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

Pharm Biol. 2023 Dec;61(1):488-498. doi: 10.1080/13880209.2023.2168705.

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); PI3K/Akt pathway; RNA-seq; SPARC; data-independent acquisition (DIA); sperm chromatin structure assay (SCSA); traditional Chinese medicine (TCM).

MeSH terms

  • Animals
  • DNA Fragmentation
  • Male
  • Mice
  • Mice, Inbred ICR
  • Microplastics* / metabolism
  • Microplastics* / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Plastics* / metabolism
  • Plastics* / pharmacology
  • Polystyrenes / metabolism
  • Polystyrenes / toxicity
  • Proteomics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Semen
  • Spermatozoa

Substances

  • yishen
  • Microplastics
  • tongluo
  • Plastics
  • Polystyrenes
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt

Grants and 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].