{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T08:07:12Z","timestamp":1783843632384,"version":"3.55.0"},"reference-count":56,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T00:00:00Z","timestamp":1757721600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T00:00:00Z","timestamp":1757721600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["anatomypubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Thyroid hormones (TH) play critical roles in embryonic vascular development, yet their precise molecular contributions remain inadequately defined. This study investigates how pharmacological blockade of thyroid hormone receptors (TR) by amiodarone disrupts angiogenesis and associated molecular signaling pathways in chick embryos.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Amiodarone\u2010treated embryos exhibited notable morphological defects, including hematomas, anophthalmia, ventral wall defects, and limb anomalies, primarily affecting lateral plate mesoderm\u2010derived tissues. Chorioallantoic membrane analysis revealed significant reductions in vessel density, branching, and total vessel length, along with increased lacunarity, indicating impaired angiogenesis. Molecular profiling showed consistent down\u2010regulation of key angiogenic regulators such as\n                      <jats:italic>VEGF\u03b1<\/jats:italic>\n                      ,\n                      <jats:italic>WNT7A<\/jats:italic>\n                      ,\n                      <jats:italic>BMP2\/6<\/jats:italic>\n                      , and phosphatidylinositol 3\u2010kinase\/ Ak strain transforming (\n                      <jats:italic>PI3K\/AKT)<\/jats:italic>\n                      at both transcript and protein levels. In silico docking confirmed strong TR\u03b1 and TR\u03b2 binding, while deiodinase activity assays and western blotting demonstrated impaired thyroxine\u2010to\u2010triiodothyronine (T3) conversion and reduced T3 levels, confirming systemic hypothyroidism and disrupted thyroid hormone signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings underscore the essential role of thyroid hormone signaling in embryonic angiogenesis. Disruption of TR activation by amiodarone significantly impairs vascular formation through coordinated suppression of Vascular endothelial growth factor alpha (VEGF\u03b1), WNT7A, bone morphogenetic proteins, and PI3K\/AKT pathways. These insights enhance our understanding of TH\u2010related developmental disorders and may guide therapeutic strategies for managing vascular dysfunctions associated with impaired thyroid signaling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/dvdy.70076","type":"journal-article","created":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T10:14:38Z","timestamp":1757758478000},"page":"698-723","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Thyroid hormone receptor blockade by amiodarone disrupts angiogenesis via\n                    <scp>VEGF\u03b1<\/scp>\n                    ,\n                    <scp>WNT7A<\/scp>\n                    ,\n                    <scp>BMP<\/scp>\n                    , and\n                    <scp>PI3K<\/scp>\n                    \/\n                    <scp>AKT<\/scp>\n                    pathways in chick embryo vascular 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