Thyroid Hormone Deficiency Disrupts Embryonic Ventral Body Wall Development and Myogenesis With Partial Recovery Following LevothyroxineTherapy.

Background: Ventral body wall defects (VBWDs), including omphalocele and gastroschisis, result from failed embryonic midline closure and contribute to high neonatal morbidity. While thyroid hormones (THs) are essential for morphogenesis, their role in VBWD pathogenesis is not well defined.

Aim: To investigate the impact of TH deficiency on ventral body wall development in chick embryos and evaluate levothyroxine as a therapeutic intervention.

Materials And Methods: Hypothyroidism was induced on embryonic day 3 using thiourea (2.5 mg/50 μL), a thyroid peroxidase inhibitor. A rescue group received levothyroxine (2.5 μg/50 μL) on day 5.5. Embryos were harvested on days 6 and 10 for analysis of thyroid peroxidase activity, morphology, skeletal patterning, and expression of morphogenetic (SHH, MYOD, MSX1/2), epithelial/mesenchymal (CDH1/2, VIM, TGFβ1), and apoptotic (Cleaved CASPASE 3) markers.

Results: Thiourea-treated embryos exhibited incomplete ventral closure, skeletal abnormalities, impaired myogenesis, and disrupted epithelial-mesenchymal transition. Gene profiling showed downregulation of SHH, MYOD, and MSX1/2, with concomitant upregulation of CDH1, VIM, TGFβ1, and Cleaved CASPASE 3. Levothyroxine administration partially restored thyroid activity, improved wall integrity, and normalized developmental gene expression.

Discussion: TH deficiency perturbs morphogenetic signaling, leading to defective mesodermal differentiation, epithelial-mesenchymal imbalance, and enhanced apoptosis. Partial rescue with levothyroxine underscores the hormone's developmental role and therapeutic relevance.

Conclusion: TH insufficiency contributes to VBWDs by disrupting key pathways in myogenesis and tissue remodeling. Early levothyroxine supplementation may offer a strategy to mitigate endocrine-related congenital malformations.