title: Thyroxine Exposure Effects on the Cranial Base.
abstract: Thyroid hormone is important for skull bone growth, which primarily occurs at the cranial sutures and synchondroses. Thyroid hormones regulate metabolism and act in all stages of cartilage and bone development and maintenance by interacting with growth hormone and regulating insulin-like growth factor. Aberrant thyroid hormone levels and exposure during development are exogenous factors that may exacerbate susceptibility to craniofacial abnormalities potentially through changes in growth at the synchondroses of the cranial base. To elucidate the direct effect of in utero therapeutic thyroxine exposure on the synchondroses in developing mice, we provided scaled doses of the thyroid replacement drug, levothyroxine, in drinking water to pregnant C57BL6 wild-type dams. The skulls of resulting pups were subjected to micro-computed tomography analysis revealing less bone volume relative to tissue volume in the synchondroses of mouse pups exposed in utero to levothyroxine. Histological assessment of the cranial base area indicated more active synchondroses as measured by metabolic factors including Igf1. The cranial base of the pups exposed to high levels of levothyroxine also contained more collagen fiber matrix and an increase in markers of bone formation. Such changes due to exposure to exogenous thyroid hormone may drive overall morphological changes. Thus, excess thyroid hormone exposure to the fetus during pregnancy may lead to altered craniofacial growth and increased risk of anomalies in offspring.
authors.affiliation: Department of Oral Health Sciences, Medical University of South Carolina, 173 Ashley Avenue, BS 230B, Charleston, SC, 29425, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Durham
authors.affiliation: Department of Oral Health Sciences, Medical University of South Carolina, 173 Ashley Avenue, BS 230B, Charleston, SC, 29425, USA.
authors.forename: R Nicole
authors.initials: RN
authors.lastname: Howie
authors.affiliation: Department of Oral Biology, School of Dental Medicine, Center for Craniofacial and Dental Genetics, University of Pittsburgh, 3501 Terrace Street, Pittsburgh, PA, 15213, USA.
authors.forename: Trish
authors.initials: T
authors.lastname: Parsons
authors.affiliation: Department of Oral Health Sciences, Medical University of South Carolina, 173 Ashley Avenue, BS 230B, Charleston, SC, 29425, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Bennfors
authors.affiliation: Department of Oral Health Sciences, Medical University of South Carolina, 173 Ashley Avenue, BS 230B, Charleston, SC, 29425, USA.
authors.forename: Laurel
authors.initials: L
authors.lastname: Black
authors.affiliation: Department of Oral Biology, School of Dental Medicine, Center for Craniofacial and Dental Genetics, University of Pittsburgh, 3501 Terrace Street, Pittsburgh, PA, 15213, USA.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Weinberg
authors.affiliation: Departments of Oral Biology, Cellular Biology and Anatomy, Orthopaedic Surgery and Oral and Maxillofacial Surgery, Augusta University, 1120 15th Street, Augusta, GA, 30912, USA.|Institute for Regenerative and Reparative Medicine, Augusta University, 1120 15th Street, Augusta, GA, 30912, USA.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Elsalanty
authors.affiliation: Institute for Regenerative and Reparative Medicine, Augusta University, 1120 15th Street, Augusta, GA, 30912, USA.|Division of Plastic Surgery, Department of Surgery, Augusta University, 1120 15th Street, Augusta, GA, 30912, USA.
authors.forename: Jack C
authors.initials: JC
authors.lastname: Yu
authors.affiliation: Department of Oral Health Sciences, Medical University of South Carolina, 173 Ashley Avenue, BS 230B, Charleston, SC, 29425, USA. crayj@musc.edu.
authors.forename: James J
authors.initials: JJ
authors.lastname: Cray
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology*; D019291:Skull Base / Q000187:drug effects* / Q000254:growth & development*; D013963:Thyroid Hormones / Q000633:toxicity; D013974:Thyroxine / Q000633:toxicity*; D055114:X-Ray Microtomography
chemical_list: D013963:Thyroid Hormones; D013974:Thyroxine
keywords: Cartilage; Collagen type; Cranial base; Craniofacial growth; Thyroid hormone