Placental expression of miR-21-5p, miR-210-3p and miR-141-3p: relation to human fetoplacental growth.
Journal
European journal of clinical nutrition
ISSN: 1476-5640
Titre abrégé: Eur J Clin Nutr
Pays: England
ID NLM: 8804070
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
05
02
2021
accepted:
21
09
2021
revised:
06
09
2021
pubmed:
7
10
2021
medline:
14
5
2022
entrez:
6
10
2021
Statut:
ppublish
Résumé
Dysregulation of microRNAs (miRNAs) and their target genes in placental tissue is associated with foetal growth restriction. We aimed to evaluate associations of placental miR-21-5p, miR-141-3p and miR-210-3p expression with maternal, placental and newborn parameters and with placental expression of their potential target genes PTEN, VEGF, FLT and ENG in a set of well-characterized small- (SGA) and appropriate- (AGA) for gestational age full-term singleton pregnancies. Placental samples (n = 80) from 26 SGA and 54 AGA were collected from full-term singleton pregnancies. Placental transcript abundances of miR-21-5p, miR-141-3p and miR-210-3p were assessed after normalization to a reference miRNA, mir-16-5p by real-time quantitative PCR. Placental transcript abundances of PTEN, VEGF, FLT and ENG were assessed after normalizing to a panel of reference genes. Placental miR-21-5p transcript abundance was negatively associated with placental weight (n = 80, r = -0.222, P = 0.047) and this association was specific to the AGA births (n = 54, r = -0.292, P = 0.032). Placental transcript abundances of miR-210-3p and miR-141-3p were not associated with placental weight or birth weight in all 80 births. However, placental miR-210-3p transcript abundance was positively associated with birth weight specifically in the SGA births (n = 26, r = 0.449, P = 0.021). Placental transcript abundance of miR-21-5p was negatively associated with PTEN transcript abundance (Spearman's ρ = -0.245, P = 0.028) while that of miR-141-3p was positively associated with FLT (Spearman's ρ = 0.261, P = 0.019) and ENG (Spearman's ρ = 0.259, P = 0.020) transcript abundances in all 80 births. We conclude that placental miR-21-5p and miR-210-3p may be involved in fetoplacental growth. However, this regulation is unlikely to be mediated through placental expression of PTEN, VEGF, FLT or ENG.
Sections du résumé
BACKGROUND/OBJECTIVES
Dysregulation of microRNAs (miRNAs) and their target genes in placental tissue is associated with foetal growth restriction. We aimed to evaluate associations of placental miR-21-5p, miR-141-3p and miR-210-3p expression with maternal, placental and newborn parameters and with placental expression of their potential target genes PTEN, VEGF, FLT and ENG in a set of well-characterized small- (SGA) and appropriate- (AGA) for gestational age full-term singleton pregnancies.
SUBJECTS/METHODS
Placental samples (n = 80) from 26 SGA and 54 AGA were collected from full-term singleton pregnancies. Placental transcript abundances of miR-21-5p, miR-141-3p and miR-210-3p were assessed after normalization to a reference miRNA, mir-16-5p by real-time quantitative PCR. Placental transcript abundances of PTEN, VEGF, FLT and ENG were assessed after normalizing to a panel of reference genes.
RESULTS
Placental miR-21-5p transcript abundance was negatively associated with placental weight (n = 80, r = -0.222, P = 0.047) and this association was specific to the AGA births (n = 54, r = -0.292, P = 0.032). Placental transcript abundances of miR-210-3p and miR-141-3p were not associated with placental weight or birth weight in all 80 births. However, placental miR-210-3p transcript abundance was positively associated with birth weight specifically in the SGA births (n = 26, r = 0.449, P = 0.021). Placental transcript abundance of miR-21-5p was negatively associated with PTEN transcript abundance (Spearman's ρ = -0.245, P = 0.028) while that of miR-141-3p was positively associated with FLT (Spearman's ρ = 0.261, P = 0.019) and ENG (Spearman's ρ = 0.259, P = 0.020) transcript abundances in all 80 births.
