Skip to main content Accessibility help
×
×
Home

Placental imprinted gene expression mediates the effects of maternal psychosocial stress during pregnancy on fetal growth

  • L. Lambertini (a1) (a2), Q. Li (a1), Y. Ma (a1), W. Zhang (a3), K. Hao (a4), C. Marsit (a5), J. Chen (a1) and Y. Nomura (a1) (a3)...

Abstract

Imprinted genes uniquely drive and support fetoplacental growth by controlling the allocation of maternal resources to the fetus and affecting the newborn’s growth. We previously showed that alterations of the placental imprinted gene expression are associated with suboptimal perinatal growth and respond to environmental stimuli including socio-economic determinants. At the same time, maternal psychosocial stress during pregnancy (MPSP) has been shown to affect fetal growth. Here, we set out to test the hypothesis that placental imprinted gene expression mediates the effects of MPSP on fetal growth in a well-characterized birth cohort, the Stress in Pregnancy (SIP) Study. We observed that mothers experiencing high MPSP deliver infants with lower birthweight (P=0.047). Among the 109 imprinted genes tested, we detected panels of placental imprinted gene expression of 23 imprinted genes associated with MPSP and 26 with birthweight. Among these genes, five imprinted genes (CPXM2, glucosidase alpha acid (GAA), GPR1, SH3 and multiple ankyrin repeat domains 2 (SHANK2) and THSD7A) were common to the two panels. In multivariate analyses, controlling for maternal age and education and gestational age at birth and infant gender, two genes, GAA and SHANK2, each showed a 22% mediation of MPSP on fetal growth. These data provide new insights into the role that imprinted genes play in translating the maternal stress message into a fetoplacental growth pattern.

Copyright

Corresponding author

Address for correspondence: L. Lambertini, Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, One Gustave L. Levi Place, Box 1057, New York, NY, 10029, USA. E-mail: luca.lambertini@mssm.edu

