histone acetylase inhibitor curcumin impairs mouse spermiogenesis–an in vitro study组蛋白乙酰基转移酶抑制剂姜黄素影响鼠标spermiogenesis-an体外研究.pdfVIP

Histone Acetylase Inhibitor Curcumin Impairs Mouse Spermiogenesis–An In Vitro Study Xiaoyu Xia1,2., Heng Cai1,2., Shixiao Qin1,2, Chen Xu1,2* 1 Department of Histology Embryology, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 2 Shanghai Key Laboratory of Reproductive Medicine, Shanghai, China Abstract In the previous study, we unraveled the unique ‘‘erasure strategy’’ during the mouse spermiogenesis. Chromatin associated proteins sequentially disassociated from the spermatid chromosome, which led to the termination of transcription in ¨ elongating spermatids. By this process, a relatively naıve paternal chromatin was generated, which might be essential for the zygotic development. We supposed the regulation of histone acetylation played an important role throughout this ‘‘erasure’’ process. In order to verify this hypothesis, we treated mouse spermatids in vitro by histone acetylase (HAT) inhibitor Curcumin. Our results showed an inhibiting effect of Curcumin on the growth of germ cell line in a dose- dependent manner. Accordingly, the apoptosis of primary haploid spermtids was increased by Curcumin treatment. As expected, the acetylated histone level was downregulated. Furthermore, we found the transcription in spermatids ceased in advance, the dynamics of chromatin associated factors was disturbed by Curcumin treatment. The regulation of histone acetylation should be one of the core reprogramming mechanisms during the spermiogenesis. The reproductive toxicity of Curcumin needs to be thoroughly investigated, which is crucial for its further clinical application. Citation: Xia