CONCLUSION
We conclude that placental miR-21-5p and miR-210-3p may be involved in fetoplacental growth. However, this regulation is unlikely to be mediated through placental expression of PTEN, VEGF, FLT or ENG.
Identifiants
pubmed: 34611295
doi: 10.1038/s41430-021-01017-x
pii: 10.1038/s41430-021-01017-x
doi:
Substances chimiques
MIRN141 microRNA, human
0
MIRN21 microRNA, human
0
MIRN210 microRNA, human
0
MicroRNAs
0
Vascular Endothelial Growth Factor A
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
730-738Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Lee ACC, Katz J, Blencowe H, Cousens S, Kozuki N, Vogel JP, et al. National and regional estimates of term and preterm babies born small for gestational age in 138 low-income and middle-income countries in 2010. Lancet Glob Heal. 2013;1:e26–36.
doi: 10.1016/S2214-109X(13)70006-8
Hong YH, Chung S. Small for gestational age and obesity related comorbidities. Ann Pediatr Endocrinol Metab. 2018;23:4–8.
pubmed: 29609443
pmcid: 5894558
doi: 10.6065/apem.2018.23.1.4
Bernstein PS, Divon MY. Etiologies of fetal growth restriction. Clin Obstet Gynecol. 1997;40:723–9.
pubmed: 9429786
doi: 10.1097/00003081-199712000-00006
Krishna U, Bhalerao S. Placental insufficiency and fetal growth restriction. J Obstet Gynecol India. 2011;61:505–11.
doi: 10.1007/s13224-011-0092-x
Gude NM, Roberts CT, Kalionis B, King RG. Growth and function of the normal human placenta. Thromb Res. 2004;114:397–407.
pubmed: 15507270
doi: 10.1016/j.thromres.2004.06.038
Cindrova-Davies T, Herrera EA, Niu Y, Kingdom J, Giussani DA, Burton GJ. Reduced cystathionine γ-lyase and increased miR-21 expression are associated with increased vascular resistance in growth-restricted pregnancies: Hydrogen sulfide as a placental vasodilator. Am J Pathol. 2013;182:1448–58.
pubmed: 23410520
doi: 10.1016/j.ajpath.2013.01.001
Hromadnikova I, Kotlabova K, Ondrackova M, Pirkova P, Kestlerova A, Novotna V, et al. Expression Profile of C19MC microRNAs in Placental Tissue in Pregnancy-Related Complications. DNA Cell Biol. 2015;34:437–57.
pubmed: 25825993
pmcid: 4486149
doi: 10.1089/dna.2014.2687
Higashijima A, Miura K, Mishima H, Kinoshita A, Jo O, Abe S, et al. Characterization of placenta-specific microRNAs in fetal growth restriction pregnancy. Prenat Diagn. 2013;33:214–22.
pubmed: 23354729
doi: 10.1002/pd.4045
Tang Q, Wu W, Xu X, Huang L, Gao Q, Chen H, et al. miR-141 contributes to fetal growth restriction by regulating PLAG1 expression. PLoS One. 2013;8:e58737.
pubmed: 23554918
pmcid: 3598866
doi: 10.1371/journal.pone.0058737
Felekkis K, Touvana E, Stefanou C, Deltas C. MicroRNAs: a newly described class of encoded molecules that play a role in health and disease. Hippokratia. 2010;14:236–40.
pubmed: 21311629
pmcid: 3031315
Lee DC, Romero R, Kim JS, Tarca AL, Montenegro D, Pineles BL, et al. 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;179:590–602.
pubmed: 21801864
pmcid: 3160082
doi: 10.1016/j.ajpath.2011.04.035
Guo L, Tsai SQ, Hardison NE, James AH, Motsinger-Reif AA, Thames B, et al. Differentially expressed microRNAs and affected biological pathways revealed by modulated modularity clustering (MMC) analysis of human preeclamptic and IUGR placentas. Placenta. 2013;34:599–605.
