The Function of TrophomiRs and Other MicroRNAs in the Human Placenta

Overview

Journal Cold Spring Harb Perspect Med

Specialty General Medicine

Date 2015 Apr 17

PMID 25877393

Citations 42

Authors

Yoel Sadovsky

Jean-Francois Mouillet

Yingshi Ouyang

Avraham Bayer

Carolyn B Coyne

Affiliations

Soon will be listed here.

Abstract

In eutherian organisms, the placenta interfaces the fetal and maternal environments. Located at the placental villous surface, in direct contact with maternal blood, is the trophoblast layer, which mediates the crucial maternal-fetal exchange of gases, nutrients, and waste products, produces hormones that support the pregnancy, and provides immunologic defense. Discovery of microRNAs (miRNAs) and their role in development, differentiation, and homeostatic resilience has increased our understanding of genomic and epigenomic networks that regulate placental function. Moreover, unique miRNA species, which are expressed by human trophoblasts and are termed "trophomiRs," may show specialized functions during normal and pathological pregnancies. Placental miRNAs, packaged within exosomes and other vesicles or bound in protein complexes, are capable of communicating distinctive signals to maternal and/or fetal tissues. Additional research may usher in the use of circulating miRNAs as pregnancy-related disease biomarkers, providing new diagnostic and therapeutic options during pregnancy.

Citing Articles

Understanding Host-Pathogen Interactions in Congenital Chagas Disease Through Transcriptomic Approaches.

Caceres T, Patino L, Ramirez J Pathogens. 2025; 14(2).

PMID: 40005483 PMC: 11858232. DOI: 10.3390/pathogens14020106.

Profiling the cell-specific small non-coding RNA transcriptome of the human placenta.

Telkar N, Hui D, Penaherrera M, Yuan V, Martinez V, Stewart G Res Sq. 2025; .

PMID: 39989957 PMC: 11844636. DOI: 10.21203/rs.3.rs-5953518/v1.

The expression of chromosome 19 miRNA cluster members during insulin sensitivity changes in pregnancy.

Alvarado-Flores F, Chu T, Catalano P, Sadovsky Y, OTierney-Ginn P Placenta. 2025; 161:23-30.

PMID: 39847922 PMC: 11867847. DOI: 10.1016/j.placenta.2025.01.007.

Prenatal maternal stress in rats alters the epigenetic and transcriptomic landscape of the maternal-fetal interface across four generations.

King S, Schatz N, Babenko O, Ilnytskyy Y, Kovalchuk I, Metz G Commun Biol. 2025; 8(1):38.

PMID: 39794497 PMC: 11723964. DOI: 10.1038/s42003-024-07444-3.

Extracellular Vesicles as Biomarkers of Pregnancy Complications.

Popova A, Vashukova E, Illarionov R, Maltseva A, Pachuliia O, Postnikova T Int J Mol Sci. 2024; 25(22).

PMID: 39596014 PMC: 11594130. DOI: 10.3390/ijms252211944.

References

Zhu X, Han T, Sargent I, Yin G, Yao Y . Differential expression profile of microRNAs in human placentas from preeclamptic pregnancies vs normal pregnancies. Am J Obstet Gynecol. 2009; 200(6):661.e1-7. DOI: 10.1016/j.ajog.2008.12.045. View

Flor I, Bullerdiek J . The dark side of a success story: microRNAs of the C19MC cluster in human tumours. J Pathol. 2012; 227(3):270-4. DOI: 10.1002/path.4014. View

Moya P, Wendland J, Salemme J, Fried R, Murphy D . miR-15a and miR-16 regulate serotonin transporter expression in human placental and rat brain raphe cells. Int J Neuropsychopharmacol. 2012; 16(3):621-9. DOI: 10.1017/S1461145712000454. View

Mouillet J, Donker R, Mishima T, Cronqvist T, Chu T, Sadovsky Y . The unique expression and function of miR-424 in human placental trophoblasts. Biol Reprod. 2013; 89(2):25. PMC: 4076361. DOI: 10.1095/biolreprod.113.110049. View

