High-throughput miRNA-sequencing of the human placenta: expression throughout gestation

Gonzalez, Tania L.; Eisman, Laura E; Joshi, Nikhil; Flowers, Amy E; Wu, Di; Wang, Yizhou; Santiskulvong, Chintda; Tang, Jie; Buttle, Rae; Sauro, Erica; Clark, Ekaterina L; DiPentino, Rosemarie; Jefferies, Caroline A.; Chan, Jessica; Lin, Yayu; Zhu, Yazhen; Afshar, Yalda; Tseng, Hsian‐Rong; Taylor, Kent D.; Williams, John W; Pisarska, Margareta D.

doi:10.1101/2021.02.04.429392

Cited by 4 publications

(13 citation statements)

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“…We identified the sex specific microRNA signature of the first and third trimester placenta in pregnancies resulting in live births. There were similar numbers of miRNAs expressed in both sexes in each trimester, with similar chromosome distributions and peaks at chromosomes 1, 14, 19, and X as previously described [19, 54-56]. Overall, the majority of miRNA were not sexually dimorphic with 11 differentially expressed miRNAs following multiple comparisons in first and 4 in third trimester placentae, all upregulated in females.…”

Section: Discussionsupporting

confidence: 80%

“…miRNAs generally cause target messenger RNA to be degraded, or prevent translation to protein [13]; small changes in miRNA expression can result in multi-fold changes in gene expression[14]. In the placenta, miRNAs are important as early as trophectoderm development and implantation, some through export in exosomes [15-18], but these miRNA signatures change in the placenta throughout gestation during normal development [19-21]. In addition, there are two large miRNA clusters enriched in placenta, the chromosome 14 miRNA cluster (C14MC) and the chromosome 19 miRNA cluster (C19MC)[22, 23].…”

Section: Introductionmentioning

confidence: 99%

“…C19MC is a large, imprinted, paternally-expressed miRNA cluster whose members have highest expression in placenta and cancer, with relatively weak expression in other tissue[23-28]. In addition, two small clusters on chromosome 13 were recently identified to be uniquely present in the first trimester placenta [19, 29]. miRNAs have been identified in several pregnancy-related diseases, including pre-eclampsia [30-35], fetal growth [35-38], and gestational diabetes [39, 40], all sexually dimorphic pregnancy complications.…”

Section: Introductionmentioning

confidence: 99%

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Sex differences in microRNA expression in first and third trimester human placenta

Flowers

Gonzalez

et al. 2021

Preprint

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Maternal and fetal pregnancy outcomes related to placental function vary based on fetal sex, which may be the result of sexually dimorphic epigenetic regulation of RNA expression. We identified sexually dimorphic miRNA expression throughout gestation in human placentae. Next-generation sequencing was used to identify miRNA expression profiles in first and third trimester uncomplicated pregnancies using tissue obtained at chorionic villous sampling (n=113) and parturition (n=47). Sequencing and differential expression (DE) analysis identified 432 mature miRNAs expressed in the first trimester female, 425 in the first trimester male, 400 in the third trimester female, and 508 in the third trimester male placenta (baseMean >10). Of these, 11 sexually dimorphic (FDR<0.05, baseMean >10) miRNAs were identified in the first and 4 miRNAs were identified in the third trimester, including miR-361-5p, significant in both trimesters, all upregulated in females. Across gestation, 207 miRNAs were DE across gestation, common to both females and males, miR-4483, the most DE across gestation. There were twice as many female-specific differences across gestation as male-specific (44 miRNAs vs 21 miRNAs), indicating that miRNA abundance across human gestation is sexually dimorphic. Pathway enrichment analysis identified significant pathways that were differentially regulated in first and third trimester as well as across gestation. This work provides the normative sex dimorphic miRNA atlas in first and third trimester, as well as the sex independent and sex specific placenta miRNA atlas across gestation which may be used to identify biomarkers of placental function and direct functional studies investigating placental sex differences.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sex differences in microRNA expression in first and third trimester human placenta

Flowers

Gonzalez

et al. 2021

Preprint

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“…Although few studies have reported miRNAs associated with pregnancy, these were mainly restricted to miRNAs from known pregnancy-associated clusters in the placenta, or were conducted using maternal plasma/serum in late pregnancy [6,12,23]. To our knowledge, this is the first study characterizing the whole maternal plasmatic microtranscriptome at first trimester of pregnancy, and identifying miRNAs associated with pregnancy and their temporal variation within the first weeks of pregnancy.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have demonstrated that miRNAs from clusters on chromosome 14 (C14MC) and chromosome 19 (C19MC and miR-371-3) measured both in placenta tissue and plasma are associated with pregnancy and differentially expressed between placentas from normal and complicated pregnancies [10][11][12]. These miRNAs are contained in regions involved in embryonic development and the regulation of cellular differentiation.…”