pubmed: 23639576
pmcid: 3677766
doi: 10.1016/j.placenta.2013.04.007
Östling H, Kruse R, Helenius G, Lodefalk M. Placental expression of microRNAs in infants born small for gestational age. Placenta. 2019;81:46–53.
pubmed: 31138431
doi: 10.1016/j.placenta.2019.05.001
Maccani MA, Padbury JF, Marsit CJ. miR-16 and miR-21 expression in the placenta is associated with fetal growth. PLoS One. 2011;6:e21210.
pubmed: 21698265
pmcid: 3115987
doi: 10.1371/journal.pone.0021210
Fasanaro P, D’Alessandra Y, Di Stefano V, Melchionna R, Romani S, Pompilio G, et al. MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand ephrin-A3. J Biol Chem. 2008;283:15878–83.
pubmed: 18417479
pmcid: 3259646
doi: 10.1074/jbc.M800731200
Anton L, Olarerin-George AO, Schwartz N, Srinivas S, Bastek J, Hogenesch JB, et al. miR-210 inhibits trophoblast invasion and is a serum biomarker for preeclampsia. Am J Pathol. 2013;183:1437–45.
pubmed: 24035613
pmcid: 3814521
doi: 10.1016/j.ajpath.2013.07.021
Zhang Y, Fei M, Xue G, Zhou Q, Jia Y, Li L, et al. Elevated levels of hypoxia-inducible microRNA-210 in pre-eclampsia: new insights into molecular mechanisms for the disease. J Cell Mol Med. 2012;16:249–59.
pubmed: 21388517
pmcid: 3823289
doi: 10.1111/j.1582-4934.2011.01291.x
Morales-Prieto DM, Chaiwangyen W, Ospina-Prieto S, Schneider U, Herrmann J, Gruhn B, et al. MicroRNA expression profiles of trophoblastic cells. Placenta. 2012;33:725–34.
pubmed: 22721760
doi: 10.1016/j.placenta.2012.05.009
Stepan H, Krämer T, Faber R. Brief report: Maternal plasma concentrations of soluble endoglin in pregnancies with intrauterine growth restriction. J Clin Endocrinol Metab. 2007;92:2831–4.
pubmed: 17426082
doi: 10.1210/jc.2006-2774
Romero R, Nien JK, Espinoza J, Todem D, Fu W, Chung H, et al. A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for. J Matern Neonatal Med. 2008;21:9–23.
doi: 10.1080/14767050701830480
Åsvold OB, Vatten LJ, Romundstad PR, Jenum PA, Karumanchi SA, Anne E. Angiogenic factors in maternal circulation and the risk of severe fetal growth restriction. Am J Epidemiol. 2011;173:630–9.
pubmed: 21317220
doi: 10.1093/aje/kwq373
Thamotharan S, Chu A, Kempf K, Janzen C, Grogan T, Elashoff DA, et al. Differential microRNA expression in human placentas of term intra-uterine growth restriction that regulates target genes mediating angiogenesis and amino acid transport. PLoS One. 2017;12:e0176493.
pubmed: 28463968
pmcid: 5413012
doi: 10.1371/journal.pone.0176493
Franz F, Edgar E, Albert-Georg L, Axel B. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39:175.
doi: 10.3758/BF03193146
Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. World Heal Organ Tech Rep Ser. 1995;854:1–452.
Soncin F, Khater M, To C, Pizzo D, Farah O, Wakeland A, et al. Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development. Development. 2018;145:dev156273.
pubmed: 29361559
pmcid: 5825847
doi: 10.1242/dev.156273
Raman K, Wang H, Troncone MJ, Khan WI, Pare G, Terry J. Overlap chronic placental inflammation is associated with a unique gene expression pattern. Kanellopoulos-Langevin C, editor. PLoS One. 2015;10:e0133738.
pubmed: 26207633
pmcid: 4514672
doi: 10.1371/journal.pone.0133738
Mukhopadhyay A, Ravikumar G, Dwarkanath P, Meraaj H, Thomas A, Crasta J, et al. Placental expression of the insulin receptor binding protein GRB10: relation to human fetoplacental growth and fetal gender. Placenta. 2015;36:1225–30.
