Restoration of miR-223-3p expression in aged mouse uteri with Samul-tang administration

During the secretory phase of the estrous cycle, endometrium senescence is accompanied by biological mechanisms such as metabolic dysfunction and epigenetic changes, leading to decreased embryo receptivity and implantation failure. Samul-tang has been reported to improve implantation potential in aged mice.

To uncover the age-related changes in the transcriptomes, we performed QuantSeq 3'mRNA sequencing to compare the mRNA expression patterns in the uteri between young and old mice. Young and old female BALB/c mice were administered distilled water or Samul-tang for 4 weeks, and the corresponding effects on the uteri of aged mice were investigated.

We found 586 differentially expressed genes between the young and old mouse groups. Functional annotation analysis revealed 10 important pathways, including arachidonic acid metabolism and glutathione metabolism, involved in uterine cellular proliferation and decidualization. Using in silico analysis, we identified the three most abundantly interacting microRNAs-miR-223-3p, 155-5p, and 129-5p-with differentially expressed genes associated with important biological pathways. Samul-tang administration restored the expression of miR-223-3p, which could interact with important genes such as histamine ammonia-lyase (Hal) and acid phosphatase 5 (Acp5) for embryo implantation.

Our study demonstrated that uterine aging changes the expression of genes involved in metabolic pathways that are crucial to uterine health, leading to cellular senescence. We postulate that the regulation of miR-223-3p via Samul-tang administration can be of therapeutic importance in cellular senescence.