Timing of Secondary Palate Fusion in Human Embryos and Fetuses

INTRODUCTION: The human face develops through a complex sequence of growth and fusion events involving multiple pharyngeal arch derivatives. Disruptions in these processes can result in congenital anomalies such as cleft lip and/or palate (CL/P), which occur in approximately 1.6 per 1000 live births in Europe. Patients with CL/P often experience difficulties regarding feeding and speech, and studies suggest an increased risk of psychosocial difficulties. Understanding the morphological development and timing of secondary palate formation is essential for clarifying the pathogenesis of CL/P and identifying critical developmental periods during pregnancy. In this study, we aimed to evaluate the timing and morphological changes of the secondary palate in human embryos between Carnegie Stages 17-23 and fetuses aged 9-11 weeks post-conception (PC). METHODS: Histological sections and micro-CT scans of 26 human specimens, evenly distributed across these developmental stages, were analyzed. RESULTS: The results showed that palatal shelves first appear at CS18 and continue vertical outgrowth until CS22. At CS22, the shelves start to reorient horizontally and further extend medially. Shelf contact is observed at CS23, marking the onset of fusion, which is completed during or after 9 weeks PC. CONCLUSIONS: These findings refine the timeline of human secondary palate development. Importantly, identifying this critical developmental window suggests that current guidelines for administering medications during early pregnancy should be reevaluated, as drug exposure during this sensitive period may increase the risk of palatal malformations.