pubmed: 26390806
doi: 10.1016/j.placenta.2015.09.006
Mukhopadhyay A, Ravikumar G, Meraaj H, Dwarkanath P, Thomas A, Crasta J, et al. Placental expression of DNA methyltransferase 1 (DNMT1): gender-specific relation with human placental growth. Placenta. 2016;48:119–25.
pubmed: 27871462
doi: 10.1016/j.placenta.2016.09.013
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods. 2001;25:402–8.
pubmed: 11846609
doi: 10.1006/meth.2001.1262
Wang D, Na Q, Song WW, Song GY. Altered expression of miR-518b and miR-519a in the placenta is associated with low fetal birth weight. Am J Perinatol. 2014;31:729–34.
pubmed: 24683074
doi: 10.1055/s-0033-1361832
Solayman MHM, Langaee T, Patel A, El-Wakeel L, El-Hamamsy M, Badary O, et al. identification of suitable endogenous normalizers for qRT-PCR analysis of plasma microRNA expression in essential hypertension. Mol Biotechnol. 2016;58:179–87.
pubmed: 26798072
pmcid: 4758859
doi: 10.1007/s12033-015-9912-z
Bryzgunova OE, Zaripov MM, Skvortsova TE, Lekchnov EA, Grigor’eva AE, Zaporozhchenko IA, et al. Comparative study of extracellular vesicles from the urine of healthy individuals and prostate cancer patients. Carter DRF, editor. PLoS One. 2016;11:e0157566.
pubmed: 27305142
pmcid: 4909321
doi: 10.1371/journal.pone.0157566
Lange T, Stracke S, Rettig R, Lendeckel U, Kuhn J, Schlüter R, et al. Identification of miR-16 as an endogenous reference gene for the normalization of urinary exosomal miRNA expression data from CKD patients. Ray RB, editor. PLoS One. 2017;12:e0183435.
pubmed: 28859135
pmcid: 5578666
doi: 10.1371/journal.pone.0183435
Kochhar P, Dwarkanath P, Ravikumar G, Thomas A, Crasta J, Thomas T, et al. Mukhopadhyay A. Placental expression of RNU44 RNU48 and miR-16-5p: stability and relations with fetoplacental growth. European Journal of Clinical Nutrition. https://doi.org/10.1038/s41430-021-01003-3 .
Mani C, Kochhar P, Ravikumar G, Dwarkanath P, Sheela CN, George S, et al. Placental expression of ENG, VEGF, and FLT: gender-specific associations with maternal vitamin B12 status. Eur J Clin Nutr. 2020;74:176–82.
pubmed: 31209272
doi: 10.1038/s41430-019-0449-2
Jager KJ, Zoccali C, MacLeod A, Dekker FW. Confounding: what it is and how to deal with it. Kidney Int. 2008;73:256–60.
pubmed: 17978811
doi: 10.1038/sj.ki.5002650
Barros FC, de Rabello Neto DL, Villar J, Kennedy SH, Silveira MF, Diaz-Rossello JL, et al. Caesarean sections and the prevalence of preterm and early-term births in Brazil: secondary analyses of national birth registration. BMJ Open. 2018;8:e021538.
pubmed: 30082353
pmcid: 6078248
doi: 10.1136/bmjopen-2018-021538
Smith GCS. A population study of birth weight and the risk of caesarean section: Scotland 1980–1996. BJOG Int J Obstet Gynaecol. 2000;107:740–4.
doi: 10.1111/j.1471-0528.2000.tb13334.x
Parrish KM. Effect of changes in maternal age, parity, and birth weight distribution on primary cesarean delivery rates. JAMA J Am Med Assoc. 1994;271:443–7.
doi: 10.1001/jama.1994.03510300049037
Zhao Z, Moley KH, Gronowski AM. Diagnostic potential for miRNAs as biomarkers for pregnancy-specific diseases. Clin Biochem. 2013;46:953–60.
