2. Academic Validation
  3. MiR-135a-5p regulates window of implantation by suppressing pinopodes development and decidualization of endometrial stromal cells

MiR-135a-5p regulates window of implantation by suppressing pinopodes development and decidualization of endometrial stromal cells

  • J Assist Reprod Genet. 2024 Mar 21. doi: 10.1007/s10815-024-03088-8.
Yunan He 1 2,  Ying Ju 1 2,  Hui Lei 1 2,  Jie Dong 1 2,  Ni Jin 1 2,  Jie Lu 1 2,  Shuqiang Chen 3 4,  Xiaohong Wang 5 6
Affiliations

Affiliations

  • 1 Reproductive Medicine Center, Department of Gynecology and Obstetrics, Tangdu Hospital, Air Force Medical University, No.1 Xinsi Road, Baqiao District, Xi'an, Shaanxi, China.
  • 2 Clinical Research Center for Reproductive Medicine and Gynecological Endocrine Diseases of Shaanxi Province, Xi'an, Shaanxi, China.
  • 3 Reproductive Medicine Center, Department of Gynecology and Obstetrics, Tangdu Hospital, Air Force Medical University, No.1 Xinsi Road, Baqiao District, Xi'an, Shaanxi, China. [email protected].
  • 4 Clinical Research Center for Reproductive Medicine and Gynecological Endocrine Diseases of Shaanxi Province, Xi'an, Shaanxi, China. [email protected].
  • 5 Reproductive Medicine Center, Department of Gynecology and Obstetrics, Tangdu Hospital, Air Force Medical University, No.1 Xinsi Road, Baqiao District, Xi'an, Shaanxi, China. [email protected].
  • 6 Clinical Research Center for Reproductive Medicine and Gynecological Endocrine Diseases of Shaanxi Province, Xi'an, Shaanxi, China. [email protected].
PMID: 38512656 DOI: 10.1007/s10815-024-03088-8
Abstract

Purpose: The window of implantation (WOI) is a brief period during which the endometrium is receptive to embryo implantation. This study investigated the relationship between miR-135a-5p and endometrial receptivity.

Methods: Peripheral blood was collected on the day of ovulation and the 5th day after ovulation for high-throughput sequencing from women who achieved clinical pregnancy through natural cycle frozen embryo transfer. RT-qPCR assessed miR-135a-5p expression in the endometrium tissue or cells during the mouse implantation window or decidualization. Scanning electron microscopy was utilized to observe pinopode morphology and quantity in mice overexpressing miR-135a-5p during the WOI. Human endometrial stromal cells (HESC) and artificial induction of mouse uterine decidualization were used to explore whether miR-135a-5p overexpression inhibits decidualization by regulating HOXA10 and BMPR2. Furthermore, the impact of miR-135a-5p on HESC proliferation and HTR8/SVneo invasion was explored.

Results: A total of 54 women were enrolled in the study. bioinformatics analysis and animal models demonstrated that miR-135a-5p was significantly downregulated during the WOI, and its high expression can lead to abnormal pregnancy outcomes. Overexpression of miR-135a-5p resulted in the absence of pinopode in mouse endometrial tissue during the WOI. High miR-135a-5p levels were found to potentially inhibit endometrial tissue decidualization by downregulating HOXA10 and BMPR2 expression. Finally, CEBPD was identified as a potential regulator of miR-135a-5p, which would explain the decreased miR-135a-5p expression during the WOI.

Conclusion: MiR-135a-5p expression is significantly downregulated during the WOI. High miR-135a-5p levels suppress pinopode development and endometrial tissue decidualization through HOXA10 and BMPR2, contributing to inadequate endometrial receptivity.

Keywords

BMPR2; CEBPD; Endometrial receptivity; Endometrial stromal cell; HOXA10; Window of implantation; microRNA.

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