MicroRNA-122-5p alleviates endometrial fibrosis via inhibiting the TGF-β/SMAD pathway in Asherman's syndrome

  • Reprod Biomed Online. 2023 Nov;47(5):103253. doi: 10.1016/j.rbmo.2023.06.008.
Sijia Chen  1 ,  Yana Ma  1 ,  Xiaoxiao Qiu  2 ,  Mengying Liu  1 ,  Peipei Zhang  3 ,  Cheng Wei  1 ,  Yongdong Dai  1 ,  Linyan Ge  4 ,  Haiyan Zhu  1 ,  Yanling Zhang  1 ,  Jiaren Zhang  4 ,  Xiaona Lin  5
Affiliations
  • 1. Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China.; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No. Qingchun East Road, Jianggan District, Hangzhou, 310016, China.
  • 2. Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China.; Department of Obstetrics and Gynecology, Taizhou Municipal Hospital, Taizhou, 318000, China.
  • 3. Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China.; Department of Obstetrics and Gynecology, Tiantai People's Hospital of Zhejiang Province, Taizhou, 317200, China.
  • 4. Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China.
  • 5. Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China.; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No. Qingchun East Road, Jianggan District, Hangzhou, 310016, China.. Electronic address: [email protected].
PMID: 37677924 DOI: 10.1016/j.rbmo.2023.06.008
Abstract

Research question: What is the effect of miR-122 on the progression and recovery of fibrosis in Asherman's syndrome?

Design: Endometrial tissue was collected from 21 patients, 11 with intrauterine adhesion (IUA) and 10 without IUA. Quantitative real-time polymerase chain reaction, immunofluorescence and Western blot were applied to observe the expression of mRNAs/miRNAs and protein, respectively. The endometrial physical injury was carried out in C57BL/6 mice to create an endometrial fibrosis model, with intrauterine injection of adenovirus to compare the antifibrosis and repair function of miR-122 on endometrium. The morphology of the uterus was observed using haematoxylin and eosin staining, and fibrosis markers were detected by immunohistochemistry.

Results: miR-122 expression was reduced in patients with IUAs, accompanied by fibrosis. MiR-122 overexpression reduced the degree of fibrosis in endometrial stromal cells. Further molecular analyses demonstrated that miR-122 inhibited fibrosis through the TGF-β/SMAD pathway by directly targeting the 3' untranslated region of Smad Family member 3, suppressing its expression. Notably, miR-122 promoted endometrial regeneration and recovery of pregnancy capacity in a mouse endometrial injury model.

Conclusions: miR-122 is a critical regulator for repair of endometrial fibrosis and provided new insight for the clinical treatment of intrauterine adhesions.

Keywords
SMAD transcription factor; fibrosis; intrauterine adhesion; microRNA (miRNA); reproduction; transforming growth factor beta (TGF‐β).
Products