Download PDF
AJP Rep 2016; 06(04): e430-e435
DOI: 10.1055/s-0036-1597652
Case Report
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Placental microRNA Expression Is Not Altered by Maternal Obesity and Fetal Overgrowth

Neda Ghaffari
1   Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, Maternal and Child Health Research Program, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
,
Samuel Parry
1   Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, Maternal and Child Health Research Program, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
,
Michal A. Elovitz
1   Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, Maternal and Child Health Research Program, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
,
Celeste P. Durnwald
1   Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, Maternal and Child Health Research Program, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
› Author Affiliations
Further Information

Publication History

15 September 2016

15 November 2016

Publication Date:
30 December 2016 (online)

Also available at
   Permissions and Reprints

Abstract

Objective The epigenetic mechanisms underlying fetal metabolic programming are poorly understood. We studied whether obesity is associated with alterations in placental miRNA expression.

Study Design A cross-sectional study was performed, including (1) normal-weight women (BMI 20–24.9 kg/m2) and normal-birth-weight (BW) infants (2,700–3,500 g) (n = 20), (2) normal-weight and macrosomic infants (BW ≥ 4,000 g) (n = 10), (3) obese (BMI ≥ 35 kg/m2) and normal BW infants (n = 16), and (4) obese and macrosomic infants (n = 10). All had term deliveries (37–41 weeks) and normal glucose tolerance (1 hour GCT < 7.2 mmol/L [130 mg/dL]). The expression of 5,639 placental miRNAs was assessed using miRNA microarray. Differential miRNA expression was determined using two-way ANOVA and pairwise contrasts, with the Benjamini-Hochberg (BH) correction. MiRNAs with Z-scores ≥ 2 and false discovery rate (FDR) < 20% were considered significant.

Results Principal components analysis demonstrated similar global miRNA expression profiles among groups. Of 5,639 miRNAs, only 5 were significantly different between obese and controls, which were not validated by quantitative polymerase reaction.

Conclusion There was no difference in placental miRNA expression associated with obesity or overgrowth. Aberrant placental miRNA expression is an unlikely mechanism underlying fetal metabolic programming related to maternal obesity.

Keywords

obesity - fetal metabolic programming - microRNA - macrosomia

Note

The Maternal and Child Health Research Program within the Department of Obstetrics and Gynecology at the University of Pennsylvania Health System provided financial support for this research.


 