pubmed: 23396163
doi: 10.1016/j.clinbiochem.2013.01.026
Miura K, Higashijima A, Hasegawa Y, Abe S, Miura S, Kaneuchi M, et al. Circulating levels of maternal plasma cell-free miR-21 are associated with maternal body mass index and neonatal birth weight. Prenat Diagn. 2015;35:509–11.
pubmed: 25273622
doi: 10.1002/pd.4509
Zhang J-T, Cai Q-Y, Ji S-S, Zhang H-X, Wang Y-H, Yan H-T, et al. Decreased miR-143 and increased miR-21 placental expression levels are associated with macrosomia. Mol Med Rep. 2016;13:3273–80.
pubmed: 26934915
doi: 10.3892/mmr.2016.4892
Jiang H, Wu W, Zhang M, Li J, Peng Y, Miao T-T, et al. Aberrant upregulation of miR-21 in placental tissues of macrosomia. J Perinatol. 2014;34:658–63.
pubmed: 24786382
doi: 10.1038/jp.2014.58
Whitehead CL, Teh WT, Walker SP, Leung C, Larmour L, Tong S. Circulating MicroRNAs in maternal blood as potential biomarkers for fetal hypoxia in-utero. PLoS One. 2013;8:e78487.
pubmed: 24282500
pmcid: 3839903
doi: 10.1371/journal.pone.0078487
Chaiwangyen W, Ospina-Prieto S, Photini SM, Schleussner E, Markert UR, Morales-Prieto DM. Dissimilar microRNA-21 functions and targets in trophoblastic cell lines of different origin. Int J Biochem Cell Biol. 2015;68:187–96.
pubmed: 26320576
doi: 10.1016/j.biocel.2015.08.018
Liu ZL, Wang H, Liu J, Wang ZX. MicroRNA-21 (miR-21) expression promotes growth, metastasis, and chemo- or radioresistance in non-small cell lung cancer cells by targeting PTEN. Mol Cell Biochem. 2013;372:35–45.
pubmed: 22956424
doi: 10.1007/s11010-012-1443-3
Lou Y, Yang X, Wang F, Cui Z, Huang Y. MicroRNA-21 promotes the cell proliferation, invasion and migration abilities in ovarian epithelial carcinomas through inhibiting the expression of PTEN protein. Int J Mol Med. 2010;26:819–27.
pubmed: 21042775
doi: 10.3892/ijmm_00000530
Oldham S, Stocker H, Laffargue M, Wittwer F, Wymann M, Hafen E. The Drosophila insulin/IGF receptor controls growth and size by modulating PtdInsP3 levels. Development. 2002;129:4103–9.
pubmed: 12163412
doi: 10.1242/dev.129.17.4103
Garcia-Cao I, Song MS, Hobbs RM, Laurent G, Giorgi C, De Boer VCJ, et al. Systemic elevation of PTEN induces a tumor-suppressive metabolic state. Cell. 2012;149:49–62.
pubmed: 22401813
pmcid: 3319228
doi: 10.1016/j.cell.2012.02.030
Ortega-Molina A, Efeyan A, Lopez-Guadamillas E, Muñoz-Martin M, Gómez-López G, Cañamero M, et al. Pten positively regulates brown adipose function, energy expenditure, and longevity. Cell Metab. 2012;15:382–94.
pubmed: 22405073
doi: 10.1016/j.cmet.2012.02.001
Muralimanoharan S, Guo C, Myatt L, Maloyan A. Sexual dimorphism in miR-210 expression and mitochondrial dysfunction in the placenta with maternal obesity. Int J Obes. 2015;39:1274–81.
doi: 10.1038/ijo.2015.45
Li L, Huang X, He Z, Xiong Y, Fang Q. miRNA-210-3p regulates trophoblast proliferation and invasiveness through fibroblast growth factor 1 in selective intrauterine growth restriction. J Cell Mol Med. 2019;23:4422–33.
pubmed: 30993882
pmcid: 6533475
doi: 10.1111/jcmm.14335
Luo R, Wang Y, Xu P, Cao G, Zhao Y, Shao X, et al. Hypoxia-inducible miR-210 contributes to preeclampsia via targeting thrombospondin type I domain containing 7A. Sci Rep. 2016;6:19588.
