Alterations in the expression of tissue specific genes of the developing mandible and heart in rat diabetic embryopathy
(English)Manuscript (preprint) (Other academic)
Background & Aim: Maternal diabetes induces skeletal and cardiac malformations in the offspring, both in human and experimental diabetic pregnancies. A developmental disturbance in neural crest cell (NCC) derived embryonic tissue is a plausible origin for these malformations. Thus, diabetes-exposed and control rat embryos from a locally outbred Sprague-Dawley rat strain were used to investigate tissue-specific alterations in the expression of suggested candidate genes in the developing mandible and heart anlage and in the whole embryo.
Methods: Female non-diabetic (N) and streptozotocin-induced manifestly diabetic (MD) rats were mated with N males. Embryos were collected and morphologically examined on gestational days (GD) 11 and 13. The developing mandible (first pharyngeal arch), heart anlage and the remaining embryonic tissues were prepared and analyzed with quantitative real time PCR.
Results: Maternal diabetes changed the gene expression in the developing mandible where Gpx1 (MD11) and Cat (MD13) decreased. In the heart anlage, diabetes decreased Nrf2 (MD11), whereas, in whole embryo, diabetes increased Nrf2 (MD13). Maternal diabetes changed the gene expression in the developing mandible, Bmp4 (MD13) decreased, and Gdnf (MD11 and MD13) and Ret (MD11 and MD13) increased. In the heart anlage, diabetes decreased Shh (MD11) and Gdnf (MD11 and MD13). In whole embryo, diabetes decreased Shh (MD11) and Gdnf (MD13) and increased Msx2 (MD13) and Ret (MD11 and MD13). Maternal diabetes changed the gene expression in the developing mandible; Pax3 was both increased (MD11) and decreased (MD13). In the heart anlage, diabetes decreased Pax3 (MD13), whereas, in the whole embryo, diabetes increased Pax3 (MD13) and both decreased p53 (MD11) and increased p53 (MD13).
Conclusions: Hyperglycemia in utero causes tissue-specific alterations in embryonic gene expression of several important antioxidative defense and developmental genes. Tissuespecific disturbance of gene expressions suggests a diminished ROS scavenging capacity and a role for altered gene expression of Gdnf, Ret, Bmp4 and Pax3 in the diabetes-induced embryonic dysmorphogenesis.
diabetes, malformations, teratogenic, gene expression
Cell and Molecular Biology
Research subject Medical Cell Biology
IdentifiersURN: urn:nbn:se:uu:diva-178168OAI: oai:DiVA.org:uu-178168DiVA: diva2:542210