The Function of TrophomiRs and Other MicroRNAs in the Human Placenta

Sadovsky, Yoel; Mouillet, Jean-François; Ouyang, Yi‐Bing; Bayer, Avraham; Coyne, Carolyn B.

doi:10.1101/cshperspect.a023036

Cited by 62 publications

(62 citation statements)

References 176 publications

(204 reference statements)

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“…In the present work we did not pursue the exact distribution of C19MC miRNA among extracellular vesicles or in a protein-bound form in the plasma, as demonstrated previously [11,21,31,37–39]. Nonetheless, we confirmed the rising levels of C19MC miRNA in exosomes early in pregnancy.…”

Section: Discussionsupporting

confidence: 67%

“…Members of this cluster are expressed at a very low level in extravillous trophoblast relative to non-invasive villous trophoblast, and over-expression of C19MC miRNA attenuates migration of extravillous trophoblasts [19]. Furthermore, we found that primary human villous trophoblasts are resistant to infection by diverse DNA and RNA viruses, and this effect could be conferred to other, non-placental cell types by transfecting them with C19MC miRNA, or exposing them to exosomes that contained C19MC miRNA [20,21]. This effect is specific to viruses, as C19MC miRNAs have no effect on infection by intracellular bacteria or protozoa [22].…”

Section: Introductionmentioning

confidence: 99%

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The expression level of C19MC miRNAs in early pregnancy and in response to viral infection

et al. 2017

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Introduction We have previously shown that miRNAs produced from the Chromosome 19 MiRNA Cluster (C19MC), which are expressed almost exclusively in primate trophoblasts and are released into the maternal circulation, reduce viral replication in non-placental cells and can modulate migratory behavior of extravillous trophoblast. We sought to define the expression pattern of C19MC miRNA in early pregnancy and in response to viral infection in vitro and in vivo. Methods We prospectively followed women undergoing in vitro fertilization (IVF) and determined their blood level of C19MC miRNA using RT-qPCR. To examine the effect of viral exposure on C19MC miRNAs expression, we used three systems: (1) a transgenic mouse overexpressing the C19MC cluster and exposed to Togaviridae during pregnancy, (2) cultured primary human trophoblasts exposed to Vesicular Stomatitis Virus in vitro, and (3) amniotic fluid from women exposed to cytomegalovirus during pregnancy. Results In 27 IVF pregnancies, C19MC miRNAs were detected as early as 2 weeks after implantation, and their levels increased thereafter. There was no change in C19MC miRNA expression levels in the mouse placenta in response to viral exposure. Similarly, Vesicular Stomatitis Virus infection of primary human trophoblast did not selectively increase C19MC miRNA expression. C19MC miRNA expression in the amniotic fluid was not affected by vertical transmission of cytomegalovirus. Discussion The expression of C19MC miRNAs in maternal circulation very early in pregnancy suggests a role in the establishment of the maternal-fetal interface. The levels of C19MC miRNA are not influenced by diverse types of viral infection.

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Section: Discussionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

The expression level of C19MC miRNAs in early pregnancy and in response to viral infection

et al. 2017

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“…We recently reported that cultured primary human trophoblasts (PHTs) are highly resistant to infection by diverse and unrelated viruses and that conditioned PHT culture medium confers resistance to viral infections in nonplacental recipient cells (18). Of importance, we found that C19MC miRNAs are packaged within PHT‐derived exosomes and are released to the extracellular medium where they confer viral resistance to recipient cells by inducing autophagy (18, 19).…”

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confidence: 99%

Expression and trafficking of placental microRNAs at the feto‐maternal interface

et al. 2017

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During pregnancy, placental trophoblasts at the feto-maternal interface produce a broad repertoire of microRNA (miRNA) species. These species include miRNA from the primate-specific chromosome 19 miRNA cluster (C19MC), which is expressed nearly exclusively in the placenta. Trafficking of these miRNAs among the maternal, placental, and fetal compartments is unknown. To determine miRNA expression and trafficking patterns during pregnancy, we sequenced miRNAs in triads of human placenta and of maternal and fetal blood and found large subject-to-subject variability, with C19MC exhibiting compartment-specific expression. We therefore created humanized mice that transgenically express the entire 160-kb human C19MC locus or lentivirally express C19MC miRNA members selectively in the placenta. C19MC transgenic mice expressed a low level of C19MC miRNAs in diverse organs. When pregnant, female C19MC mice exhibited a strikingly elevated (>40-fold) expression of C19MC miRNA in the placenta, compared with other organs, that resembled C19MC miRNAs patterns in humans. Our mouse models showed that placental miRNA traffic primarily to the maternal circulation and that maternal miRNA can traffic to the placenta and even into the fetal compartment. These findings define an extraordinary means of nonhormonal, miRNA-based communication between the placenta and feto-maternal compartments.-Chang, G., Mouillet, J.-F., Mishima, T., Chu, T., Sadovsky, E., Coyne, C. B., Parks, W. T., Surti, U., Sadovsky, Y. Expression and trafficking of placental microRNAs at the feto-maternal interface.

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“…These biomolecules may affect maternal and fetal tissues, including potential suppression of a maternal immune response against the developing fetus and trophoblast cell migration (24,25). They may also serve as useful biomarkers of pregnancy-related diseases, such as preeclampsia, and fetal trisomy 21 (26 -30).…”

Section: Humanmentioning

confidence: 99%

Sex-Specific Placental Responses in Fetal Development

2015

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The placenta is an ephemeral but critical organ for the survival of all eutherian mammals and marsupials. It is the primary messenger system between the mother and fetus, where communicational signals, nutrients, waste, gases, and extrinsic factors are exchanged. Although the placenta may buffer the fetus from various environmental insults, placental dysfunction might also contribute to detrimental developmental origins of adult health and disease effects. The placenta of one sex over the other might possess greater ability to respond and buffer against environmental insults. Given the potential role of the placenta in effecting the lifetime health of the offspring, it is not surprising that there has been a resurging interest in this organ, including the Human Placental Project launched by the National Institutes of Child Health and Human Development. In this review, we will compare embryological development of the laboratory mouse and human chorioallantoic placentae. Next, evidence that various species, including humans, exhibit normal sex-dependent structural and functional placental differences will be examined followed by how in utero environmental changes (nutritional state, stress, and exposure to environmental chemicals) might interact with fetal sex to affect this organ. Recent data also suggest that paternal state impacts placental function in a sex-dependent manner. The research to date linking placental maladaptive responses and later developmental origins of adult health and disease effects will be explored. Finally, we will focus on how sex chromosomes and epimutations may contribute to sex-dependent differences in placental function, the unanswered questions, and future directions that warrant further consideration.

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The Function of TrophomiRs and Other MicroRNAs in the Human Placenta

Cited by 62 publications

References 176 publications

The expression level of C19MC miRNAs in early pregnancy and in response to viral infection

The expression level of C19MC miRNAs in early pregnancy and in response to viral infection

Expression and trafficking of placental microRNAs at the feto‐maternal interface

Sex-Specific Placental Responses in Fetal Development

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