2. Academic Validation
  3. The rare-earth yttrium induces cell apoptosis and autophagy in the male reproductive system through ROS-Ca2+-CamkII/Ampk axis

The rare-earth yttrium induces cell apoptosis and autophagy in the male reproductive system through ROS-Ca2+-CamkII/Ampk axis

  • Ecotoxicol Environ Saf. 2023 Jul 20;263:115262. doi: 10.1016/j.ecoenv.2023.115262.
Fangpeng Hou 1,  Junyun Huang 2,  Furong Qing 3,  Tianfu Guo 4,  Sijia Ouyang 4,  Lu Xie 4,  Yechun Ding 5,  Jingge Yu 3,  Yanmin Li 6,  Xia Liu 5,  Tian-Sheng He 7,  Xiaona Fan 8,  Zhiping Liu 9
Affiliations

Affiliations

  • 1 Center for Immunology, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, Jiangxi 341000, China; The First School of Clinical Medicine, Gannan Medical University, Ganzhou, Jiangxi 341000, China.
  • 2 Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, China.
  • 3 Center for Immunology, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, Jiangxi 341000, China; School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi 341000, China.
  • 4 School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi 341000, China.
  • 5 College of Pharmacy, Gannan Medical University, Ganzhou, Jiangxi 341000, China.
  • 6 Department of Urology, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, China.
  • 7 School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi 341000, China. Electronic address: hets@gmu.edu.cn.
  • 8 College of Pharmacy, Gannan Medical University, Ganzhou, Jiangxi 341000, China. Electronic address: xn918@126.com.
  • 9 Center for Immunology, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, Jiangxi 341000, China; School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi 341000, China. Electronic address: Zhiping.Liu@gmu.edu.cn.
PMID: 37480693 DOI: 10.1016/j.ecoenv.2023.115262
Abstract

China has the world's largest reserves of rare earth elements (REEs), but widespread mining and application of REEs has led to an increased risk of potential pollution. Yttrium (Y), the first heavy REEs to be discovered, poses a substantial threat to human health. Unfortunately, little attention has been given to the impact of Y on human reproductive health. In this study, we investigated the toxic effects of YCl3 on mouse testes and four types of testicular cells, including Sertoli, Leydig, spermatogonial and spermatocyte cells. The results showed that YCl3 exposure causes substantial damage to mouse testes and induces Apoptosis and Autophagy, but not Pyroptosis or necrosis, in testicular cells. Genome-wide gene expression analysis revealed that YCl3 induced significant changes in gene expression, with Ca2+ and mitochondria-related genes being the most significantly altered. Mechanistically, YCl3 exposure induced mitochondrial dysfunction in testicular cells, triggering the overproduction of Reactive Oxygen Species (ROS) by impairing the Nrf2 pathway, regulating downstream Ho-1 target protein expression, and increasing Ca2+ levels to activate the CamkII/AMPK signaling pathway. Blocking ROS production or Ca2+ signaling significantly attenuates Apoptosis and Autophagy, while supplementation with Ca2+ reverses the suppression of Apoptosis and Autophagy by ROS blockade in testicular cells. Notably, Apoptosis and Autophagy induced by YCl3 treatment are independent of each other. Thus, our study suggests that YCl3 may impair the antioxidant stress signaling pathway and activate the calcium pathway through the ROS-Ca2+ axis, which promotes testicular cell Apoptosis and Autophagy independently, thus inducing testicular damage and impairing male reproductive function.

Keywords

Apoptosis; Autophagy; Calcium; Male reproductive system; ROS; Yttrium.

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