Hostname: page-component-cd9895bd7-gxg78 Total loading time: 0 Render date: 2024-12-26T08:04:47.126Z Has data issue: false hasContentIssue false
  • English
  • Français

Placental lipoprotein lipase DNA methylation levels are associated with gestational diabetes mellitus and maternal and cord blood lipid profiles

Published online by Cambridge University Press:  12 February 2014

A. A. Houde ,
J. St-Pierre ,
M. F. Hivert ,
J. P. Baillargeon ,
P. Perron ,
D. Gaudet ,
D. Brisson  and
L. Bouchard
A. A. Houde
Affiliation:
Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Qc, Canada ECOGENE-21 and Clinical Research Center and Lipid Clinic, Chicoutimi Hospital, Saguenay, Qc, Canada
J. St-Pierre
Affiliation:
ECOGENE-21 and Clinical Research Center and Lipid Clinic, Chicoutimi Hospital, Saguenay, Qc, Canada Department of Pediatric, CSSS de Chicoutimi, Saguenay, Qc, Canada
M. F. Hivert
Affiliation:
Department of Medicine, Division of Endocrinology, Université de Sherbrooke, Sherbrooke, Qc, Canada General Medicine Division, Massachusetts General Hospital, Boston, MA, USA
J. P. Baillargeon
Affiliation:
Department of Medicine, Division of Endocrinology, Université de Sherbrooke, Sherbrooke, Qc, Canada
P. Perron
Affiliation:
ECOGENE-21 and Clinical Research Center and Lipid Clinic, Chicoutimi Hospital, Saguenay, Qc, Canada Department of Medicine, Division of Endocrinology, Université de Sherbrooke, Sherbrooke, Qc, Canada
D. Gaudet
Affiliation:
ECOGENE-21 and Clinical Research Center and Lipid Clinic, Chicoutimi Hospital, Saguenay, Qc, Canada Department of Medicine, Université de Montréal, Montréal, Qc, Canada
D. Brisson
Affiliation:
ECOGENE-21 and Clinical Research Center and Lipid Clinic, Chicoutimi Hospital, Saguenay, Qc, Canada Department of Medicine, Université de Montréal, Montréal, Qc, Canada
L. Bouchard*
Affiliation:
Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Qc, Canada ECOGENE-21 and Clinical Research Center and Lipid Clinic, Chicoutimi Hospital, Saguenay, Qc, Canada
*
*Address for correspondence: L. Bouchard, PhD, MBA, Laboratoire ECOGENE-21, Pavillon des Augustines-AUG-5–06, CHAU régional de Chicoutimi, Saguenay, Canada G1K 7P4. (Email: luigi.bouchard@usherbrooke.ca)
Get access Rights & Permissions [Opens in a new window]

Abstract

Placental lipoprotein lipase (LPL) is crucial for placental lipid transfer. Impaired LPL gene expression and activity were reported in pregnancies complicated by gestational diabetes mellitus (GDM) and intra-uterine growth restriction. We hypothesized that placental LPL DNA methylation is altered by maternal metabolic status and could contribute to fetal programming. The objective of this study was thus to assess whether placental LPL DNA methylation is associated with GDM and both maternal and newborn lipid profiles. Placenta biopsies were sampled at delivery from 126 women including 27 women with GDM diagnosed following a post 75 g-oral glucose tolerance test (OGTT) between weeks 24 and 28 of gestation. Placental LPL DNA methylation and expression levels were determined using bisulfite pyrosequencing and quantitative real-time PCR, respectively. DNA methylation levels within LPL proximal promoter region (CpG1) and intron 1 CpG island (CpGs 2 and 3) were lower in placenta of women with GDM. DNA methylation levels at LPL-CpG1 and CpG3 were also negatively correlated with maternal glucose (2-h post OGTT; r=–0.22; P=0.02) and HDL-cholesterol levels (third trimester of pregnancy; r=–0.20; p=0.03), respectively. Moreover, we report correlation between LPL-CpG2 DNA methylation and cord blood lipid profile. DNA methylation levels within intron 1 CpG island explained up to 26% (r⩽–0.51; P<0.001) of placental LPL mRNA expression variance. Overall, we showed that maternal metabolic profile is associated with placental LPL DNA methylation dysregulation. Our results suggest that site-specific LPL epipolymorphisms in the placenta are possibly functional and could potentially be involved in determining the future metabolic health of the newborn.

