A novel posttranslational modification of histone, H3 S-sulfhydration, is down-regulated in asthenozoospermic sperm

作者：Qi Qi, Hongjie Pan, Ning Jiang, Meixin Zhang, Shenfei Sun, Xiaofeng Wan, Fangxi Zhang, Lingling Zhang, Hua Diao, Jian Wang, Li R · 发表于：Journal of Assisted Reproduction and Genetics · 年份：2021 · DOI：10.1007/s10815-021-02314-x · 被引用次数：16 · 研究领域：Sulfur Compounds in Biology、Sperm and Testicular Function、Selenium in Biological Systems

S) has been widely recognized to be a potent antioxidant whose role is partially implemented by protein S-sulfhydration. However, protein S-sulfhydration has not been reported in germ cells. Therefore, we investigated whether asthenozoospermia could be associated with sperm protein S-sulfhydration. S-sulfhydrated proteins in human sperm were enriched via biotin-switch assay and analyzed using LC-MS/MS spectrometry. Two hundred forty-four S-sulfhydrated proteins were identified. Importantly, we validated that sperm histones H3.1 and H3.3 were the S-sulfhydrated proteins. Their S-sulfhydrated amino acid residue was Cysteine111. Abundances of S-sulfhydrated H3 (sH3) and S-sulfhydrated H3.3 (sH3.3) were significantly down-regulated in asthenozoospermic sperm, compared with the fertile controls, and were significantly correlated with progressive motility. Retinoic acid (RA) up-regulated level of sH3.3 in primary round spermatids and the C18-4 cells (a mouse spermatogonial stem cell line). Overexpression of the mutant H3.3 (Cysteine111 was replaced with serine) affected expression of 759 genes and raised growth rate of C18-4 cells. For the first time, S-sulfhydration H3 and H3.3 were demonstrated in the present study. Our results highlight that aberrant S-sulfhydration of H3 is a new pathophysiological basis in male infertility.