2. Academic Validation
  3. Aflatoxin B1 impairs leydig cells through inhibiting AMPK/mTOR-mediated autophagy flux pathway

Aflatoxin B1 impairs leydig cells through inhibiting AMPK/mTOR-mediated autophagy flux pathway

  • Chemosphere. 2019 Oct;233:261-272. doi: 10.1016/j.chemosphere.2019.05.273.
Xianwu Chen 1,  Chao Li 2,  Yong Chen 2,  Chaobo Ni 2,  Xiuxiu Chen 2,  Linlei Zhang 2,  Xuni Xu 3,  Min Chen 3,  Xinyi Ma 3,  Huilu Zhan 3,  Aoyu Xu 3,  Renshan Ge 2,  Xiaoling Guo 4
Affiliations

Affiliations

  • 1 Center of Scientific Research, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 2 Center of Scientific Research, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 3 Center of Scientific Research, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; The Second Clinical Medical School of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 4 Center of Scientific Research, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; The Second Clinical Medical School of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: [email protected].
PMID: 31176127 DOI: 10.1016/j.chemosphere.2019.05.273
Abstract

Aflatoxin B1 (AFB1), a potential endocrine disrupter, has been shown to induce hepatotoxicity in animal models, but the effects of AFB1 on Leydig cell function are unclear. In this study, in vivo exposure to AFB1 at 15 and 150 μg/kg/day lowered serum testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels, reduced Leydig cell number, and down-regulated the expression of testosterone biosynthesis-related genes. In vitro study showed that AFB1 (10 μM) significantly increased ROS levels, and decreased T production in Leydig cells by suppressing certain T-biosynthesis gene expressions. Moreover, AFB1 induced Leydig cell Apoptosis through lowering pAMPK/AMPK ratio and increasing pmTOR/mTOR ratio, and then further up-regulating Autophagy and Apoptosis proteins, LC3, BECLIN 1, and Bax, as well as down-regulating Autophagy flux protein P62 and anti-apoptosis protein Bcl-2. AFB1-induced toxicity in Leydig cells was characterized by inhibiting T-biosynthesis gene expression, reducing Leydig cell number, promoting ROS production, and inducing cell Apoptosis via suppressing AMPK/mTOR-mediated Autophagy flux pathway.

Keywords

AMPK/mTOR-mediated autophagy flux; Aflatoxin B1; Apoptosis; Leydig cells; Testosterone.

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