A Preliminary Study of the Relationship Between Zinc and the AhR Signaling Pathway During Palatal Development.

Abstract

ObjectiveTo investigate the effects of zinc concentration on palatal development in fetal mice and its association with the aryl hydrocarbon receptor (AhR) signaling pathway.MethodsPregnant C57BL/6J mice were fed diets with varying zinc concentrations and randomly divided into a zinc-rich (ZR) group, a normal-zinc (NZ) group, and a zinc-deficient (ZD) group. Embryonic development was observed, and the expression levels of AhR signaling pathway-related factors were examined.ResultsNo cleft palate was observed in the ZR group or NZ group, whereas the zinc-deficient group exhibited a cleft palate incidence of 27.45%. Hematoxylin and Eosin (HE) staining results revealed failed palatal shelf contact and fusion in the ZD group, whereas complete fusion occurred in the ZR group and a normal medial edge epithelial formed in the NZ group. Results from Immunohistochemistry (IHC), qRT-PCR, and Western blot analyses collectively demonstrated that, compared to the NZ group, the ZR group exhibited significant upregulation (P < .05) in both mRNA and protein expression levels of AhR, HSP90, CYP1A1, and SP1, whereas the ZD group displayed significant downregulation (P < .05).ConclusionZinc concentration is intimately correlated with fetal mouse palatal development, where zinc deficiency may contribute to cleft palate formation through suppression of AhR signaling pathway, whereas zinc-rich conditions facilitate activation of this pathway. This study reveals the regulatory role of zinc-AhR signaling axis in palatal development through mouse models, offering novel theoretical insights into zinc deficiency-induced cleft palate pathogenesis and establishing a foundational framework for preventive interventions.