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Improvement of Astragalin on Spermatogenesis in Oligoasthenozoospermia Mouse Induced by Cyclophosphamide

  • Reproductive Biology: Original Article
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Abstract

More than 40% of infertile men are diagnosed with oligoasthenozoospermia and the incidence is still rising, but the effective treatments are not been found until now. Astragalin, one of the main active ingredients in traditional Chinese medicine, may be effective in the treatment of oligoasthenozoospermia. This study investigated the pharmacological effects of astragalin for treatment of oligoasthenozoospermia in male mice, induced by cyclophosphamide (CTX). Male mice were intraperitoneally injected by CTX (50 mg/kg), and astragalin (30 mg/kg) was given via oral gavage once daily. RNA-seq analysis highlighted astragalin upregulated gene expression of anti-apoptosis (AKT1and BCL2-XL), cell proliferation (ETV1, MAPKAPK2, and RPS6KA5) and synthesis of testosterone (STAR, CYP11A1, and PRKACB), but downregulated gene expression of cell apoptosis (BAD, BCL-2, CASPASE9, and CASPASE3) in mouse testis. Astragalin also significantly reversed the reduction in body weight, reproductive organs index, and sperm parameters (sperm concentration, viability, and motility) induced by CTX, and restored testicular abnormal histopathologic morphology induced by CTX. Furthermore, astragalin dramatically rescued the gene expression related to spermatogenesis (AKT1, BCL-2, CASPASE9, CASPASE3, MAPKAPK2, RPS6KA5, STAR, and PRKACB), and increased the level of testosterone by improving related proteins (STAR, CYP11A1, PRKACB) for oligoasthenozoospermia induced by CTX. In conclusion, astragalin may be a potential beneficial agent for oligoasthenozoospermia by increasing the testosterone levels in testis.

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Data Availability

All the data is contained in the manuscript, raw datasets used and/or analyzed during the current study is available from the corresponding author on reasonable request.

Abbreviations

CTX:

Cyclophosphamide

BAD:

BCL2-associated agonist of cell death

BCL-2:

B cell leukemia/lymphoma 2

CASPASE9:

Cysteinyl aspartate specific proteinase 9

CASPASE3:

Cysteinyl aspartate specific proteinase 3

AKT1:

Thymoma viral proto-oncogene 1

BCL2-XL:

BCL2-associated X protein

ETV1:

ETS variant 1

MAPKAPK2:

MAP kinase-activated protein kinase 2

RPS6KA5/MSK1:

Ribosomal protein S6 kinase, polypeptide 5

STAR:

Steroidogenic acute regulatory protein

PRKACB:

Protein kinase, cAMP dependent regulatory, type II alpha

CYP11A1:

Cytochrome P450, family 11, subfamily a, polypeptide 1

LH:

Luteinizing hormone

DEGs:

Differentially expressed genes

GO:

Gene ontology

BP:

Biological process

MF:

Molecular function

CC:

Cellular component

KEGG:

Kyoto Encyclopedia of Genes and Genomes

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Funding

This study was supported by the National Natural Science Foundation of China (No. 81960278), the Outstanding Youth Funds of Science and Technology Department of Gansu Province (No. 20JR5RA371), the Gansu Provincial Health and Family Planning Commission (GSWSKY2017-34), and the Science Foundation of the Gansu Province, China (20YF3FA030), Fundamental Research Funds for the Central Universities (No. lzujbky-2021-kd38).

Author information

Authors and Affiliations

  1. The First Clinical Medical College of Lanzhou University, Lanzhou, China

    Qigang Fan, Zhongying Zhao, Ruifeng He, Meigui Zhang, Yi Li & Qinying Zhu

  2. School of Life Sciences, Lanzhou University, Lanzhou, China

    Qing Meng

  3. Department of Obstetrics and Gynecology, Key Laboratory for Gynecologic Oncology Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China

    Hongli Li, Lihui Zhao & Xiaolei Liang

  4. Second Clinical Medical College of Lanzhou University, Lanzhou, China

    Pu Gao, Xinlong Li & Fengqin Shen

Authors
  1. Qigang Fan
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  2. Zhongying Zhao
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  9. Yi Li
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  12. Lihui Zhao
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  13. Xiaolei Liang
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Contributions

Xiaolei Liang, Qigang Fan, Qing Meng, and Hongli Li designed the study. Qigang Fan, Pu Gao, and Fengqin Shen performed the animal studies and finished all the experiments. Zhongying Zhao, Ruifeng He, and Meigui Zhang analyzed the data. Yi Li, Qinying Zhu, Hongli Li, and Xinlong Li prepared the draft figures and tables. Xiaolei Liang, Qigang Fan, and Qing Meng prepared the manuscript. All authors have reviewed the final manuscript.

Corresponding author

Correspondence to Xiaolei Liang.

Ethics declarations

Ethics Approval and Consent to Participate

This study makes the use of male C57BL/6 N mice, and all the experimental protocol for the use of animal was approved the Ethics Committee of The First Hospital of Lanzhou University (LDYYLL2019-44).

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Not applicable.

Competing Interests

The authors declare no competing interests.

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Fan, Q., Zhao, Z., Meng, Q. et al. Improvement of Astragalin on Spermatogenesis in Oligoasthenozoospermia Mouse Induced by Cyclophosphamide. Reprod. Sci. 29, 1738–1748 (2022). https://doi.org/10.1007/s43032-021-00808-8

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  • DOI: https://doi.org/10.1007/s43032-021-00808-8

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