Zinc transporter ZIP12 maintains zinc homeostasis and protects spermatogonia from oxidative stress during spermatogenesis

作者：Xinye Zhu, Chengxuan Yu, Wangshu Wu, Lei Shi, Chenyi Jiang, Li Wang, Zhide Ding, Yue Liu · 发表于：Reproductive Biology and Endocrinology · 年份：2022 · DOI：10.1186/s12958-022-00893-7 · 被引用次数：36 · 研究领域：Trace Elements in Health、Sperm and Testicular Function、Selenium in Biological Systems

BACKGROUND: Overwhelming evidences suggest oxidative stress is a major cause of sperm dysfunction and male infertility. Zinc is an important non-enzymatic antioxidant with a wide range of biological functions and plays a significant role in preserving male fertility. Notably, zinc trafficking through the cellular and intracellular membrane is mediated by specific families of zinc transporters, i.e., SLC39s/ZIPs and SLC30s/ZnTs. However, their expression and function were rarely evaluated in the male germ cells. The aim of this study is to determine and characterize the crucial zinc transporter responsible for the maintenance of spermatogenesis. METHODS: The expression patterns of all 14 ZIP members were characterized in the mouse testis. qRT-PCR, immunoblot and immunohistochemistry analyses evaluated the ZIP12 gene and protein expression levels. The role of ZIP12 expression was evaluated in suppressing the sperm quality induced by exposure to an oxidative stress in a spermatogonia C18-4 cell line. Zip12 RNAi transfection was performed to determine if its downregulation altered cell viability and apoptosis in this cell line. An obese mouse model fed a high-fat-diet was employed to determine if there is a correlation between changes in the ZIP12 expression level and sperm quality. RESULTS: The ZIP12 mRNA and protein expression levels were higher than those of other ZIP family members in both the mouse testis and other tissues. Importantly, the ZIP12 expression levels were very ...