Tsutsumi A, Kawamata T, Izumi N, Seitz H, Tomari Y . Recognition of the pre-miRNA structure by Drosophila Dicer-1. Nat Struct Mol Biol. 2011; 18(10):1153-8. DOI: 10.1038/nsmb.2125. View

Vickers K, Palmisano B, Shoucri B, Shamburek R, Remaley A . MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol. 2011; 13(4):423-33. PMC: 3074610. DOI: 10.1038/ncb2210. View

Krol J, Loedige I, Filipowicz W . The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010; 11(9):597-610. DOI: 10.1038/nrg2843. View

Lehnert S, Van Loo P, Thilakarathne P, Marynen P, Verbeke G, Schuit F . Evidence for co-evolution between human microRNAs and Alu-repeats. PLoS One. 2009; 4(2):e4456. PMC: 2637760. DOI: 10.1371/journal.pone.0004456. View

Guo L, Tsai S, Hardison N, James A, Motsinger-Reif A, Thames B . Differentially expressed microRNAs and affected biological pathways revealed by modulated modularity clustering (MMC) analysis of human preeclamptic and IUGR placentas. Placenta. 2013; 34(7):599-605. PMC: 3677766. DOI: 10.1016/j.placenta.2013.04.007. View

10.

Mouillet J, Ouyang Y, Bayer A, Coyne C, Sadovsky Y . The role of trophoblastic microRNAs in placental viral infection. Int J Dev Biol. 2014; 58(2-4):281-9. PMC: 4377297. DOI: 10.1387/ijdb.130349ys. View

11.

Guo H, Ingolia N, Weissman J, Bartel D . Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010; 466(7308):835-40. PMC: 2990499. DOI: 10.1038/nature09267. View

12.

Lee D, Romero R, Kim J, Tarca A, Montenegro D, Pineles B . miR-210 targets iron-sulfur cluster scaffold homologue in human trophoblast cell lines: siderosis of interstitial trophoblasts as a novel pathology of preterm preeclampsia and small-for-gestational-age pregnancies. Am J Pathol. 2011; 179(2):590-602. PMC: 3160082. DOI: 10.1016/j.ajpath.2011.04.035. View

13.

Fu G, Ye G, Nadeem L, Ji L, Manchanda T, Wang Y . MicroRNA-376c impairs transforming growth factor-β and nodal signaling to promote trophoblast cell proliferation and invasion. Hypertension. 2013; 61(4):864-72. DOI: 10.1161/HYPERTENSIONAHA.111.203489. View

14.

Tay Y, Rinn J, Pandolfi P . The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014; 505(7483):344-52. PMC: 4113481. DOI: 10.1038/nature12986. View

15.

Gu Y, Sun J, Groome L, Wang Y . Differential miRNA expression profiles between the first and third trimester human placentas. Am J Physiol Endocrinol Metab. 2013; 304(8):E836-43. PMC: 3625781. DOI: 10.1152/ajpendo.00660.2012. View

16.

Fukunaga R, Han B, Hung J, Xu J, Weng Z, Zamore P . Dicer partner proteins tune the length of mature miRNAs in flies and mammals. Cell. 2012; 151(3):533-46. PMC: 3609031. DOI: 10.1016/j.cell.2012.09.027. View

17.

Morales-Prieto D, Chaiwangyen W, Ospina-Prieto S, Schneider U, Herrmann J, Gruhn B . MicroRNA expression profiles of trophoblastic cells. Placenta. 2012; 33(9):725-34. DOI: 10.1016/j.placenta.2012.05.009. View

18.

Hutvagner G, McLachlan J, Pasquinelli A, Balint E, Tuschl T, Zamore P . A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science. 2001; 293(5531):834-8. DOI: 10.1126/science.1062961. View

19.

Maccani M, Marsit C . Exposure and fetal growth-associated miRNA alterations in the human placenta. Clin Epigenetics. 2012; 2(2):401-4. PMC: 3365392. DOI: 10.1007/s13148-011-0046-2. View

20.

Buckberry S, Bianco-Miotto T, Roberts C . Imprinted and X-linked non-coding RNAs as potential regulators of human placental function. Epigenetics. 2013; 9(1):81-9. PMC: 3928189. DOI: 10.4161/epi.26197. View