BDE-47 Induces Mitochondrial Dysfunction and Endoplasmic Reticulum Stress to Inhibit Early Porcine Embryonic Development

Simple Summary The 2,2 & PRIME;4,4 & PRIME;-tetrabromodiphenyl ether (BDE-47) is a common flame retardant that can be widely distributed in the environment and organisms but has been shown to induce toxicity to various organisms and organ systems. We found that exposure to BDE-47 induced the early embryonic development of in vitro porcine culture through oxidative stress and autophagy induced by mitochondrial dysfunction and endoplasmic reticulum stress. Widely used as a flame retardant, 2,2 & PRIME;4,4 & PRIME;-tetrabromodiphenyl ether (BDE-47) is a persistent environmental pollutant with toxicological effects, including hepatotoxicity, neurotoxicity, reproductive toxicity, and endocrine disruption. To investigate the toxicological effects of BDE-47 on early porcine embryogenesis in vitro, cultured porcine embryos were exposed to BDE-47 during early development. Exposure to 100 & mu;M BDE-47 decreased the blastocyst rate and mRNA level of pluripotency genes but increased the level of LC3 and the expression of autophagy-related genes. After BDE-47 exposure, porcine embryos' antioxidant capability decreased; ROS levels increased, while glutathione (GSH) levels and the expression of antioxidant-related genes decreased. In addition, BDE-47 exposure reduced mitochondrial abundance and mitochondrial membrane potential levels, downregulated mitochondrial biogenesis-associated genes, decreased endoplasmic reticulum (ER) abundance, increased the levels of GRP78, a marker of ER stress (ERS), and upregulated the expression of ERS-related genes. However, ER damage and low embryo quality induced by BDE-47 exposure were reversed with the ERS inhibitor, the 4-phenylbutyric acid. In conclusion, BDE-47 inhibits the development of early porcine embryos in vitro by inducing mitochondrial dysfunction and ERS. This study sheds light on the mechanisms of BDE-47-induced embryonic toxicity.