2. Academic Validation
  3. Thymopentin alleviates premature ovarian failure in mice by activating YY2/Lin28A and inhibiting the expression of let-7 family microRNAs

Thymopentin alleviates premature ovarian failure in mice by activating YY2/Lin28A and inhibiting the expression of let-7 family microRNAs

  • Cell Prolif. 2021 Aug;54(8):e13089. doi: 10.1111/cpr.13089.
Te Liu 1,  Fangyuan Jing 1,  Peirong Huang 2 3,  Zixiang Geng 4,  Jianghong Xu 5,  Jiahui Li 5,  Danping Chen 5,  Ying Zhu 5,  Zhenxin Wang 6,  Willian Huang 7,  Chuan Chen 1
Affiliations

Affiliations

  • 1 Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • 2 Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3 Center for Advanced Vision Science, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • 4 Department of Acupuncture, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 5 Department of gynaecology, Jingan Hospital of Traditional Chinese Medicine, Shanghai, China.
  • 6 Department of Laboratory Medicine of Zhongshan Hospital and institute of Biomedical Science, Fudan University, Shanghai, China.
  • 7 Hainan Zhonghe Pharmaceutical Co., Ltd, Haikou, China.
PMID: 34180104 DOI: 10.1111/cpr.13089
Abstract

Objective: Thymopentin (5TP) significantly improved typical murine premature ovarian failure (POF) symptoms induced by a high-fat and high-sugar (HFHS) diet. However, its effect and mechanism remain unclear.

Materials and methods: RNA-Seq was used to detect the differentially expressed genes among each group. HFHS-induced POF mouse model was generated and injected with siRNA using Poly (lactic-co-glycolic acid) (PLGA) as a carrier.

Results: RNA-Seq suggested that 5TP promoted the expression of Yin Yang 2 (YY2) in mouse ovarian granulosa cell (mOGC) of HFHS-POF mice. Luciferase reporter assay indicated that 5TP promoted the binding of YY2 to the specific sequence C(C/T)AT(G/C)(G/T) on the Lin28A promoter and promoted Lin28A transcription and expression. We continuously injected PLGA-cross-linked siRNA nanoparticles targeting YY2 into HFHS-POF mice (siYY2@PLGA), which significantly reduced the therapeutic effect of 5TP. siYY2@PLGA injection also significantly attenuated the upregulation of Lin28a expression in mOGCs induced by 5TP and enhanced the expression of let-7 family MicroRNAs, thereby inhibiting the proliferation and division of mOGCs. qPCR results showed that there was a significant difference in the expression levels of exosome-derived Yy2 mRNAs between POF patients and normal women, and that there was a specific correlation between the expression level of exosome-derived Yy2 and the peripheral concentrations of the blood Hormones pregnenolone, progesterone and oestradiol.

Conclusions: Thymopentin promotes the transcriptional activation of Lin28A via stimulating transcription factor YY2 expression, inhibits the activity of let-7 family MicroRNAs and alleviates the ageing of ovarian granulosa cells, ultimately achieving a therapeutic effect on POF in mice.

Keywords

Yin Yang 2 (YY2); exosome; high-fat and high-sugar (HFHS); poly(lactic-co-glycolic acid [PLGA]) nanoparticle; premature ovarian failure.

Figures
Products