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Scriptaid is a prospective agent for improving human asthenozoospermic sample quality and fertilization rate in vitro

Yang, Yi-Ting1,2,*; Yan, Bin3,*; Guo, Li-Na1; Liu, Miao3; Li, Yu-Hua1; Shao, Zhi-Yu4; Diao, Hua1; Liu, Su-Ying3; Yu, He-Guo1

1NHC Key Lab of Reproduction Regulation, Shanghai Engineering Research Center of Reproductive Health Drug and Devices, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai 200237, China

2School of Life Sciences and Technology, Tongji University, Shanghai 200092, China

3Reproductive Medicine Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China

4College of Chemistry and Chemical Engineering, Donghua University, Shanghai 201620, China

Correspondence: Dr. HG Yu (yuheguo@163.com) or Dr. SY Liu (liu.suying@zs-hospital.sh.cn)

Originally published: June 11, 2024 Received: September 28, 2023 Accepted: March 4, 2024


Male infertility is a global issue caused by poor sperm quality, particularly motility. Enhancement of the sperm quality may improve the fertilization rate in assisted reproductive technology (ART) treatment. Scriptaid, with a novel human sperm motility-stimulating activity, has been investigated as a prospective agent for improving sperm quality and fertilization rate in ART. We evaluated the effects of Scriptaid on asthenozoospermic (AZS) semen, including its impact on motility stimulation and protective effects on cryopreservation and duration of motility, by computer-aided sperm analysis (CASA). Sperm quality improvement by Scriptaid was characterized by increased hyaluronan-binding activity, tyrosine phosphorylation, adenosine triphosphate (ATP) concentration, mitochondrial membrane potential, and an ameliorated AZS fertilization rate in clinical intracytoplasmic sperm injection (ICSI) experiments. Furthermore, our identification of active Scriptaid analogs and different metabolites induced by Scriptaid in spermatozoa lays a solid foundation for the future biomechanical exploration of sperm function. In summary, Scriptaid is a potential candidate for the treatment of male infertility in vitro as it improves sperm quality, prolongs sperm viability, and increases the fertilization rate.

Keywords: asthenozoospermia; HDAC6; ICSI; Scriptaid; sperm motility

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Asian Journal of Andrology CN 31-1795/R ISSN 1008-682X  Copyright © 2023  Shanghai Materia Medica, Chinese Academy of Sciences.  All rights reserved.