DMT1 Maintains Iron Homeostasis to Regulate Mitochondrial Function in Porcine Oocytes

Iron plays critical roles in many cellular functions, including energy production, metabolism, and cell proliferation. However, the role of iron in maintaining oocyte quality remains unclear. In this study, DMT1 was identified as a key iron transporter during porcine oocyte maturation. The results demonstrated that iron deficiency in porcine oocyte led to aberrant meiotic progression, accompanied by increased gene expression of DMT1. Inhibition of DMT1 resulted in the failure of cumulus cell expansion and oocyte maturation, along by the abnormal actin and microtubule assembly. Furthermore, loss of DMT1 function caused disruption in mitochondrial function and dynamics, resulting in oxidative stress and Ca²⁺ dyshomeostasis. Additionally, the absence of DMT1 function activated PINK1/Parkin-dependent mitophagy in porcine oocyte. These findings suggested that DMT1 played a crucial role in safeguarding oocyte quality by protecting against iron-deficiency-induced mitochondrial dysfunction and autophagy. This study provided compelling evidence that DMT1 and iron homeostasis were crucial for maintaining the capacity of porcine oocyte maturation. Moreover, the results hinted at the potential of DMT1 as a novel therapeutic target for treating iron deficiency-related female reproductive disorders.