Footnotes

Hide All

Equal contribution

Footnotes

References

Hide All
1. Bressan, FF, De Bem, TH, Perecin, F, et al. Unearthing the roles of imprinted genes in the placenta. Placenta. 2009; 30, 823834.
2. Charalambous, M, da Rocha, ST, Ferguson-Smith, AC. Genomic imprinting, growth control and the allocation of nutritional resources: consequences for postnatal life. Curr Opin Endocrinol Diabetes Obes. 2007; 14, 312.
3. Court, F, Tayama, C, Romanelli, V, et al. Genome-wide parent-of-origin DNA methylation analysis reveals the intricacies of human imprinting and suggests a germline methylation-independent mechanism of establishment. Genome Res. 2014; 24, 554569.
4. Kappil, MA, Green, BB, Armstrong, DA, et al. Placental expression profile of imprinted genes impacts birth weight. Epigenetics. 2015; 10, 842849.
5. Lambertini, L, Marsit, CJ, Sharma, P, et al. Imprinted gene expression in fetal growth and development. Placenta. 2012; 33, 480486.
6. Wolpert, L, Tickle, C, Lawrence, P, et al. Principles of Development, 4th edn, 2010. Oxford University Press: New York, NY.
7. Hu, D, Cross, JC. Development and function of trophoblast giant cells in the rodent placenta. Int J Dev Biol. 2010; 54, 341354.
8. Perry, JK, Lins, RJ, Lobie, PE, Mitchell, MD. Regulation of invasive growth: similar epigenetic mechanisms underpin tumour progression and implantation in human pregnancy. Clin Sci (Lond). 2010; 118, 451457.
9. Schroeder, DI, Blair, JD, Lott, P, et al. The human placenta methylome. Proc Natl Acad Sci U S A. 2013; 110, 60376042.
10. Newman, JR, Ghaemmaghami, S, Ihmels, J, et al. Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise. Nature. 2006; 441, 840846.
11. Zaitoun, I, Downs, KM, Rosa, GJ, Khatib, H. Upregulation of imprinted genes in mice: an insight into the intensity of gene expression and the evolution of genomic imprinting. Epigenetics. 2010; 5, 149158.
12. Kaern, M, Elston, TC, Blake, WJ, Collins, JJ. Stochasticity in gene expression: from theories to phenotypes. Nat Rev Genet. 2005; 6, 451464.
13. Sanchez, A, Choubey, S, Kondev, J. Regulation of noise in gene expression. Ann Rev Biophys. 2013; 42, 469491.
14. Blake, WJ, Kaern, M, Cantor, CR, Collins, JJ. Noise in eukaryotic gene expression. Nature. 2003; 422, 633637.
15. Fraser, HB, Hirsh, AE, Giaever, G, Kumm, J, Eisen, MB. Noise minimization in eukaryotic gene expression. PLoS Biol. 2004; 2, e137.
16. Ruiz, S, Lopez-Contreras, AJ, Gabut, M, et al. Limiting replication stress during somatic cell reprogramming reduces genomic instability in induced pluripotent stem cells. Nat Commun. 2015; 6, 8036.
17. Kappil, MA, Li, Q, Li, A, et al. In utero exposures to environmental organic pollutants disrupt epigenetic marks linked to fetoplacental development. Environ Epigenetics. 2016; 2, dvv013.
18. Chen, J, Li, Q, Rialdi, A, et al. Influences of maternal stress during pregnancy on the epi/genome: comparison of placenta and umbilical cord blood. J Depress Anxiety. 2014; 3, 16.
19. Grote, NK, Bridge, JA, Gavin, AR, et al. A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction. Arch Gen Psychiatry. 2010; 67, 10121024.
20. Loomans, EM, van Dijk, AE, Vrijkotte, TG, et al. Psychosocial stress during pregnancy is related to adverse birth outcomes: results from a large multi-ethnic community-based birth cohort. Eur J Public Health. 2013; 23, 485491.
21. O'Donnell, KJ, Meaney, MJ. Fetal origins of mental health: The developmental origins of health and disease hypothesis. Am J Psychiatry. 2017; 174, 319328.
22. Finik, J, Nomura, Y. Cohort profile: stress in pregnancy (SIP) study. Int J Epidemiol. 2017; 46, 13881388k.
23. Zhang, W, Li, Q, Deyssenroth, M, et al. Timing of prenatal exposure to trauma and altered placental expressions of hypothalamic-pituitary-adrenal axis genes and genes driving neurodevelopment. J Neuroendocrinol. 2018; 30, e12581.
24. Green, BB, Kappil, M, Lambertini, L, et al. Expression of imprinted genes in placenta is associated with infant neurobehavioral development. Epigenetics. 2015; 10, 834841.
25. R Core Team. R: A language and environment for statistical computing. 2013. Retrieved 1 January 2018 from http://www.r-project.org/
26. Waggott, DM. NanoStringNorm: Normalize Nanostring miRNA and mRNA data. R package version 1.1.17. 2014. Retrieved 17 December 2017 from http://cran.r-project.org/packageD=NanoStringNorm.
