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Application of Nutraceuticals in Pregnancy Complications: Does Epigenetics Play a Role?

  • Luís Fernando Schütz
  • Jomer Bernardo
  • Minh Le
  • Tincy Thomas
  • Chau Nguyen
  • Diana Zapata
  • Hitaji Sanford
  • John D. Bowman
  • Brett M. Mitchell
  • Mahua ChoudhuryEmail author
Reference work entry

Abstract

Nutraceuticals provide the prevention or treatment of diseases through dietary supplementation. These become especially important during pregnancy to prevent disorders secondary to nutrient deficiency. In the light of research accomplished in the recent years, it is now established that maternal nutrition affects pregnancy outcomes and disorders through epigenetics, which are heritable gene expression modifications that occur without a change in the DNA sequence. The most studied epigenetic modifications are DNA methylation, histone modifications, and small noncoding RNAs (microRNAs). Recent research has started to unveil how nutraceuticals may prevent pregnancy complications such as preeclampsia, intrauterine growth restriction (IUGR), preterm delivery, and miscarriage through epigenetic mechanisms.

Keywords

Nutraceuticals Pregnancy Epigenetics Methylation Histones MicroRNAs Omega-3 Vitamin D Folic acid Preeclampsia Intrauterine growth restriction 

List of Abbreviations

CYP27B1

Cytochrome P450 family 27 subfamily B member 1

CYP24A1

Cytochrome P450 family 24 subfamily B member 1

DHA

Docosahexaenoic acid

DNMTs

DNA methyltransferases

EPA

Eicosapentaenoic acid

HATs

Histone acetyltransferases

HDACs

Histone deacetylases

HMTs

Histone methyltransferases

IUGR

Intrauterine growth restriction

LDL

Low density lipoprotein

PPARγ

Peroxisome proliferator-activated receptor gamma

PTH

Parathyroid hormone

RXR

Retinoid X receptor

SAH

S-adenosylhomocysteine

SAM

S-adenosylmethionine

Setd8

SET domain containing (lysine methyltransferase) 8

TET

Ten-eleven translocation

UTRs

Untranslated regions

UVB

Ultraviolet B

VDRE

Vitamin D response element

Notes

Acknowledgments

Mahua Choudhury is supported by Morris L Lichtenstein Jr Medical Research Foundation for diabetes and obesity research and Texas A & M Health Science Center Faculty Development Fund