  • References

  • 1 American College of Obstetricians and Gynecologists. ACOG Committee opinion no. 549: obesity in pregnancy. Obstet Gynecol 2013; 121 (1) 213-217
    CrossrefPubMedGoogle Scholar
  • 2 Catalano PM, Hauguel-De Mouzon S. Is it time to revisit the Pedersen hypothesis in the face of the obesity epidemic?. Am J Obstet Gynecol 2011; 204 (6) 479-487
    CrossrefPubMedGoogle Scholar
  • 3 Barker DJ, Gluckman PD, Godfrey KM, Harding JE, Owens JA, Robinson JS. Fetal nutrition and cardiovascular disease in adult life. Lancet 1993; 341 (8850): 938-941
    CrossrefPubMedGoogle Scholar
  • 4 Mamun AA, Hayatbakhsh MR, O'Callaghan M, Williams G, Najman J. Early overweight and pubertal maturation—pathways of association with young adults' overweight: a longitudinal study. Int J Obes 2009; 33 (1) 14-20
    CrossrefPubMedGoogle Scholar
  • 5 Wen X, Triche EW, Hogan JW, Shenassa ED, Buka SL. Prenatal factors for childhood blood pressure mediated by intrauterine and/or childhood growth?. Pediatrics 2011; 127 (3) e713-e721
    CrossrefPubMedGoogle Scholar
  • 6 Lau C, Rogers JM, Desai M, Ross MG. Fetal programming of adult disease: implications for prenatal care. Obstet Gynecol 2011; 117 (4) 978-985
    CrossrefPubMedGoogle Scholar
  • 7 Boney CM, Verma A, Tucker R, Vohr BR. Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 2005; 115 (3) e290-e296
    CrossrefPubMedGoogle Scholar
  • 8 Kappil M, Chen J. Environmental exposures in utero and microRNA. Curr Opin Pediatr 2014; 26 (2) 243-251
    CrossrefPubMedGoogle Scholar
  • 9 Williams AE. Functional aspects of animal microRNAs. Cell Mol Life Sci 2008; 65 (4) 545-562
    CrossrefPubMedGoogle Scholar
  • 10 Zhang J, Zhang F, Didelot X , et al. Maternal high fat diet during pregnancy and lactation alters hepatic expression of insulin like growth factor-2 and key microRNAs in the adult offspring. BMC Genomics 2009; 10: 478 DOI: 10.1186/1471-2164-10-478.
    CrossrefPubMedGoogle Scholar
  • 11 Zhao Z, Moley KH, Gronowski AM. Diagnostic potential for miRNAs as biomarkers for pregnancy-specific diseases. Clin Biochem 2013; 46 (10–11): 953-960
    CrossrefPubMedGoogle Scholar
  • 12 Luo R, Shao X, Xu P , et al. MicroRNA-210 contributes to preeclampsia by downregulating potassium channel modulatory factor 1. Hypertension 2014; 64 (4) 839-845
    CrossrefPubMedGoogle Scholar
  • 13 Kleinrouweler CE, van Uitert M, Moerland PD, Ris-Stalpers C, van der Post JA, Afink GB. Differentially expressed genes in the pre-eclamptic placenta: a systematic review and meta-analysis. PLoS One 2013; 8 (7) e68991
    CrossrefPubMedGoogle Scholar
  • 14 Pineles BL, Romero R, Montenegro D , et al. Distinct subsets of microRNAs are expressed differentially in the human placentas of patients with preeclampsia. Am J Obstet Gynecol 2007; 196 (3) 261.e1-261.e6
    CrossrefPubMedGoogle Scholar
  • 15 Maccani MA, Padbury JF, Marsit CJ. miR-16 and miR-21 expression in the placenta is associated with fetal growth. PLoS One 2011; 6 (6) e21210
    CrossrefPubMedGoogle Scholar
  • 16 Mayor-Lynn K, Toloubeydokhti T, Cruz AC, Chegini N. Expression profile of microRNAs and mRNAs in human placentas from pregnancies complicated by preeclampsia and preterm labor. Reprod Sci 2011; 18 (1) 46-56
    CrossrefPubMedGoogle Scholar
  • 17 Donovan L, Hartling L, Muise M, Guthrie A, Vandermeer B, Dryden DM. Screening tests for gestational diabetes: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 2013; 159 (2) 115-122
    CrossrefPubMedGoogle Scholar
  • 18 Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan M. A United States national reference for fetal growth. Obstet Gynecol 1996; 87 (2) 163-168
    CrossrefPubMedGoogle Scholar
  • 19 Pavlidis P, Li Q, Noble WS. The effect of replication on gene expression microarray experiments. Bioinformatics 2003; 19 (13) 1620-1627
    CrossrefPubMedGoogle Scholar
  • 20 Burton GJ, Sebire NJ, Myatt L , et al. Optimising sample collection for placental research. Placenta 2014; 35 (1) 9-22
    CrossrefPubMedGoogle Scholar
  • 21 Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25 (4) 402-408
    CrossrefPubMedGoogle Scholar
  • 22 Challier JC, Basu S, Bintein T , et al. Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta. Placenta 2008; 29 (3) 274-281
    CrossrefPubMedGoogle Scholar
  • 23 Maloyan A, Muralimanoharan S, Huffman S , et al. Identification and comparative analyses of myocardial miRNAs involved in the fetal response to maternal obesity. Physiol Genomics 2013; 45 (19) 889-900
    CrossrefPubMedGoogle Scholar
  • 24 Nicholas LM, Rattanatray L, MacLaughlin SM , et al. Differential effects of maternal obesity and weight loss in the periconceptional period on the epigenetic regulation of hepatic insulin-signaling pathways in the offspring. FASEB J 2013; 27 (9) 3786-3796
    CrossrefPubMedGoogle Scholar
  • 25 Yan X, Huang Y, Zhao JX , et al. Maternal obesity downregulates microRNA let-7g expression, a possible mechanism for enhanced adipogenesis during ovine fetal skeletal muscle development. Int J Obes 2013; 37 (4) 568-575
    CrossrefPubMedGoogle Scholar
  • 26 Ghaffari N, Parry S, Elovitz MA, Durnwald CP. The effect of an obesogenic maternal environment on expression of fetal umbilical cord blood miRNA. Reprod Sci 2014; DOI: 10.1177/1933719114565032.
    PubMedGoogle Scholar
  • 27 Draghici S, Khatri P, Eklund AC, Szallasi Z. Reliability and reproducibility issues in DNA microarray measurements. Trends Genet 2006; 22 (2) 101-109
    CrossrefPubMedGoogle Scholar
  • 28 Gemma C, Sookoian S, Alvariñas J , et al. Maternal pregestational BMI is associated with methylation of the PPARGC1A promoter in newborns. Obesity (Silver Spring) 2009; 17 (5) 1032-1039
    CrossrefPubMedGoogle Scholar
  • 29 Perkins E, Murphy SK, Murtha AP , et al. Insulin-like growth factor 2/H19 methylation at birth and risk of overweight and obesity in children. J Pediatr 2012; 161 (1) 31-39
    CrossrefPubMedGoogle Scholar
  • 30 Sookoian S, Gianotti TF, Burgueño AL, Pirola CJ. Fetal metabolic programming and epigenetic modifications: a systems biology approach. Pediatr Res 2013; 73 (4 Pt 2): 531-542
    CrossrefPubMedGoogle Scholar
  • 31 Bodnar LM, Siega-Riz AM, Simhan HN, Diesel JC, Abrams B. The impact of exposure misclassification on associations between prepregnancy BMI and adverse pregnancy outcomes. Obesity (Silver Spring) 2010; 18 (11) 2184-2190
    CrossrefPubMedGoogle Scholar
  • 32 Rossi AC, Mullin P, Prefumo F. Prevention, management, and outcomes of macrosomia: a systematic review of literature and meta-analysis. Obstet Gynecol Surv 2013; 68 (10) 702-709
    CrossrefPubMedGoogle Scholar