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MicroRNAs in placental health and disease
Open accessAbstract
MicroRNAs (miRNAs) constitute a large family of small noncoding RNAs that are encoded by the genomes of most organisms. They regulate gene expression through posttranscriptional mechanisms to attenuate protein output in various genetic networks. The discovery of miRNAs has transformed our understanding of gene regulation and sparked intense efforts intended to harness their potential as diagnostic markers and therapeutic tools. Over the last decade, a flurry of studies has shed light on placental miRNAs but has also raised many questions regarding the scope of their biologic action. Moreover, the recognition that miRNAs of placental origin are released continually in the maternal circulation throughout pregnancy suggested that circulating miRNAs might serve as biomarkers for placental function during pregnancy. Although this generated much enthusiasm, recently recognized challenges have delayed the application of miRNA-based biomarkers and therapeutics in clinical practice. In this review, we summarize key findings in the field and discuss current knowledge related to miRNAs in the context of placental biology.
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“The human placenta expresses a wide variety of non-coding RNAs (398), but few data are available regarding their responsiveness to hypoxia.”
From Placental Origins of Chronic Disease (2016) · cites this paper as [398]
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Guerrero-Muñoz, J., Medina, L., Castillo, C., Liempi, A. I., Fernández-Moya, A., Araneda, S., Ortega, Y., Rojas-Pirela, M., Maya, J. D., & Kemmerling, U. (2023) · Placenta · doi:10.1016/j.placenta.2023.10.009 · Cited by 6
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“Placental miRNA is known to be present, and stable, in maternal plasma(23) and is believed to be released from the syncytiotrophoblast and carried in the plasma in at least two forms: protein‐bound miRNA and vesicular miRNA.(24) They are cleared from the maternal circulation soon after delivery.”
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Krawczynski, K., Ouyang, Y., Mouillet, J., Chu, T., Coyne, C. B., & Sadovsky, Y. (2020) · Journal of Cell Science · doi:10.1242/jcs.246769 · Cited by 5
“Several groups, including our laboratory, have shown that miRNAs expressed from the chromosome 19 miRNA cluster (C19MC) are the most abundantly expressed miRNAs in human placental trophoblasts (Noguer-Dance et al., 2010; Bortolin-Cavaille et al., 2009; Bellemer et al., 2012; Donker et al., 2012; Mouillet et al., 2015;…”
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“They were first described in the nematode Caenorhabditis elegans (Lee et al., 1993; Wightman et al., 1993) and later found in the genomes of protists, plants, animals, and viruses (Mouillet et al., 2015).”
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Pereira, I. D. S., Cortez, M. R., de Arruda, T. S., Carneiro, F. M., da Cruz, A. B., Gava, R., de Faria, G. M., Truzzi, I. G. D. C., Spegiorin, L. C. J. F., Muxel, S. M., et al. (2025) · Parasite Immunology · doi:10.1111/pim.70032 · Cited by 3
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“Role of epigenetics in the fetal brain programming is a widely-investigated research topic because epigenetic regulation is widespread in the placenta as well as fetal brain (Nelissen et al. 2011; Petanjek and Kostović 2012; Mouillet et al. 2015; Martin et al. 2017; Klemm et al. 2019).”
Blood Pressure and Late Pregnancy Circulating miRNAs in the MADRES Study
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“Placental miRNA may be involved in maternal adaptations to pregnancy [15, 16] and fetal growth outcomes.”
BackgroundSelf-citationCytoplasmic and nuclear DROSHA in human villous trophoblasts
Noguchi, S., Ohkura, S., Negishi, Y., Tozawa, S., Takizawa, T., Morita, R., Takahashi, H., Ohkuchi, A., & Takizawa, T. (2024) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2023.104189 · Cited by 3
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“The human placenta expresses numerous types of miRNA species, with a fraction of these miRNAs being specific to trophoblasts.(20,21) Several studies reported the miRNA profile of maternal blood(22) and placental tissues.”
BackgroundEpigenetic modifications in the human placenta
Robinson, W. P., Peñaherrera, M. S., Konwar, C., Yuan, V., & Wilson, S. L. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-91380-5.00031-9 · Cited by 2
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“It is also known that microRNAs (miRNAs) molecules are involved in the physiological regulation of major processes of placentation [40] .”
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“While the exact functions of these clusters is not fully known, their expression has markedly distinguished the placenta from other organs 100 , and has often observed to differ in cancer 101,102 .”
Esemu, L. F., Awanakam, H., Nanfa, D., Besong, M., Tsayem, I. N., Nkenfou, C. N., Bigoga, J. D., Leke, R. G. F., Sobngwi, E., Ndhlovu, L. C., et al. (2022) · PLoS ONE · doi:10.1371/journal.pone.0268820 · Cited by 2
“Nonetheless, findings by [23] showed how placenta inflammation led to an increase in threshold levels of unbound maternal antibodies causing saturation of placenta FcRn receptors available for efficient antibody transfer.”
