Department of Traditional Chinese Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, China.
Department of Acupuncture, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, China.
Ecotoxicol Environ Saf. 2024 Mar 15;273:116116. doi: 10.1016/j.ecoenv.2024.116116. Epub 2024 Feb 21.
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.
恩镰孢菌素 B1（ENN B1）是一种存在于各种食物中的真菌毒素。然而，ENN B1 是否对生殖系统有害仍不得而知。睾丸间质细胞是位于生精小管之间的间质腔中的产生睾酮的细胞。睾丸间质细胞功能障碍可导致男性不育。本研究旨在研究 ENN B1 对 TM3 睾丸间质细胞的毒性作用。ENN B1 呈剂量依赖性显著抑制细胞活力。ENN B1 处理还降低了睾丸间质细胞中功能性基因的表达。此外，ENN B1 诱导睾丸间质细胞凋亡和氧化应激。在机制上，ENN B1 导致睾丸间质细胞中 Bax 的上调和 Bcl-2 的下调。此外，ENN B1 抑制了 Nrf2/HO-1 通路，该通路对于诱导氧化应激至关重要。此外，ENN B1 处理抑制了睾丸间质细胞中的 JAK/STAT3 信号通路。挽救实验表明，STAT3 的激活导致 ENN B1 诱导的睾丸间质细胞损伤减轻。总之，我们的研究表明，ENN B1 通过多种机制诱导睾丸间质细胞功能障碍。