Section: Introductionmentioning

confidence: 99%

Human plasma pregnancy-associated miRNAs and their temporal variation within the first trimester of pregnancy

Légaré

Clément

Desgagné

et al. 2022

Reprod Biol Endocrinol

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Background During pregnancy, maternal metabolism undergoes substantial changes to support the developing fetus. Such changes are finely regulated by different mechanisms carried out by effectors such as microRNAs (miRNAs). These small non-coding RNAs regulate numerous biological functions, mostly through post-transcriptional repression of gene expression. miRNAs are also secreted in circulation by numerous organs, such as the placenta. However, the complete plasmatic microtranscriptome of pregnant women has still not been fully described, although some miRNA clusters from the chromosome 14 (C14MC) and the chromosome 19 (C19MC and miR-371-3 cluster) have been proposed as being specific to pregnancy. Our aims were thus to describe the plasma microtranscriptome during the first trimester of pregnancy, by assessing the differences with non-pregnant women, and how it varies between the 4th and the 16th week of pregnancy. Methods Plasmatic miRNAs from 436 pregnant (gestational week 4 to 16) and 15 non-pregnant women were quantified using Illumina HiSeq next-generation sequencing platform. Differentially abundant miRNAs were identified using DESeq2 package (FDR q-value ≤ 0.05) and their targeted biological pathways were assessed with DIANA-miRpath. Results A total of 2101 miRNAs were detected, of which 191 were differentially abundant (fold change < 0.05 or > 2, FDR q-value ≤ 0.05) between pregnant and non-pregnant women. Of these, 100 miRNAs were less and 91 miRNAs were more abundant in pregnant women. Additionally, the abundance of 57 miRNAs varied according to gestational age at first trimester, of which 47 were positively and 10 were negatively associated with advancing gestational age. miRNAs from the C19MC were positively associated with both pregnancy and gestational age variation during the first trimester. Biological pathway analysis revealed that these 191 (pregnancy-specific) and 57 (gestational age markers) miRNAs targeted genes involved in fatty acid metabolism, ECM-receptor interaction and TGF-beta signaling pathways. Conclusion We have identified circulating miRNAs specific to pregnancy and/or that varied with gestational age in first trimester. These miRNAs target biological pathways involved in lipid metabolism as well as placenta and embryo development, suggesting a contribution to the maternal metabolic adaptation to pregnancy and fetal growth.

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Sex differences in microRNA expression in first and third trimester human placenta

Flowers

Gonzalez

Joshi

et al. 2021

Biology of Reproduction

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Maternal and fetal pregnancy outcomes related to placental function vary based on fetal sex, which may be due to sexually dimorphic epigenetic regulation of RNA expression. We identified sexually dimorphic miRNA expression throughout gestation in human placentae. Next-generation sequencing identified miRNA expression profiles in first and third trimester uncomplicated pregnancies using tissue obtained at chorionic villous sampling (n = 113) and parturition (n = 47). Sequencing analysis identified 986 expressed mature miRNAs from female and male placentae at first and third trimester (baseMean>10). Of these, 11 sexually dimorphic (FDR < 0.05) miRNAs were identified in the first and 4 in the third trimester, all upregulated in females, including miR-361-5p, significant in both trimesters. Sex-specific analyses across gestation identified 677 differentially expressed (DE) miRNAs at FDR < 0.05 and baseMean>10, with 508 DE miRNAs in common between female-specific and male-specific analysis (269 upregulated in first trimester, 239 upregulated in third trimester). Of those, miR-4483 had the highest fold changes across gestation. There were 62.5% more female exclusive differences with fold change>2 across gestation than male exclusive (52 miRNAs vs 32 miRNAs), indicating miRNA expression across human gestation is sexually dimorphic. Pathway enrichment analysis identified significant pathways that were differentially regulated in first and third trimester as well as across gestation. This work provides the normative sex dimorphic miRNA atlas in first and third trimester, as well as the sex-independent and sex-specific placenta miRNA atlas across gestation, which may be used to identify biomarkers of placental function and direct functional studies investigating placental sex differences.

show abstract

High-throughput miRNA-sequencing of the human placenta: expression throughout gestation

Cited by 4 publications

References 83 publications

Sex differences in microRNA expression in first and third trimester human placenta

Sex differences in microRNA expression in first and third trimester human placenta

Human plasma pregnancy-associated miRNAs and their temporal variation within the first trimester of pregnancy

Sex differences in microRNA expression in first and third trimester human placenta

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