BackgroundBedeutung der Molekularpathologie in der Geburtshilfe – Plazenta im Fokus
Karge, A., Enzensberger, C., Stickeler, E., Maurer, J., Kuschel, B., Pecks, U., & Graupner, O. (2023) · Die Gynäkologie · doi:10.1007/s00129-023-05054-4 · Cited by 1
“Durch eine Hemmung der mRNA-Translation und durch eine Destabilisierung der Transkription wird die Genexpression abgeschwächt, was zu einer reduzierten Proteinsynthese führt [51, 52].”
BackgroundmiR-155 suppresses angiotensin II type 1 receptor synthesis during placental morphogenesis
Arthurs, A. L., Lumbers, E. R., Schofield, L. G., Lees, C., Chin, P. Y., Care, A. S., Robertson, S. A., Schjenken, J. E., & Pringle, K. G. (2025) · Cell Death Discovery · doi:10.1038/s41420-025-02892-0 · Cited by 1
“Post-transcriptional regulation by microRNAs (miRNAs) plays a role in this process [1]. miRNAs are short, non-coding RNA fragments that largely act by repressing mRNA translation.”
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Decreased cell-free but not exosomal miR-518b in maternal plasma is caused by amniocentesis
Miura, K., 東島, 愛., Hasegawa, Y., Miura, S., Yoshiura, K., & Masuzaki, H. (2018) · Clinical and Experimental Obstetrics & Gynecology · doi:10.12891/ceog4351.2018
A Two-Pronged Approach to Preeclampsia: Understanding Gene Expression and Targeting sFlt1 using RNAi
Ashar-Patel, A. (2017) · The Journal of the American Medical Association (JAMA) Network (American Medical Association) · doi:10.13028/m2rh4n
“Pri-miRNAs exhibiting particularly high placental expression include the chromosome 14 and 19 miR clusters (C14MC and C19MC, respectively), the miR-371-3 cluster and the mir210 host gene (mir210HG)(Mouillet et al., 2015).”
BackgroundMiura, K., 東島, 愛., Hasegawa, Y., Miura, S., Yoshida, A., & Masuzaki, H. (2018) · Clinical and Experimental Obstetrics & Gynecology · doi:10.12891/ceog4355.2018
Epigenetics and environmental programing of lung disease
Jessen, N., & Joss‐Moore, L. A. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819968-8.00008-1
Trophoblast Extracellular Vesicles in Preeclampsia
Vatish, M., Redman, C. W. G., & Davidge, S. T. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-818417-2.00019-1
MicroARN: la biología molecular como herramienta de predicción en preeclampsia
Díaz, E. S., Sánchez, L. M. M., Roldán-Tabares, M. D., & Jaramillo, L. I. J. (2022) · Clínica e Investigación en Ginecología y Obstetricia · doi:10.1016/j.gine.2021.100740
Takizawa, T., Ohkuchi, A., Matsubara, S., Takeshita, T., & Saito, S. (2018) · Comprehensive gynecology and obstetrics · doi:10.1007/978-981-10-5891-2_13
Eivazi, S., Sabz, F. T. K., Amiri, S., Zandieh, Z., Bakhtiyari, M., Rashidi, M., Aflatoonian, R., Mehraein, F., & Amjadi, F. (2022) · Research Square · doi:10.21203/rs.3.rs-1891148/v1
van de Worp, W. R. P. H. (2022) · Research Publications (Maastricht University) · doi:10.26481/dis.20221214ww
Regulation of fetal brain development in short versus long lived mice
Islam, M. (2022) · MOspace Institutional Repository (University of Missouri) · doi:10.32469/10355/94012
microRNAs in pregnancy: Implications for basic research and clinical management
Xu, P., Shao, X., Liu, M., & Wang, Y. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-91380-5.00006-x
Hernandez, Y.-A., Gonzalez, J., García‐Robles, R., & Aristizábal-Pachón, A. F. (2024) · MicroRNA · doi:10.2174/0122115366268128231201054005
“In our study, we have found that microRNA-1225-5p was overexpressed in the placental tissue that we used as our reference tissue according to the report of Mouillet, et al. [16], but we subsequently found that it was not expressed at all in the luminal A and B cell lines.”
