segregation, including the inner cell mass (ICM) and trophectoderm (TE), during blastoid formation. Exposure to BPA disrupted iPSC aggregation and reduced blastoid formation rates in a dose-dependent manner. Notably, the addition of glutathione, an antioxidant, rescued the detrimental effects of BPA on blastoid formation, suggesting that BPA-induced reactive oxygen species (ROS) generation underlies its toxicity, which can be mitigated by glutathione. Furthermore, glutathione-supplemented medium extended the maintenance of blastoids, highlighting its role in promoting blastoid stability and viability. These findings indicated that the established ciToti-blastoids system can be a reliable platform for studying the impact of environmental toxins such as BPA.
