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Effects of exposure to PM2.5 during pregnancy on the multigenerational reproductive outcomes of male mouse offspring and the role of Sertoli cells

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Abstract

There is a paucity of studies on the multigenerational reproductive toxicity of fine particle matter (PM2.5) exposure during pregnancy on male offspring and the underlying mechanisms. This study explored the effects of PM2.5 exposure during pregnancy on the spermatogenesis of three consecutive generations of male mouse offspring. We randomized pregnant C57BL/6 mice into the control group, the Quartz Fiber Membrane control group, and two experimental groups exposed to different concentrations of PM2.5 (4.8 and 43.2 mg/kg B.Wt.). Pregnant mice from experimental groups received intratracheal instillation of PM2.5 of different doses on a three-day basis until birth. F1 mature male offspring from PM2.5-exposed pregnant mice were mated with normal female C57BL/6 mice. Likewise, their F2 mature male followed the same to produce the F3 generation. The results showed that PM2.5 exposure during pregnancy led to decreased body and tail length, body weight, and survival rates, decreased sperm concentration and sperm motility, and increased sperm abnormality rates significantly in F1 male offspring. We barely observed significant impacts of PM2.5 on the birth number, survival rates, and index of testes in the F2 and F3 offspring. Further exploration showed that PM2.5 exposure during pregnancy caused the morphological abnormality of Sertoli cells, downregulated androgen receptor (AR) and connexin43, upregulated anti-Müllerian hormone (AMH), cytokeratin-18 (CK-18), caspase-3, and cleaved caspase-3, decreased thyroid-stimulating hormone (TSH) and testosterone (T), and increased triiodothyronine (T3) in F1 male mouse offspring. Overall, we hypothesize that PM2.5 exposure during pregnancy mainly negatively impacts spermatogenesis in the F1 offspring. The possible mechanism could be that PM2.5 exposure during pregnancy disrupts endocrine hormone release in the F1 generation, thereby influencing the maturation and proliferation of their Sertoli cells and hindering spermatogenesis. This study for the first time investigates the role of Sertoli cells in the reproductive toxicity of PM2.5 on offspring.

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Data availability

The datasets analyzed in this study are available from the corresponding author upon reasonable request.

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Funding

The current study obtained support from the Fundamental Research Funds for the Central Universities (BMU2021YJ020), National Natural Science Foundation of China (81803273), and Beijing Key Laboratory of Environmental Toxicology (2021hjd101).

Author information

Authors and Affiliations

  1. School of Nursing, Peking University, Beijing, 100191, China

    Jing Huang, Hong Lu, Qifang Huang & Lihua Ren

  2. Nursing Department, The University of Hong Kong-Shenzhen Hospital, Shenzhen, 518040, China

    Jiwei Du

  3. Department of Histology and Embryology, Binzhou Medical University, Yan Tai, 264003, China

    Lianshuang Zhang

  4. Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100037, China

    Jialiu Wei

  5. School of Public Health, Xi’an Jiaotong University Health Science Centre, Xi’an, China

    Shaowei Wu

  6. School of Public Health, Capital Medical University, Beijing, 10069, China

    Xianqing Zhou

Authors
  1. Jing Huang
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  2. Hong Lu
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  3. Jiwei Du
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  9. Lihua Ren
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Contributions

All authors contributed to the study’s conception and design. Jing Huang performed investigation, conceptualization, writing—original draft preparation. Hong Lu was responsible for data curation, supervision, project administration. Jiwei Du did supervision, project administration. Lianshuang Zhang did investigation and provided resources. Jialiu Wei did investigation. Qifang Huang did data curation. Gantuya Dorj contributed to conceptualization, writing—review and editing. Enkhjargal Gombojav contributed to conceptualization, writing—review and editing. Shaowei Wu provided resources. Xianqing Zhou was responsible for funding acquisition, supervision. Lihua Ren was responsible for funding acquisition, supervision, writing—review and editing. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Lihua Ren.

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Ethical approval

The present animal study obtained approval from the Animal Experiments and Experimental Animal Welfare Committee of PKUHSC (Approval No. LA2018095). All the animal experiments in this study were guided by the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

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Huang, J., Lu, H., Du, J. et al. Effects of exposure to PM2.5 during pregnancy on the multigenerational reproductive outcomes of male mouse offspring and the role of Sertoli cells. Environ Sci Pollut Res 30, 103823–103835 (2023). https://doi.org/10.1007/s11356-023-29751-8

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