Keywords

fetal programmingHDL-chyperglycemia
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 5 , Issue 2 , April 2014 , pp. 132 - 141
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Woollett, LA. Fetal lipid metabolism. Front Biosci. 2001; 6, D536–D545.CrossRefGoogle ScholarPubMed
2. Gil-Sanchez, A, Koletzko, B, Larque, E. Current understanding of placental fatty acid transport. Curr Opin Clin Nutr Metab Care. 2012; 15, 265–272.CrossRefGoogle ScholarPubMed
3. Larque, E, Demmelmair, H, Gil-Sanchez, A, et al. Placental transfer of fatty acids and fetal implications. Am J Clin Nutr. 2011; 94, 1908S–1913S.CrossRefGoogle ScholarPubMed
4. McCoy, MG, Sun, GS, Marchadier, D, et al. Characterization of the lipolytic activity of endothelial lipase. J Lipid Res. 2002; 43, 921–929.CrossRefGoogle ScholarPubMed
5. Radaelli, T, Lepercq, J, Varastehpour, A, et al. Differential regulation of genes for fetoplacental lipid pathways in pregnancy with gestational and type 1 diabetes mellitus. Am J Obstet Gynecol. 2009; 201, e1–e10.CrossRefGoogle ScholarPubMed
6. Tabano, S, Alvino, G, Antonazzo, P, et al. Placental LPL gene expression is increased in severe intrauterine growth-restricted pregnancies. Pediatr Res. 2006; 59, 250–253.CrossRefGoogle ScholarPubMed
7. Gauster, M, Hiden, U, Blaschitz, A, et al. Dysregulation of placental endothelial lipase and lipoprotein lipase in intrauterine growth-restricted pregnancies. J Clin Endocrinol Metab. 2007; 92, 2256–2263.CrossRefGoogle ScholarPubMed
8. Magnusson-Olsson, AL, Hamark, B, Ericsson, A, et al. Gestational and hormonal regulation of human placental lipoprotein lipase. J Lipid Res. 2006; 47, 2551–2561.CrossRefGoogle ScholarPubMed
9. Chernausek, SD. Update: consequences of abnormal fetal growth. J Clin Endocrinol Metab. 2012; 97, 689–695.CrossRefGoogle ScholarPubMed
10. Barker, DJ. Adult consequences of fetal growth restriction. Clin Obstet Gynecol. 2006; 49, 270–283.CrossRefGoogle ScholarPubMed
11. Bestor, TH. The DNA methyltransferases of mammals. Hum Mol Gen. 2000; 9, 2395–2402.CrossRefGoogle ScholarPubMed
12. Bird, AP, Wolffe, AP. Methylation-induced repression – belts, braces, and chromatin. Cell. 1999; 99, 451–454.CrossRefGoogle ScholarPubMed
13. Tobi, EW, Lumey, LH, Talens, RP, et al. DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Gen. 2009; 18, 4046–4053.CrossRefGoogle ScholarPubMed
14. Heijmans, BT, Tobi, EW, Lumey, LH, Slagboom, PE. The epigenome: archive of the prenatal environment. Epigenetics. 2009; 4, 526–531.CrossRefGoogle ScholarPubMed
15. Yuen, RK, Avila, L, Penaherrera, MS, et al. Human placental-specific epipolymorphism and its association with adverse pregnancy outcomes. PloS One. 2009; 4, e7389.CrossRefGoogle ScholarPubMed
16. Turan, N, Ghalwash, MF, Katari, S, et al. DNA methylation differences at growth related genes correlate with birth weight: a molecular signature linked to developmental origins of adult disease? BMC Med genomics. 2012; 5, 10.CrossRefGoogle ScholarPubMed
17. Bouchard, L, Thibault, S, Guay, SP, et al. Leptin gene epigenetic adaptation to impaired glucose metabolism during pregnancy. Diabetes Care. 2010; 33, 2436–2441.CrossRefGoogle ScholarPubMed
