2. Academic Validation
  3. Enniatin B1 induces damage to Leydig cells via inhibition of the Nrf2/HO-1 and JAK/STAT3 signaling pathways

Enniatin B1 induces damage to Leydig cells via inhibition of the Nrf2/HO-1 and JAK/STAT3 signaling pathways

  • Ecotoxicol Environ Saf. 2024 Feb 21:273:116116. doi: 10.1016/j.ecoenv.2024.116116.
Hongping Shen 1,  Yili Cai 2,  Keqi Zhu 1,  Dong Wang 3,  Rui Yu 4,  Xueqin Chen 5
Affiliations

Affiliations

  • 1 Department of Traditional Chinese Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, China.
  • 2 Department of Acupuncture, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, China.
  • 3 Shanghai Houyu Medical Equiment Co., Ltd, China.
  • 4 Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Ningbo University, China. Electronic address: [email protected].
  • 5 Department of Traditional Chinese Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, China. Electronic address: [email protected].
PMID: 38387140 DOI: 10.1016/j.ecoenv.2024.116116
Abstract

Enniatin B1 (ENN B1) is a mycotoxin that can be found in various foods. However, whether ENN B1 is hazardous to the reproductive system is still elusive. Leydig cells are testosterone-generating cells that reside in the interstitial compartment between seminiferous tubules. Dysfunction of Leydig cells could result in male infertility. This study aimed to examine the toxicological effects of ENN B1 against TM3 Leydig cells. ENN B1 significantly inhibited cell viability in a dose-dependent manner. ENN B1 treatment also decreased the expression of functional genes in Leydig cells. Moreover, ENN B1 induced Leydig cells Apoptosis and oxidative stress. Mechanistically, ENN B1 leads to the upregulation of Bax and downregulation of Bcl-2 in Leydig cells. In addition, ENN B1 inhibited the Nrf2/HO-1 pathway, which is critical for the induction of oxidative stress. Additionally, ENN B1 treatment repressed the JAK/STAT3 signaling pathway in Leydig cells. Rescue experiments showed that activation of STAT3 resulted in alleviation of ENN B1-induced damage in Leydig cells. Collectively, our study demonstrated that ENN B1 induced Leydig cell dysfunction via multiple mechanisms.

Keywords

Apoptosis; Enniatin B1; JAK/STAT3; Leydig cells; Nrf2/HO-1; Oxidative stress.

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