Placental microRNAs: Responders to environmental chemicals and mediators of pathophysiology of the human placenta

Addo, Kezia A; Palakodety, Niharika; Hartwell, Hadley J.; Tingare, Aishani; Fry, Rebecca C.

doi:10.1016/j.toxrep.2020.08.002

Cited by 33 publications

(20 citation statements)

References 157 publications

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“…Over the past decade, considerable researches have been conducted on ncRNAs in pregnancy-related diseases, of which miRNAs play a central role. Dysregulation of miRNAs from the placenta was proved to influence placental progression and function and these miRNAs to export to the mother and fetus, thus directly affecting maternal and fetal physiology (77)(78)(79). Our data showed that many miRNAs (e.g., miR-191, miR-224, miR-374a, miR-193b, miR-365a, miR-4287, miR-590, miR-664b, miR-3622b, etc.)…”

Section: Discussionmentioning

confidence: 71%

Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction

Yang

Huang

et al. 2021

Front. Immunol.

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Many studies have confirmed that extrachromosomal circular DNAs (eccDNAs/ecDNAs) exist in tumor and normal cells independently of the chromosome and are essential for oncogene plasticity and drug resistance. Studies have confirmed that there are many eccDNAs/ecDNAs in maternal plasma derived from the fetus. Fetal growth restriction (FGR) is a pregnancy-related disease associated with high newborn morbidity and mortality. However, the characteristics and nature of eccDNAs/ecDNAs in FGR are poorly understood. This study aims to deconstruct the properties and potential functions of eccDNAs/ecDNAs in FGR. We performed circle-seq to identify the expression profile of eccDNAs/ecDNAs, analyzed by bioinformatics, and verified by real-time Polymerase Chain Reaction (PCR) combined with southern blot in FGR compared with the normal groups. A total of 45,131 eccDNAs/ecDNAs (including 2,118 unique ones) were identified, which had significantly higher abundance in FRG group than in normal group, and was bimodal in length, peaking at ~146bp and ~340bp, respectively. Gestational age may be one independent factor affecting the production of eccDNAs/ecDNAs, most of which come from genomic regions with high gene density, with a 4~12bp repeat around the junction, and their origin had a certain genetic preference. In addition, some of the host-genes overlapped with non-coding RNAs (ncRNAs) partially or even completely. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that host-genes on the differentially expressed eccDNAs/ecDNAs (DEEECs/DEECs) were mainly enriched in immune-related functions and pathways. The presence of some ecDNAs were verified, and whose variability were consistent with the circle-seq results. We identified and characterized eccDNAs/ecDNAs in placentas with FGR, and elucidated the formation mechanisms and the networks with ncRNAs, which provide a new vision for the screening of new biomarkers and therapeutic targets for FGR.

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Section: Discussionmentioning

confidence: 71%

Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction

Yang

Huang

et al. 2021

Front. Immunol.

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“…Several papers highlighted the relevant role of EVs released by decidual macrophages in the cross talk between fetal and maternal cells during pregnancy showing that the physiological balance between M1 and M2 phenotypes is essential during pregnancy (63). In this setting, miRNAs play a key role in human placental development at different levels during gestation, where dysregulation of miRNAs in both placenta and blood has been associated with maternal exposures to several toxicants (64).…”

Section: Discussionmentioning

confidence: 99%

2,2’4,4’-Tetrabromodiphenyl Ether (PBDE-47) Modulates the Intracellular miRNA Profile, sEV Biogenesis and Their miRNA Cargo Exacerbating the LPS-Induced Pro-Inflammatory Response in THP-1 Macrophages

Longo

Adamo

et al. 2021

Front. Immunol.

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The 2,2’4,4’-tetrabromodiphenyl ether (PBDE-47) is one of the most prominent PBDE congeners detected in the environment and in animal and human tissues. Animal model experiments suggested the occurrence of PBDE-induced immunotoxicity leading to different outcomes and recently we demonstrated that this substance can impair macrophage and basophil activities. In this manuscript, we decided to further examine the effects induced by PBDE-47 treatment on innate immune response by looking at the intracellular expression profile of miRNAs as well as the biogenesis, cargo content and activity of human M(LPS) macrophage cell-derived small extracellular vesicles (sEVs). Microarray and in silico analysis demonstrated that PBDE-47 can induce some epigenetic effects in M(LPS) THP-1 cells modulating the expression of a set of intracellular miRNAs involved in biological pathways regulating the expression of estrogen-mediated signaling and immune responses with particular reference to M1/M2 differentiation. In addition to the cell-intrinsic modulation of intracellular miRNAs, we demonstrated that PBDE-47 could also interfere with the biogenesis of sEVs increasing their number and selecting a de novo population of sEVs. Moreover, PBDE-47 induced the overload of specific immune related miRNAs in PBDE-47 derived sEVs. Finally, culture experiments with naïve M(LPS) macrophages demonstrated that purified PBDE-47 derived sEVs can modulate macrophage immune response exacerbating the LPS-induced pro-inflammatory response inducing the overexpression of the IL-6 and the MMP9 genes. Data from this study demonstrated that PBDE-47 can perturb the innate immune response at different levels modulating the intracellular expression of miRNAs but also interfering with the biogenesis, cargo content and functional activity of M(LPS) macrophage cell-derived sEVs.

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“…When nicotine crosses through the placenta, binds to a-subunit of nAChRs, and activates them, then nAChRs increase intracellular calcium [Ca 2+ ] i that leads to intracellular signaling disconnection, apoptotic pathways activation, or organelle actions disruption which causes ROS production and then OS happens [ [44] , [45] , [46] ]. Also nicotine could change the expression of some placental microRNAs [ 47 ] which play several roles in many biological processes such as regulation of trophoblast differentiation, emigration, invasion, programmed cell death and angiogenesis [ 48 ]. Researches demonstrated that ethanol causes a decrease in the size of the zone and degenerative alterations in both labyrinthine and basal zones also interrupt blood flow [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of ethanol and nicotine co-administration on follicular atresia and placental histo-morphology in the first-generation mice pups during intrauterine development and lactation periods

et al. 2021

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Graphical abstract Schematic representation of experimental design in different groups of mothers and offspring. CTL group: control group; Veh group: vehicle group received normal saline; Ni group: nicotine group received 1 mg/kg/day nicotine, subcutaneously; EtOH group: ethanol group received 3 g/kg/day, 20 % v/v ethanol intraperitoneally; Ni + EtOH group: ethanol plus nicotine which received both.

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Placental microRNAs: Responders to environmental chemicals and mediators of pathophysiology of the human placenta

Cited by 33 publications

References 157 publications

Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction

Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction

2,2’4,4’-Tetrabromodiphenyl Ether (PBDE-47) Modulates the Intracellular miRNA Profile, sEV Biogenesis and Their miRNA Cargo Exacerbating the LPS-Induced Pro-Inflammatory Response in THP-1 Macrophages

Effects of ethanol and nicotine co-administration on follicular atresia and placental histo-morphology in the first-generation mice pups during intrauterine development and lactation periods

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