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Low acrosin activity is associated with decreased Spam1/acrosin expression and GSH deficiency-caused premature acrosome release of human sperm cells

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Abstract

Low acrosin activity (LAA) is associated with sperm function anomaly and poor outcomes of in vitro fertilization. In this study, we confirm that 993 semen samples with LAA had a reduced sperm motility and low in vitro fertilization rate in comparison with 1332 normal controls (NC). Proteomic comparison between 11 LAA and 11 NC sperm samples identified 35 upregulated and 99 downregulated proteins in the LAA group. Indeed, proteomic data showed that acrosome enzymes Spam1 and Acrosin were among the downregulated proteins in the LAA group, which was validated by quantitative PCR and immunefluorescent staining of sperm cells. The KEEG pathway analysis revealed a deficiency of GSH and Gln biosynthesis in LAA sperm cells. Immunofluorescent staining of sperms and quantitative PCR verified downregulation of GLUL and GCLC, the key enzymes for GSH and Gln biosynthesis. Moreover, the results of ELISA assay confirmed low levels of GSH and Gln in LAA sperm cells. Mechanistic studies showed that addition of 10 mM H2O2 to semen samples led to a significant reduction of acrosin activity and sperm motility, most possibly by triggering premature acrosome release. In contrast, the presence of 20 mM GSH blocked the oxidative effects of H2O2. Since GSH counteracts the oxidative stress and Gln participates in TCA cycling, their deficiency may affect the redox balance as well as energy production of sperm cells. These findings shed new light on the pathological mechanisms of infertility associated with LAA. Male infertility patients could benefit from GSH supplement by improvement of acrosin activity and other sperm functions.

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Acknowledgements

The authors thank the patients participated in this study and the physicians/technicians contributed to the study.

Funding

This work was supported by the Shuangchuang Program of Jiangsu Province (Shi-Wen Jiang); the Wuxi Leading Talents in Medical and Health Profession Program (Shi-Wen Jiang); the Fenghuanchao Program (Shi-Wen Jiang) of the Wuxi Taihu Lake Talent Plan; and research funding from Lianyungang Maternal and Child Health Hospital.

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Authors and Affiliations

  1. Center of Reproductive Medicine, Women’s Hospital of Jiangnan University, Wuxi, Jiangsu, 214002, China

    Mengyuan Lin

  2. State Key Laboratory of Reproductive Medicine, Research Institute for Reproductive Health and Genetic Diseases, Women’s Hospital of Jiangnan University, Wuxi, Jiangsu, 214002, China

    Pengyun Ling, Daozhen Chen & Shi-Wen Jiang

  3. Department of Public Health, Women’s Hospital of Jiangnan University, Wuxi, Jiangsu, 214002, China

    Qingwen He

  4. Women’s Hospital of Jiangnan University, Wuxi, Jiangsu, 214002, China

    Daozhen Chen

  5. Haidong Second People’s Hospital, Haidong, Qinghai, 810700, China

    Daozhen Chen

  6. Lianyungang Research Institute for Women’s and Children’s Health, Lianyungang Maternal and Child Health Hospital, Lianyungang, Jiangsu, China

    Lianshuai Zheng & Shi-Wen Jiang

  7. Clinical Center of Reproductive Medicine, Lianyungang Maternal and Child Health Hospital, Lianyungang, Jiangsu, China

    Lisha Tang

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  1. Mengyuan Lin
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Correspondence to Lisha Tang or Shi-Wen Jiang.

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Ethical approval and informed consent

This retrospective study was approved by the Ethics Committee of Women’s Hospital of Jiangnan University (No:2021-01-0927-27), and written informed consent was signed by all study subjects. All procedures involving human participants were carried out per institutional and national ethical standards as well as the 1964 Helsinki declaration and its later amendments.

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Lin, M., Ling, P., He, Q. et al. Low acrosin activity is associated with decreased Spam1/acrosin expression and GSH deficiency-caused premature acrosome release of human sperm cells. Cell Tissue Res 394, 529–545 (2023). https://doi.org/10.1007/s00441-023-03826-x

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  • DOI: https://doi.org/10.1007/s00441-023-03826-x

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