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Bisphenol A exposure decreases sperm production and male fertility through inhibition PCBP2 expression

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Abstract

Growing evidence suggests that the exposure of bisphenol A (BPA), an endocrine disruptor that commonly present in the environment, can impair reproduction. However, conflicting results have been reported, and the underlying mechanism has not been fully understood. In this study, 3-week-old male mice were oral exposed to 50 mg/kg/d BPA or equivalent corn oil for 28 days. Their testis and epididymis were then collected for morphology examination by HE stains. The number of sperm was counted, and the morphology was analyzed by PNA (peptide nucleic acid) and pap staining. Fertilization capacity and successful rate were analyzed after mating with wide-type females. Spermatid DNA damage and apoptosis were evaluated by DFI, γH2AX stain, and TUNEL assay. RNA sequencing analysis was conducted to identify differentially expressed genes in testicular tissue of mice exposed to BPA. RNA interference was used to verify the regulatory mechanism of BPA exposure on gene expression in GC-2 cells. Our data showed that the total number of sperm was decreased and the morphology was impaired in BPA-exposed mice. In addition, the serum testosterone level and fertilization efficiency were also reduced. Mechanism studies showed that BPA could suppress the expression of PCBP2, a key regulatory gene in spermatid development, by activating the EZH2/H3K27me3. In conclusion, we found that BPA exposure can impair spermatid development via affecting key gene expression that is at least partially due to epigenetic modification.

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Data openly available in a public repository.

Abbreviations

BPA:

Bisphenol A

LOAEL:

Lowest observed adverse effect level

TUNEL:

Terminal deoxynucleotidyl transferase-mediated nick end labeling

DSB:

DNA double-stranded break

PCBP2:

Poly (rC) binding protein 2

EZH2:

Enhancer of zeste homolog 2

H3K27me3:

Tri-methylate histone H3 (Lys27)

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Acknowledgements

The author thanks all members who helped with the research. We thank Dr. Hengliu for its linguistic assistance during the preparation of this manuscript. The authors thank the editors and reviewers for their significant contributions during the revision period. This project was supported by grants from the National Natural Science Foundation of China (Grant No. 82301804), the China postdoctoral science foundation (Grant No. 2023M734014).

Funding

This project was supported by grants from the National Natural Science Foundation of China (Grant No. 82301804), the China postdoctoral science foundation (Grant No. 2023M734014).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Perinatal Medical Center, The Fifth Affiliated Hospital of Sun Yat-Sen University, No. 52 Meihua East Road, Zhuhai, Guangdong, People’s Republic of China

    Yuming Cao, Jinfeng Xu, Jie Liu, Yan Liang, Fei Ao, Shengnan Wang, Zexiao Wei & Li Wang

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  1. Yuming Cao
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  2. Jinfeng Xu
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  3. Jie Liu
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  4. Yan Liang
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  7. Zexiao Wei
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  8. Li Wang
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Contributions

YC and SW performed the experiments, wrote the manuscript, and made the revisions; JX, JL, YL, and FA analyzed the data. JX and ZW performed RNA extraction sequencing data analysis. LW designed the research and reviewed the manuscript.

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Correspondence to Li Wang.

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Ethics approval

The study was approved by the Ethics Committee of The Fifth Affiliated Hospital of Sun Yat-sen University (No. a2022016).

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We declare that the submitted manuscript does not contain previously published material and is not under consideration for publication elsewhere. Each author has made an important scientific contribution to the study and is thoroughly familiar with the primary data. All authors listed have read the complete manuscript and have approved submission of the paper.

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The authors declare no competing interests.

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11356_2023_30815_MOESM1_ESM.pdf

Figure S1 BPA concentration in testicular tissue of control group and BPA exposure group. (A)-(B) BPA concentration in testicular tissue. N=3, *P < 0.05 by Student’s t-test. (PDF 162 KB)

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Cao, Y., Xu, J., Liu, J. et al. Bisphenol A exposure decreases sperm production and male fertility through inhibition PCBP2 expression. Environ Sci Pollut Res 30, 123309–123323 (2023). https://doi.org/10.1007/s11356-023-30815-y

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