TCDD induces cleft palate through exosomes derived from mesenchymal cells

Abstract

Abstract TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is a ubiquitous environmental toxicant and a notable teratogenic agent for cleft palate (CP), a common congenital structural malformation that can result from abnormalities during palatal shelf connection and/or fusion. The development of the palate requires precise coordination between mesenchymal and epithelial cells. Exosomes are vesicles secreted by cells and participate in organ development by transferring various bioactive molecules between cells and regulating cell proliferation, migration, apoptosis, and epithelial–mesenchymal transition (EMT); these vesicles represent a new method of intercellular communication. To explore how TCDD could influence palatal cell behaviors and communication, we treated mesenchymal cells with TCDD, collected the exosomes secreted by the cells, assessed the 2 types of palatal cells, and then observed the effects of TCDD-induced exosomes. We found that the effects of TCDD-induced exosomes were equal to those of TCDD. Thus, TCDD might change the genetic materials of palatal cells and exosomes to cause dysregulated gene expression from parental cells, affect cellular information communicators, and induce abnormal cellular behaviors that could lead to CP.