Copper overload exacerbates testicular aging mediated by lncRNA:CR43306 deficiency through ferroptosis in Drosophila
Qiuru Huang,
Jiaxin Li,
Yujuan Qi,
Xuxin He,
Cong Shen,
Chenyu Wang,
Xinda Wang,
Qiushi Xia,
Yi Zhang,
Ziyue Pan,
Qingqing Hu,
Ziyu Cao,
Yiheng Liu,
Jingqi Huang,
Guoqing Han,
Ying Zheng,
Bo Zheng,
Xuhui Zeng,
Xiaolin Bi,
Jun Yu
Affiliations
Qiuru Huang
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China
Jiaxin Li
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China
Yujuan Qi
Clinical Center of Reproductive Medicine, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, 221000, China
Xuxin He
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China
Cong Shen
State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproduction and Genetics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, 215002, China
Chenyu Wang
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China
Xinda Wang
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China
Qiushi Xia
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China
Yi Zhang
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China
Ziyue Pan
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China
Qingqing Hu
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China
Ziyu Cao
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China
Yiheng Liu
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China
Jingqi Huang
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China
Guoqing Han
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China
Ying Zheng
Department of Histology and Embryology, School of Medicine, Yangzhou University, Yangzhou, 225009, China
Bo Zheng
State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproduction and Genetics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, 215002, China; Corresponding author.
Xuhui Zeng
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China; Corresponding authors.
Xiaolin Bi
School of Medicine, Nantong University, Nantong, 226001, China; Corresponding author.
Jun Yu
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China; Corresponding authors.
Testicular aging manifests as impaired spermatogenesis and morphological alterations in Drosophila. Nonetheless, the comprehensive molecular regulatory framework remains largely undisclosed. This investigation illustrates the impact of copper overload on testicular aging and underscores the interplay between copper overload and lncRNA. Copper overload triggers Cuproptosis through the mitochondrial TCA cycle, facilitating intracellular interactions with Ferroptosis, thereby governing testicular aging. Dysfunction of lncRNA:CR43306 also contributes to testicular aging in Drosophila, emphasizing the significance of lncRNA:CR43306 as a novel aging-associated lncRNA. Moreover, copper overload exacerbates spermatid differentiation defects mediated by lncRNA:CR43306 deficiency through oxidative stress, copper, and iron transport. Therapeutically, Ferrostatin-1 and Resveratrol emerge as potential remedies for addressing testicular aging. This study offers perspectives on the regulatory mechanisms involving copper overload and lncRNA:CR43306 deficiency in the context of testicular aging.