27. Deyssenroth, MA, Peng, S, Hao, K, et al. Whole-transcriptome analysis delineates the human placenta gene network and its associations with fetal growth. BMC Genomics. 2017; 18, 520.
28. Rasouli, H, Hosseini-Ghazvini, SM, Adibi, H, Khodarahmi, R. Differential alpha-amylase/alpha-glucosidase inhibitory activities of plant-derived phenolic compounds: a virtual screening perspective for the treatment of obesity and diabetes. Food Funct. 2017; 8, 19421954.
29. Zerenturk, EJ, Sharpe, LJ, Ikonen, E, Brown, AJ. Desmosterol and DHCR24: unexpected new directions for a terminal step in cholesterol synthesis. Progress in Lipid Res. 2013; 52, 666680.
30. Crespi, B. Genomic imprinting in the development and evolution of psychotic spectrum conditions. Biol Rev Camb Philos Soc. 2008; 83, 441493.
31. Colland, F, Jacq, X, Trouplin, V, et al. Functional proteomics mapping of a human signaling pathway. Genome Res. 2004; 14, 13241332.
32. Probst, OC, Karayel, E, Schida, N, et al. The mannose 6-phosphate-binding sites of M6P/IGF2R determine its capacity to suppress matrix invasion by squamous cell carcinoma cells. Biochem J. 2013; 451, 9199.
33. Wang, CH, Su, PT, Du, XY, et al. Thrombospondin type I domain containing 7A (THSD7A) mediates endothelial cell migration and tube formation. J Cell Physiol. 2010; 222, 685694.
34. Parisi, T, Beck, AR, Rougier, N, et al. Cyclins E1 and E2 are required for endoreplication in placental trophoblast giant cells. EMBO J. 2003; 22, 47944803.
35. Wu, L, de Bruin, A, Saavedra, HI, et al. Extra-embryonic function of Rb is essential for embryonic development and viability. Nature. 2003; 421, 942947.
36. Ma, S, Chan, YP, Kwan, PS, et al. MicroRNA-616 induces androgen-independent growth of prostate cancer cells by suppressing expression of tissue factor pathway inhibitor TFPI-2. Cancer Res. 2011; 71, 583592.
37. Lieberman, LA, Hunter, CA. Regulatory pathways involved in the infection-induced production of IFN-gamma by NK cells. Microbes Infect. 2002; 4, 15311538.
38. Ernst, MC, Issa, M, Goralski, KB, Sinal, CJ. Chemerin exacerbates glucose intolerance in mouse models of obesity and diabetes. Endocrinology. 2010; 151, 19982007.
39. Monteiro, P, Feng, G. SHANK proteins: roles at the synapse and in autism spectrum disorder. Nat Rev Neurosci. 2017; 18, 147157.
40. Degner, K, Magness, RR, Shah, DM. Establishment of the human uteroplacental circulation: A historical perspective. Reprod Sci. 2017; 24, 753761.
41. Chiba, S. Molecular mechanism in alpha-glucosidase and glucoamylase. Biosci Biotechnol Biochem. 1997; 61, 12331239.
42. Kong, WH, Oh, SH, Ahn, YR, et al. Antiobesity effects and improvement of insulin sensitivity by 1-deoxynojirimycin in animal models. J Agric Food Chem. 2008; 56, 26132619.
43. Liu, Z, Ma, S. Recent advances in synthetic alpha-glucosidase inhibitors. ChemMedChem. 2017; 12, 819829.
44. Leblond, CS, Nava, C, Polge, A, et al. Meta-analysis of SHANK mutations in autism spectrum disorders: a gradient of severity in cognitive impairments. PLoS Genet. 2014; 10, e1004580.
45. Sala, C, Vicidomini, C, Bigi, I, Mossa, A, Verpelli, C. Shank synaptic scaffold proteins: keys to understanding the pathogenesis of autism and other synaptic disorders. J Neurochem. 2015; 135, 849858.
46. Han, K, Holder, JL Jr, Schaaf, CP, et al. SHANK3 overexpression causes manic-like behaviour with unique pharmacogenetic properties. Nature. 2013; 503, 7277.
47. Moessner, R, Marshall, CR, Sutcliffe, JS, et al. Contribution of SHANK3 mutations to autism spectrum disorder. Am J Hum Genet. 2007; 81, 12891297.
48. Grissom, NM, Reyes, TM. Gestational overgrowth and undergrowth affect neurodevelopment: similarities and differences from behavior to epigenetics. Int J Dev Neurosci. 2013; 31, 406414.
49. Pettersson, E, Sjolander, A, Almqvist, C, et al. Birth weight as an independent predictor of ADHD symptoms: a within-twin pair analysis. J Child Psychol Psychiatry. 2015; 56, 453459.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Journal of Developmental Origins of Health and Disease
  • ISSN: 2040-1744
  • EISSN: 2040-1752
  • URL: /core/journals/journal-of-developmental-origins-of-health-and-disease
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords

Type Description Title
PDF
Supplementary materials

Lambertini et al. supplementary material
Figures S1-S5

 PDF (909 KB)
909 KB
PDF
Supplementary materials

Lambertini et al. supplementary material
Tables S1-S16

 PDF (141 KB)
141 KB

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed