Identification of altered miRNAs and their targets in placenta accreta

Front Endocrinol (Lausanne). 2023 Mar 3:14:1021640. doi: 10.3389/fendo.2023.1021640. eCollection 2023.

Abstract

Placenta accreta spectrum (PAS) is one of the major causes of maternal morbidity and mortality worldwide with increasing incidence. PAS refers to a group of pathological conditions ranging from the abnormal attachment of the placenta to the uterus wall to its perforation and, in extreme cases, invasion into surrounding organs. Among them, placenta accreta is characterized by a direct adhesion of the villi to the myometrium without invasion and remains the most common diagnosis of PAS. Here, we identify the potential regulatory miRNA and target networks contributing to placenta accreta development. Using small RNA-Seq followed by RT-PCR confirmation, altered miRNA expression, including that of members of placenta-specific miRNA clusters (e.g., C19MC and C14MC), was identified in placenta accreta samples compared to normal placental tissues. In situ hybridization (ISH) revealed expression of altered miRNAs mostly in trophoblast but also in endothelial cells and this profile was similar among all evaluated degrees of PAS. Kyoto encyclopedia of genes and genomes (KEGG) analyses showed enriched pathways dysregulated in PAS associated with cell cycle regulation, inflammation, and invasion. mRNAs of genes associated with cell cycle and inflammation were downregulated in PAS. At the protein level, NF-κB was upregulated while PTEN was downregulated in placenta accreta tissue. The identified miRNAs and their targets are associated with signaling pathways relevant to controlling trophoblast function. Therefore, this study provides miRNA:mRNA associations that could be useful for understanding PAS onset and progression.

Keywords: RNA-sequencing; mRNA; miRNA targets; microRNA; placenta; placenta accreta spectrum; pregnancy; trophoblast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endothelial Cells / metabolism
  • Female
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Myometrium
  • Placenta / metabolism
  • Placenta Accreta* / genetics
  • Placenta Accreta* / metabolism
  • Placenta Accreta* / pathology
  • Pregnancy

Substances

  • MicroRNAs

Grants and funding

This work has been supported by the German Research Foundation (DFG, German Research Foundation)- Project number 255955419- Mo2017/2 and Mo2017/3). UM, MM and AG were additionally supported by the German Research Foundation (DFG, grants Ma1550/12-1- Project number 315156279, MA5082/9-1 and GE-2223/2-1 to UM, MM, and AG, respectively), and DM-P by the Interdisciplinary Center for Clinical Research of the Medical Faculty Jena, (IZKF, DMMP FF05). JM-C has received a postgraduate grant from CONACyT (CVU: 446429) and from DAAD (Ref. 91655120). PF-Z received a grant from DAAD (Ref. 91771964). EB received financial support from the Ministry for Economics, Sciences and Digital Society of Thuringia (TMWWDG), under the framework of the Landesprogramm ProDigital (DigLeben-5575/10-9). MM was additionally supported by the Carl-Zeiss-Stiftung (grant FKZ 0563-2.8/738/2). Carl-Zeiss-Stiftung was not involved in the study design, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. We acknowledge support by the German Research Foundation Projekt-Nr. 512648189 and the Open Access Publication Fund of the Thueringer Universitaets- und Landesbibliothek Jena.