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Modeling methods for busulfan-induced oligospermia and asthenozoospermia in mice: a systematic review and meta-analysis

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Abstract

Objective

Modeling methods for busulfan-induced oligoasthenozoospermia are controversial. We aimed to systematically review the modeling method of busulfan-induced oligospermia and asthenozoospermia, and analyze changes in various evaluation indicators at different busulfan doses over time.

Methods

We searched the Cochrane Library, PubMed databases, Web of Science, the Chinese National Knowledge Infrastructure, and the Chinese Biomedical Literature Service System until April 9, 2022. Animal experiments of busulfan-induced spermatogenesis dysfunction were included and screened. The model mortality and parameters of the evaluation indicators were subjected to meta-analysis.

Results

Twenty-nine animal studies were included (control/model: 669/1829). The mortality of mice increased with busulfan dose. Significant spermatogenesis impairment occurred within 5 weeks, regardless of busulfan dose (10–40 mg/kg). Testicular weight (weighted mean difference [WMD]: − 0.04, 95% CI: − 0.05, − 0.03), testicular index (WMD: − 2.10, 95% CI: − 2.43, − 1.76), and Johnsen score (WMD: − 4.67, 95% CI: − 5.99, − 3.35) were significantly decreased. The pooled sperm counts of the model group were reduced by 32.8 × 106/ml (WMD: − 32.8, 95% CI: − 44.34, − 21.28), and sperm motility decreased by 37% (WMD: − 0.37, 95% CI: − 0.47, − 0.27). Sperm counts decreased slightly (WMD: − 3.03, 95% CI: − 3.42, − 2.64) in an intratesticular injection of low-dose busulfan (4 − 6 mg/kg), and the model almost returned to normal after one seminiferous cycle.

Conclusion

The model using low-dose busulfan (10 − 20 mg/kg) returned to normal after 10 − 15 weeks. However, in some spermatogenesis cycles, testicular weight reduction and testicular spermatogenic function damage were not proportional to busulfan dose. Sperm counts and motility results in different studies had significant heterogeneity. Standard protocols for sperm assessment in animal models were needed to reduce heterogeneity between studies.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work is supported by the Natural Science Foundation of China (No. 81673248).

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Author notes

  1. Ruiyang Pu and Jing Liu are the co-first authors of this article.

Authors and Affiliations

  1. Department of Medical Zoology, School of Basic Medicine, Lanzhou University, Lanzhou, China

    Ruiyang Pu, Wei Zhang, Xiaoyu Ren, Dian Shi & Ning Cheng

  2. The Reproductive Medicine Hospital of the First Hospital of Lanzhou University, Lanzhou, Gansu, China

    Jing Liu, Aiping Zhang, Wei Zhang & Lijun Liu

  3. Key Laboratory of Reproductive Medicine and Embryo of Gansu Province, Lanzhou, China

    Jing Liu, Aiping Zhang, Wei Zhang & Lijun Liu

  4. Institute of Epidemiology and Health Statistics, School of Public Health, Lanzhou University, Lanzhou, China

    Jingli Yang, Xianzhen Long, Honghao Hua, Yanyan Liu, Yuanqin Wu & Yana Bai

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Contributions

Conceptualization: NC, RP; methodology: RP, JL, AZ; software: RP, JL, DS; validation: AZ, XR, YL, WZ; formal analysis: HH, XL, LL, YW; investigation and data curation: RP, WZ; writing-original draft: RP, JY, JL; writing-review and editing: RP, JY, NC; supervision: YB, NC.

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Correspondence to Ning Cheng.

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Pu, R., Liu, J., Zhang, A. et al. Modeling methods for busulfan-induced oligospermia and asthenozoospermia in mice: a systematic review and meta-analysis. J Assist Reprod Genet 40, 19–32 (2023). https://doi.org/10.1007/s10815-022-02674-y

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