Zhang Jin-Xin, Lan Meng-Fan, Shang Jian-Zhou, Lai Xin-Le, Li Li-Shu, Duan Tong-Tong, Xu Ru-Hai, Chen Kun-Lin, Duan Xing
College of Animal Science and Technology & College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, Zhejiang, China.
Key Laboratory of Animal Genetics and Breeding of Zhejiang Province, Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Sciences, Hangzhou, China.
J Cell Physiol. 2025 Jan;240(1):e31494. doi: 10.1002/jcp.31494. Epub 2024 Dec 5.
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 Ca 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.
铁在许多细胞功能中发挥着关键作用,包括能量产生、新陈代谢和细胞增殖。然而,铁在维持卵母细胞质量方面的作用仍不清楚。在本研究中,DMT1被确定为猪卵母细胞成熟过程中的关键铁转运蛋白。结果表明,猪卵母细胞缺铁导致减数分裂进程异常,同时DMT1基因表达增加。抑制DMT1会导致卵丘细胞扩展和卵母细胞成熟失败,并伴有肌动蛋白和微管组装异常。此外,DMT1功能丧失会导致线粒体功能和动态变化紊乱,从而导致氧化应激和钙稳态失调。此外,DMT1功能缺失会激活猪卵母细胞中PINK1/ Parkin依赖性线粒体自噬。这些发现表明,DMT1通过防止缺铁诱导的线粒体功能障碍和自噬,在保护卵母细胞质量方面发挥着关键作用。本研究提供了令人信服的证据,表明DMT1和铁稳态对于维持猪卵母细胞成熟能力至关重要。此外,研究结果还暗示了DMT1作为治疗缺铁相关女性生殖障碍的新型治疗靶点的潜力。