MethodMarkova, K. L., Zementova, M. S., Vashukova, E. S., Pereviazkina, M. A., Selkov, S. А., & Соколов, Д. И. (2023) · Medical Immunology (Russia) · doi:10.15789/1563-0625-moe-2617
do Amaral, C. C., Nedel, F., Ferrúa, C. P., Garcia, T. F., Corrêa, G. P., Giorgi, R., Longoni, A., de Assis, A. M., Quevedo, L. D. Á., Ghisleni, G., et al. (2024) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2024.1322820
Erbilen, E. A., Varol, G. F., Süt, N., Türker, N. P., & Sayin, C. (2024) · Gynecology Obstetrics and Reproductive Medicine · doi:10.21613/gorm.2023.1501
Circulation Transcriptome of Maternal Plasma and Its Use in Noninvasive Prenatal Screening
Kumari, O., & Chawla, L. (2024) · Springer eBooks · doi:10.1007/978-981-97-6402-0_13
Environmental Exposures and Developmental Programing of the Lung
Weinheimer, C., & Joss‐Moore, L. A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95488-4.00100-5
Discovery of placental microRNAs associated with maternal insulin sensitivity during pregnancy
Majid, S., Soukar, I., White, F., Allard, C., Aguet, F., Ardlie, K., Florez, J. C., Edlow, A. G., Jacques, P., Karumanchi, S. A., et al. (2025) · Placenta · doi:10.1016/j.placenta.2025.10.021
Additional file 1 of A blood-based miRNA signature for early non-invasive diagnosis of preeclampsia
Bao, S., Zhou, T., Yan, C., Bao, J., Yang, F., Chao, S., Zhou, M., & Xu, Z. (2022) · Figshare · doi:10.6084/m9.figshare.21087300
Gaylord, A., Mujtaba, M. N., Li, M., Osei, M., Agyei, O., Chillrud, S. N., Kaali, S., Jack, D. W., Asante, K.-P., Wu, H., et al. (2025) · Current Zoology · doi:10.1093/eep/dvaf036
“The human placenta has a rich transcriptome that includes small, non-coding RNAs such as microRNAs (miRNAs) [ 27–29 ]. miRNAs regulate gene expression and play a major role in physiological processes such as developmental timing, stem cell differentiation, and immune responses, which are crucial…”
Spadafora, R., Zhang, J., Nirmala, N. R., Li, X., & O’Tierney-Ginn, P. F. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1736033 · Cited by 1
“MicroRNAs (miRNAs) are small non-coding RNAs that bind to mRNA, repressing translation to protein and leading to transcript degradation; they are important regulators of placental development and function (9).”
Placenta-Specific miRNA miR-515-3p Suppresses HMGB3 Expression in the Breast Cancer Cell Line MCF-7
Sato, A., Takei, H., Noguchi, S., & Takizawa, T. (2026) · Journal of Nippon Medical School · doi:10.1272/jnms.jnms.2026_93-206
Diestra, A., Pando-Caciano, A., Apaza-Quiroz, C. A., Adaui, V., Pinedo-Cancino, V., Sanchez, S. S., Mugnier, M. R., Gilman, R. H., Bowman, N. M., & Pajuelo, M. J. (2026) · Research Square · doi:10.21203/rs.3.rs-10217677/v1
“This pattern is consistent with the notion of placental homeostatic resilience (31).”
Expression Levels of miR-99a and miR-143 in Women Diagnosed with Recurrent Pregnancy Loss
Kouvoutsaki, K., Nazou, E., Mavrogianni, D., Liokari, E., Anagnostaki, I., Tzeli, M., Arkoulis, I., Stavros, S., Rodolakis, A., Drakakis, P., et al. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15155955
“Dysregulation of miRNAs during early fetal development affects cell differentiation and the implantation process [7].”
Hoffmann, I., Maurer, J., Enzensberger, C., Stickeler, E., & Graupner, O. (2026) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-026-08583-0
“They regulate gene expression by directing a splicing complex to a target RNA, resulting in an altered translation process and therefore decreased protein biosynthesis [10, 11].”
Metadata
- Authors
- Mouillet, J.-F., Ouyang, Y., Coyne, C. B., & Sadovsky, Y.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Sadovsky, Yoel
- Venue
- American Journal of Obstetrics and Gynecology
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 213
- Issue
- 4
- Pages
- S163-S172
- ISSN
- 0002-9378 (ISSN-L)
- PMC
- PMC4592520
- OpenAlex
- W2128949071
- Cited by
- 195
- References
- 157
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 13 · 2023: 20 · 2022: 25 · 2021: 25 · 2020: 23 · 2019: 18 · 2018: 19 · 2017: 19 · 2016: 15
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Obstetrics and Gynecology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Pennsylvania Department of Health
- National Institutes of Health (0863906)
- National Institute of Allergy and Infectious Diseases (R01AI081759)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R21HD071707, R01HD065893, R01HD075665)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- microRNA, placenta, placental function, placental disease, circulating microRNAs, pregnancy, biomarkers, post-transcriptional regulation, non-coding RNA, miRNA-based therapy
- MeSH terms
- Extracellular Space, Female, Humans, Placenta Diseases, Pregnancy, Biomarkers, MicroRNAs
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