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

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

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).

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