Modulation of estrogen causes disruption of craniofacial chondrogenesis in Danio rerio

Abstract

Estrogen is a steroid hormone that is ubiquitous in vertebrates, but its role in cartilage formation has not been extensively studied. Abnormalities of craniofacial cartilage and bone account for a large portion of birth defects in the United States. Zebrafish (Danio rerio) have been used as models of human disease, and their transparency in the embryonic period affords additional advantages in studying craniofacial development. In this study, zebrafish embryos were treated with 17-β estradiol (E2) or with an aromatase inhibitor and observed for defects in craniofacial cartilage. Concentrations of E2 greater than 2μM caused major disruptions in cartilage formation. Concentrations below 2μM caused subtle changed in cartilage morphology that were only revealed by measurement. The angles formed by cartilage elements in fish treated with 1.5 and 2μM E2 were increasingly wide, while the length of the primary anterior–posterior cartilage element in these fish decreased significantly from controls. These treatments resulted in fish with shorter, flatter faces as estrogen concentration increased. Inhibition of aromatase activity also resulted in similar craniofacial disruption indicating that careful control of estrogen signaling is required for appropriate development. Further investigation of the phenomena described in this study could lead to a better understanding of the etiology of craniofacial birth defects and endocrine disruption of cartilage formation.