Repair mechanism of Yishen Tongluo formula on mouse sperm DNA fragmentation caused by polystyrene microplastics

Abstract

Context

Plastics can break down into millions of microplastic (MPs, < 5 mm) particles in the soil and ocean. These MPs can then affect the function of the reproductive system. There is currently no effective solution to this problem aside from traditional Chinese medicine. We have previously used Yishen Tongluo formula (YSTL) to treat sperm DNA damage caused by some toxic substances.

Objective

To investigate the mechanism underlying the repair of mouse sperm DNA fragmentation caused by polystyrene microplastics by YSTL.

Materials and methods

An animal model of polystyrene microplastic (PS-MP)-induced sperm DNA damage was replicated by gavage of SPF ICR (CD1) mice PS-MPs at 1 mg/d and treated with YSTL at 11.89, 23.78 and 47.56 g/kg, respectively, for 60 days. The Sperm DNA fragmentation index (DFI) of each group was detected and compared. The target genes of YSTL identified by transcriptomic and proteomic analyses were validated by qRT-PCR and western blotting.

Results

The DFI of the PS group (20.66%) was significantly higher than that of the control group (4.23%). The medium and high doses of the YSTL group (12.8% and 11.31%) exhibited a significant repairing effect. The most enriched pathway was PI3K/Akt. TBL1X, SPARC, hnRNP0, Map7D1, Eps8 and Mrpl27 were screened and SPARC was validated.

Discussion and conclusions

The precise mechanism by which YSTL inhibits PD-MPs DNA damage may be associated with the PI3K/Akt pathway and SPARC. It provides a new direction for using traditional Chinese medicine to prevent and repair reproductive system injury caused by MPs.

Keywords:

• Endocrine-disrupting chemical (EDC)
• traditional Chinese medicine (TCM)
• sperm chromatin structure assay (SCSA)
• RNA-seq
• data-independent acquisition (DIA)
• PI3K/Akt pathway
• SPARC

Author contributions

Chenming Zhang and Zulong Wang: Methodology, project administration and writing-original draft. Sicheng Ma: Resources. Rubing Chen: Formal analysis. Shiqi Wang: Data curation. Hao Zhang: Validation. Zhong Hua: Visualization. Zulong Wang & Zixue Sun: Study conceptualization, funding acquisition, writing- reviewing & editing. All writers have reviewed and approved the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [82174377], the China Postdoctoral Science Foundation Project [2022M721068], the Science and Technology Program of Henan Province [192102310159], the Key scientific research Project of colleges and universities in Henan Province [23A360005], the Special Scientific Research Project of National TCM Clinical Research Base [2021JDZX2056] and Innovative Training program for College students in Henan Province [202210471022 and 202210471057].