18. Bouchard, L, Hivert, MF, Guay, SP, et al. Placental adiponectin gene DNA methylation levels are associated with mothers' blood glucose concentration. Diabetes. 2012; 61, 1272−12780.CrossRefGoogle ScholarPubMed
19. Lohman, TG RAaMR. Anthropometric Standardization Reference Manual. 1988. Human Kinetics Books: Champaign, IL.Google Scholar
20. Friedewald, WT, Levy, RI, Fredrickson, DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972; 18, 499–502.CrossRefGoogle ScholarPubMed
21. Matthews, DR, Hosker, JP, Rudenski, AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28, 412–419.CrossRefGoogle ScholarPubMed
22. Heding, LG. Radioimmunological determination of human C-peptide in serum. Diabetologia. 1975; 11, 541–548.CrossRefGoogle ScholarPubMed
23. Ruchat, SM, Houde, AA, Voisin, G, et al. Gestational diabetes mellitus epigenetically affects genes predominantly involved in metabolic diseases. Epigenetics. 2013; 8, 935–943.CrossRefGoogle ScholarPubMed
24. Dejeux, E, El abdalaoui, H, Gut, IG, Tost, J. Identification and quantification of differentially methylated loci by the pyrosequencing technology. Methods Mol Biol. 2009; 507, 189–205.CrossRefGoogle ScholarPubMed
25. Meller, M, Vadachkoria, S, Luthy, DA, Williams, MA. Evaluation of housekeeping genes in placental comparative expression studies. Placenta. 2005; 26, 601–607.CrossRefGoogle ScholarPubMed
26. Murthi, P, Fitzpatrick, E, Borg, AJ, et al. GAPDH 18S rRNA and YWHAZ are suitable endogenous reference genes for relative gene expression studies in placental tissues from human idiopathic fetal growth restriction. Placenta. 2008; 29, 798–801.CrossRefGoogle ScholarPubMed
27. Drewlo, S, Levytska, K, Kingdom, J. Revisiting the housekeeping genes of human placental development and insufficiency syndromes. Placenta. 2012; 33, 952–954.CrossRefGoogle ScholarPubMed
28. 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, 402–408.CrossRefGoogle ScholarPubMed
29. Olsen, IE, Groveman, SA, Lawson, ML, Clark, RH, Zemel, BS. New intrauterine growth curves based on United States data. Pediatrics. 2010; 125, e214–e224.CrossRefGoogle ScholarPubMed
30. Dube, E, Gravel, A, Martin, C, et al. Modulation of fatty acid transport and metabolism by maternal obesity in the human full-term placenta. Biol Reprod. 2012; 87, 1–11.CrossRefGoogle ScholarPubMed
31. Magnusson, AL, Waterman, IJ, Wennergren, M, Jansson, T, Powell, TL. Triglyceride hydrolase activities and expression of fatty acid binding proteins in the human placenta in pregnancies complicated by intrauterine growth restriction and diabetes. J Clin Endocrinol Metab. 2004; 89, 4607–4614.CrossRefGoogle ScholarPubMed
32. Walsh, JM, Mahony, R, Byrne, J, Foley, M, McAuliffe, FM. The association of maternal and fetal glucose homeostasis with fetal adiposity and birthweight. Eur J Obstet Gynecol Reprod Biol. 2011; 159, 338–341.CrossRefGoogle ScholarPubMed
33. Deierlein, AL, Siega-Riz, AM, Chantala, K, Herring, AH. The association between maternal glucose concentration and child BMI at age 3 years. Diabetes Care. 2011; 34, 480–484.CrossRefGoogle ScholarPubMed
34. El Hajj, N, Pliushch, G, Schneider, E, et al. Metabolic programming of MEST DNA methylation by intrauterine exposure to gestational diabetes mellitus. Diabetes. 2013; 62, 1320–1328.CrossRefGoogle ScholarPubMed
