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Overexpression of miR-200b-3p in Menstrual Blood-Derived Mesenchymal Stem Cells from Endometriosis Women

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Abstract

The key relationship between Sampson’s theory and the presence of mesenchymal stem cells in the menstrual flow (MenSCs), as well as the changes in post-transcriptional regulatory processes as actors in the etiopathogenesis of endometriosis, are poorly understood. No study to date has investigated the imbalance of miRNAs in MenSCs related to the disease. Thus, through literature and in silico analyses, we selected four predicted miRNAs as regulators of EGR1, SNAI1, NR4A1, NR4A2, ID1, LAMC3, and FOSB involved in pathways of apoptosis, angiogenesis, response to steroid hormones, migration, differentiation, and cell proliferation. These genes are frequently overexpressed in the endometriosis condition in our group studies. They were the trigger for the miRNAs search. Therefore, a case–control study was conducted with MenSCs of women with and without endometriosis (ten samples per group). Crossing information obtained from the STRING, PubMed, miRPathDB, miRWalk, and DIANA TOOLS databases, we chose to explore the expression of miR-21-5p, miR-100-5p, miR-143-3p, and miR-200b-3p by RT-qPCR. We found an upregulation of the miR-200b-3p in endometriosis MenSCs (P = 0.0207), with a 7.93-fold change (ratio of geometric means) compared to control. Overexpression of miR-200b has been associated with increased cell proliferation, stemness, and accentuated mesenchymal-epithelial transition process in eutopic endometrium of endometriosis. We believe that dysregulated miR-200b-3p may establish primary changes in the MenSCs, thus favoring tissue implantation at the ectopic site.

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Data Availability

RT-qPCR raw data are available upon request from the corresponding author.

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Acknowledgements

The authors thank Océlia de Vasconcelos for her support in collecting the samples. In addition, we are especially grateful to the women who voluntarily agreed to participate in this work.

Funding

This study was financially supported by the Sao Paulo Research Foundation (FAPESP 2013/22431–3), National Institute of Hormones and Women’s Health (Hormona)-CNPq (INCT-CNPq 465482/2014–7), and CAPES Higher Education Improvement Coordination (Scholarship).

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Authors and Affiliations

  1. Division of Human Reproduction, Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, 3900 Bandeirantes Avenue, Ribeirão Preto, São Paulo, 14049-900, Brazil

    Rafael Zucco de Oliveira, Fabiana de Oliveira Buono, Ana Clara Lagazzi Cressoni, Letícia Bruna Corrêa Penariol, Cristiana Carolina Padovan, Patricia Aparecida Tozetti, Omero Benedito Poli-Neto, Rui Alberto Ferriani, Júlio Cesar Rosa-e-Silva & Juliana Meola

  2. Laboratory for Translational Data Science, Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, 14049-900, Brazil

    Omero Benedito Poli-Neto, Júlio Cesar Rosa-e-Silva & Juliana Meola

  3. National Institute of Hormones and Women’s Health (Hormona), CNPq, Porto Alegre, Rio Grande Do Sul, 90035-003, Brazil

    Rui Alberto Ferriani & Juliana Meola

  4. Center for Cell Therapy and Reginal Blood Center, University of São Paulo, Ribeirão Preto, São Paulo, 14051-140, Brazil

    Maristela Delgado Orellana

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  1. Rafael Zucco de Oliveira
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  2. Fabiana de Oliveira Buono
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  3. Ana Clara Lagazzi Cressoni
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  4. Letícia Bruna Corrêa Penariol
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  5. Cristiana Carolina Padovan
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  6. Patricia Aparecida Tozetti
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  7. Omero Benedito Poli-Neto
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  10. Júlio Cesar Rosa-e-Silva
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  11. Juliana Meola
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Contributions

RZO applied the experiments, analyzed and interpreted the data, and drafted the article. FOB, ACLC, and LBCP performed a literature review, in silico analysis, and interpreted the data. The CCP assisted in the RT-qPCR experiments and the preparation of the laboratory experiments. PAT and MDO helped in cell culture, immunophenotyping, and cell differentiation. OBPN, JCRS, and RAF helped design the study, select the samples, and review the manuscript. JM designed and coordinated the study, supervised the experiments, and edited the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Juliana Meola.

Ethics declarations

Ethics Approval

The Research Ethics Committee of the University Hospital of the Ribeirao Preto Medical School approved this case–control study (HCRP 3644/2019). The MenSC used in this work were collected from November 2014 to December 2016 following the ethics guidelines established by the Declaration of Helsinki (HCRP 15227/2012). They have been transferred to a biorepository of the Human Reproduction Section at the Department of Gynecology and Obstetrics of the Ribeirao Preto Medical School (HCRP 3644/2019).

Consent to Participate

All participants have provided written informed consent (HCRP. 3644/2019, approval date 06/04/2019).

Consent for Publication

All authors have read and approved the manuscript publication.

Conflict of Interest

The authors declare no competing interests.

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de Oliveira, R.Z., de Oliveira Buono, F., Cressoni, A.C.L. et al. Overexpression of miR-200b-3p in Menstrual Blood-Derived Mesenchymal Stem Cells from Endometriosis Women. Reprod. Sci. 29, 734–742 (2022). https://doi.org/10.1007/s43032-022-00860-y

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