pubmed: 26796133
pmcid: 4726282
doi: 10.1038/srep19588
Mutharasan RK, Nagpal V, Ichikawa Y, Ardehali H. microRNA-210 is upregulated in hypoxic cardiomyocytes through Akt- and p53-dependent pathways and exerts cytoprotective effects. Am J Physiol Circ Physiol. 2011;301:H1519–30.
doi: 10.1152/ajpheart.01080.2010
Milovanovic I, Njuieyon F, Deghmoun S, Chevenne D, Levy-Marchal C, Beltrand J. Innate small babies are metabolically healthy children. J Clin Endocrinol Metab. 2012;97:4407–13.
pubmed: 22990095
doi: 10.1210/jc.2012-1993
Mestdagh P, Lefever S, Pattyn F, Ridzon D, Fredlund E, Fieuw A, et al. The microRNA body map: dissecting microRNA function through integrative genomics. Nucleic Acids Res. 2011;39:e136–e136.
pubmed: 21835775
pmcid: 3203610
doi: 10.1093/nar/gkr646
Tan H, Huang S, Zhang Z, Qian X, Sun P, Zhou X. Pan-cancer analysis on microRNA-associated gene activation. EBioMedicine. 2019;43:82–97.
pubmed: 30956173
pmcid: 6557760
doi: 10.1016/j.ebiom.2019.03.082
Pecot CV, Rupaimoole R, Yang D, Akbani R, Ivan C, Lu C, et al. Tumour angiogenesis regulation by the miR-200 family. Nat Commun. 2013;4:1–14.
doi: 10.1038/ncomms3427
Wu D, Chen X, Wang L, Chen F, Cen H, Shi L. Hypoxia-induced microRNA-141 regulates trophoblast apoptosis, invasion, and vascularization by blocking CXCL12β/CXCR2/4 signal transduction. Biomed Pharmacother. 2019;116:108836.
pubmed: 31004838
doi: 10.1016/j.biopha.2019.108836
Chim SSC, Shing TKF, Hung ECW, Leung T-Y, Lau T-K, Chiu RWK, et al. Detection and characterization of placental microRNAs in maternal plasma. Clin Chem. 2008;54:482–90.
pubmed: 18218722
doi: 10.1373/clinchem.2007.097972
Gunel T, Hosseini MK, Gumusoglu E, Kisakesen HI, Benian A, Aydinli K. Expression profiling of maternal plasma and placenta microRNAs in preeclamptic pregnancies by microarray technology. Placenta. 2017;52:77–85.
pubmed: 28454701
doi: 10.1016/j.placenta.2017.02.019
Guo Y, Xiao P, Lei S, Deng F, Xiao GG, Liu Y, et al. How is mRNA expression predictive for protein expression? A correlation study on human circulating monocytes. Acta Biochim Biophys Sin (Shanghai). 2008;40:426–36.
doi: 10.1111/j.1745-7270.2008.00418.x
Williams RL, Creasy RK, Cunningham GC, Hawes WE, Norris FD, Tashiro M. Fetal growth and perinatal viability in California. Obstet Gynecol 1982;59:624–32.
pubmed: 7070736
Pölzlberger E, Hartmann B, Hafner E, Stümpflein I, Kirchengast S. Maternal height and pre-pregnancy weight status are associated with fetal growth patterns and newborn size. J Biosoc Sci 2017;49:392–407.
pubmed: 27692008
doi: 10.1017/S0021932016000493
Zeve D, Regelmann MO, Holzman IR, Rapaport R. Small at birth, but how small? the definition of SGA revisited. Horm Res Paediatr. 2016;86:357–60.
pubmed: 27685026
doi: 10.1159/000449275
Janssen AB, Tunster SJ, Savory N, Holmes A, Beasley J, Parveen SAR, et al. Placental expression of imprinted genes varies with sampling site and mode of delivery. Placenta. 2015;36:790–5.
pubmed: 26162698
pmcid: 4535278
doi: 10.1016/j.placenta.2015.06.011