35. Houde, AA, Guay, SP, Desgagne, V, et al. Adaptations of placental and cord blood ABCA1 DNA methylation profile to maternal metabolic status. Epigenetics. 2013; 8, 1289–1302.CrossRefGoogle ScholarPubMed
36. Kitajima, M, Oka, S, Yasuhi, I, et al. Maternal serum triglyceride at 24–32 weeks’ gestation and newborn weight in nondiabetic women with positive diabetic screens. Obstet Gynecol. 2001; 97, 776–780.CrossRefGoogle ScholarPubMed
37. Di Cianni, G, Miccoli, R, Volpe, L, et al. Maternal triglyceride levels and newborn weight in pregnant women with normal glucose tolerance. Diabetic Med. 2005; 22, 21–25.CrossRefGoogle ScholarPubMed
38. Zeljkovic, A, Vekic, J, Spasic, S, et al. Changes in LDL and HDL subclasses in normal pregnancy and associations with birth weight, birth length and head circumference. Matern Child Health J. 2013; 17, 556–565.Google Scholar
39. Mazza, A, Bossone, E, Mazza, F, Distante, A. Reduced serum homocysteine levels in type 2 diabetes. Nutr Metab Cardiovasc Dis. 2005; 15, 118–124.CrossRefGoogle ScholarPubMed
40. Chiang, EP, Wang, YC, Chen, WW, Tang, FY. Effects of insulin and glucose on cellular metabolic fluxes in homocysteine transsulfuration, remethylation, S-adenosylmethionine synthesis, and global deoxyribonucleic acid methylation. J Clin Endocrinol Metab. 2009; 94, 1017–1025.CrossRefGoogle ScholarPubMed
41. Kim, ES, Isoda, F, Kurland, I, Mobbs, CV. Glucose-induced metabolic memory in Schwann cells: prevention by PPAR agonists. Endocrinology. 2013.CrossRefGoogle Scholar
42. Vickers, KC, Palmisano, BT, Shoucri, BM, Shamburek, RD, Remaley, AT. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol. 2011; 13, 423–433.CrossRefGoogle ScholarPubMed
43. Denis, H, Ndlovu, MN, Fuks, F. Regulation of mammalian DNA methyltransferases: a route to new mechanisms. EMBO Rep. 2011; 12, 647–656.CrossRefGoogle ScholarPubMed
44. Schoonjans, K, Peinado-Onsurbe, J, Lefebvre, AM, et al. PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J. 1996; 15, 5336–5348.CrossRefGoogle Scholar
45. Wang, H, Eckel, RH. Lipoprotein lipase: from gene to obesity. Am J Physiol Endocrinol Metab. 2009; 297, E271–E288.CrossRefGoogle ScholarPubMed
46. Liu, D, Deschamps, A, Korach, KS, Murphy, E. Estrogen-enhanced gene expression of lipoprotein lipase in heart is antagonized by progesterone. Endocrinology. 2008; 149, 711–716.CrossRefGoogle ScholarPubMed
47. Guay, SP, Brisson, D, Lamarche, B, et al. DNA methylation variations at CETP and LPL gene promoter loci: new molecular biomarkers associated with blood lipid profile variability. Atherosclerosis. 2013.CrossRefGoogle ScholarPubMed
48. Ma, RC, Chan, JC, Tam, WH, Hanson, MA, Gluckman, PD. Gestational diabetes, maternal obesity, and the NCD burden. Clin Obstet Gynecol. 2013; 56, 633–641.CrossRefGoogle ScholarPubMed
49. Marco, LJ, McCloskey, K, Vuillermin, PJ, et al. Cardiovascular disease risk in the offspring of diabetic women: the impact of the intrauterine environment. Exp Diabetes Res. 2012; 2012, 565160.CrossRefGoogle ScholarPubMed
50. Weaver, IC, Cervoni, N, Champagne, FA, et al. Epigenetic programming by maternal behavior. Nat Neurosci. 2004; 7, 847–854.CrossRefGoogle ScholarPubMed
51. Kent, WJ, Sugnet, CW, Furey, TS, et al. The human genome browser at UCSC. Genome Res. 2002; 12, 996–1006.CrossRefGoogle ScholarPubMed