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

Abstract

Background 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. Methods 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. Results 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. Conclusion 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.

Systems pharmacology approaches in herbal medicine research: a brief review

“…SWT administration also restored miR-223-3p, which could interact with embryo implantation-related genes (Hal, Acp5) in the uterus of aged mice (97). This transcriptome analysis result was consistent with the phenotypic findings of the protective effect of SWT on the increase of ovarian reserve, ovulated mature oocytes, and pregnancy rate in aged mice (96,97). Tao-Hong-Si-Wu Decoction (THSWD), a traditional herbal medicine, is composed of six herbs (Prunus persica, Carthamus tinctorius, Rehmannia glutinosa, Angelica sinensis, Paeonia lactiflora, and Ligustium chuanxiong).…”

“…SWT administration also restored miR-223-3p, which could interact with embryo implantation-related genes ( Hal , Acp5 ) in the uterus of aged mice ( 97 ). This transcriptome analysis result was consistent with the phenotypic findings of the protective effect of SWT on the increase of ovarian reserve, ovulated mature oocytes, and pregnancy rate in aged mice ( 96 , 97 ).…”

“…Si-Wu-Tang (SWT) (Samul-tang in Korean, Shimotsu-to in Japanese) is one of the most popular herbal prescriptions consisting of four herbs including Paeonia Radix, Ligusticum Rhizoma, Rehmannia Radix, and Angelica Radix at a 1:1:1:1 ratio. It has been clinically applied for centuries in Asia to treat symptoms of hematological disorders such as anemia, menstrual irregularities, dysmenorrhea, and menopausal syndrome (89)(90)(91)(92)(93)(94)(95)(96)(97). In recent years, an increasing number of studies have elucidated the MOA of SWT by analyzing SWT-induced changes in gene expression.…”

“…Three microRNAs (miR-200b-3p, miR-665-3p, and miR-667-3p) had binding sites on either Bmp15 or Oas1 mRNA and their expression levels were restored in SWT plus CP-treated mice. Kim and You have http://bmbreports.org BMB Reports also investigated the influence of SWT on ovarian reserve and fertilization in aged mice (＞ 40-week-old) (96,97). They performed functional enrichment analysis of transcriptome data obtained from ovulated ovaries and revealed that RAS signaling pathway-related genes were restored to normal levels as those in young mice after SWT administration to aged mice (96).…”

“…They performed functional enrichment analysis of transcriptome data obtained from ovulated ovaries and revealed that RAS signaling pathway-related genes were restored to normal levels as those in young mice after SWT administration to aged mice (96). SWT administration also restored miR-223-3p, which could interact with embryo implantation-related genes (Hal, Acp5) in the uterus of aged mice (97). This transcriptome analysis result was consistent with the phenotypic findings of the protective effect of SWT on the increase of ovarian reserve, ovulated mature oocytes, and pregnancy rate in aged mice (96,97).…”