References

  1. Agrawal S, Fledderjohann J, Vellakkal S, Stuckler D (2015) Adequately diversified dietary intake and iron and folic acid supplementation during pregnancy is associated with reduced occurrence of symptoms suggestive of pre-eclampsia or eclampsia in Indian women. PLoS One 10(3):e0119120.  https://doi.org/10.1371/journal.pone.0119120CrossRefPubMedPubMedCentralGoogle Scholar
  2. Al-Dughaishi T, Nikolic D, Zadjali F, Al-Hashmi K, Al-Waili K, Rizzo M et al (2016) Nutraceuticals as lipid-lowering treatment in pregnancy and their effects on the metabolic syndrome. Curr Pharm Biotechnol 17(7):614–623CrossRefGoogle Scholar
  3. Amhed R, Dunford J, Mehran R, Robson S, Kunadian V (2014) Pre-eclampsia and future cardiovascular risk among women: a review. J Am Coll Cardiol 63(18):1815–1822CrossRefGoogle Scholar
  4. Anderson CM, Ralph JL, Johnson L, Scheett A, Wright ML, Taylor JY et al (2015) First trimester vitamin D status and placental epigenomics in preeclampsia among Northern Plains primiparas. Life Sci 129:10–15CrossRefGoogle Scholar
  5. Armelagos GJ (2014) Brain evolution, the determinates of food choice, and the omnivore’s dilemma. Crit Rev Food Sci Nutr 54(10):1330–1341CrossRefGoogle Scholar
  6. Aubard Y, Darodes N, Cantaloube M (2000) Hyperhomocysteinemia and pregnancy – review of our present understanding and therapeutic implications. Eur J Obstet Gynecol Reprod Biol 93(2):157–165CrossRefGoogle Scholar
  7. Baker BC, Mackie FL, Lean SC, Greenwood SL, Heazell AE, Forbes K et al (2017) Placental dysfunction is associated with altered microRNA expression in pregnant women with low folate status. Mol Nutr Food Res.  https://doi.org/10.1002/mnfr.201600646
  8. Balogun OO, da Silva LK, Ota E, Takemoto Y, Rumbold A, Takegata M et al (2016) Vitamin supplementation for preventing miscarriage. Cochrane Database Syst Rev 5:CD004073.  https://doi.org/10.1002/14651858.CD004073.pub4CrossRefGoogle Scholar
  9. Bouillon R, Van Cromphaut S, Carmeliet G (2003) Intestinal calcium absorption: molecular vitamin D mediated mechanisms. J Cell Biochem 88(2):332–339CrossRefGoogle Scholar
  10. Brower V (1998) Nutraceuticals: poised for a healthy slice of the healthcare market? Nat Biotechnol 16(8):728–731CrossRefGoogle Scholar
  11. Brown SB, Reeves KW, Bertone-Johnson ER (2014) Maternal folate exposure in pregnancy and childhood asthma and allergy: a systematic review. Nutr Rev 72(1):55–64CrossRefGoogle Scholar
  12. Calvo MS, Whiting SJ, Barton CN (2005) Vitamin D intake: a global perspective of current status. J Nutr 135(2):310–316CrossRefGoogle Scholar
  13. Cetin I, Giovannini N, Alvino G, Agostoni C, Riva E, Giovannini M et al (2002) Intrauterine growth restriction is associated with changes in polyunsaturated fatty acid fetal-maternal relationships. Pediatr Res 52(5):750–755CrossRefGoogle Scholar
  14. Chango A, Pogribny IP (2015) Considering maternal dietary modulators for epigenetic regulation and programming of the fetal epigenome. Forum Nutr 7(4):2748–2770Google Scholar
  15. Choi SW, Mason JB (2002) Folate status: effects on pathways of colorectal carcinogenesis. J Nutr 132(Suppl 8):2413S–2418SCrossRefGoogle Scholar
  16. Christakos S, Dhawan P, Peng X, Obukhov AG, Nowycky MC, Benn BS et al (2007) New insights into the function and regulation of vitamin D target proteins. Steroid Biochem Mol Biol 103(3–5):405–410CrossRefGoogle Scholar
  17. Dang J, Arcot J, Shrestha A (2000) Folate retention in selected processed legumes. Food Chem 68(3):295–298CrossRefGoogle Scholar
  18. DeLuca HF, Zierold C (1998) Mechanisms and functions of vitamin D. Nutr Rev 56(2 Pt 2):S4–10; discussion S 54–75Google Scholar
  19. De-Regil LM, Palacios C, Lombardo LK, Pena-Rosas JP (2016) Vitamin D supplementation for women during pregnancy. Cochrane Database Syst Rev 1:CD008873.  https://doi.org/10.1002/14651858.CD008873.pub3CrossRefGoogle Scholar
  20. DeVilbiss EA, Gardner RM, Newschaffer CJ, Lee BK (2015) Maternal folate status as a risk factor for autism spectrum disorders: a review of existing evidence. Br J Nutr 114(5):663–672CrossRefGoogle Scholar
  21. Dhobale M, Joshi S (2012) Altered maternal micronutrients (folic acid, vitamin B(12)) and omega 3 fatty acids through oxidative stress may reduce neurotrophic factors in preterm pregnancy. J Matern Fetal Neonatal Med 25(4):317–323CrossRefGoogle Scholar
  22. Enquobahrie DA, Williams MA, Qiu C, Siscovick DS, Sorensen TK (2011) Global maternal early pregnancy peripheral blood mRNA and miRNA expression profiles according to plasma 25-hydroxyvitamin D concentrations. J Matern Fetal Neonatal Med 24(8):1002–1012CrossRefGoogle Scholar
  23. Fetahu IS, Hobaus J, Kallay E (2014) Vitamin D and the epigenome. Front Physiol 5:164CrossRefGoogle Scholar
  24. Fleet JC, Schoch RD (2010) Molecular mechanisms for regulation of intestinal calcium absorption by vitamin D and other factors. Crit Rev Clin Lab Sci 47(4):181–195CrossRefGoogle Scholar
  25. Friso S, Udali S, De Santis D, Choi SW (2016) One-carbon metabolism and epigenetics. Mol Asp Med.  https://doi.org/10.1016/j.mam.2016.11.007
  26. Gage TB, O’Connor K (1994) Nutrition and the variation in level and age patterns of mortality. Hum Biol 66(1):77–103PubMedGoogle Scholar
  27. Garcia BA, Luka Z, Loukachevitch LV, Bhanu NV, Wagner C (2016) Folate deficiency affects histone methylation. Med Hypotheses 88:63–67CrossRefGoogle Scholar
  28. Gladyshev MI, Sushchik NN, Makhutova ON (2013) Production of EPA and DHA in aquatic ecosystems and their transfer to the land. Prostaglandins Other Lipid Mediat 107:117–126CrossRefGoogle Scholar
  29. Goh YI, Koren G (2008) Folic acid in pregnancy and fetal outcomes. J Obstet Gynaecol 28(1):3–13CrossRefGoogle Scholar
  30. Goyal R, Zhang L, Blood AB, Baylink DJ, Longo LD, Oshiro B et al (2014) Characterization of an animal model of pregnancy-induced vitamin D deficiency due to metabolic gene dysregulation. Am J Physiol Endocrinol Metab 306(3):E256–E266CrossRefGoogle Scholar
  31. Gul K, Singh AK, Jabeen R (2016) Nutraceuticals and functional foods: the foods for the future world. Crit Rev Food Sci Nutr 56(16):2617–2627CrossRefGoogle Scholar
  32. Handy DE, Castro R, Loscalzo J (2011) Epigenetic modifications: basic mechanisms and role in cardiovascular disease. Circulation 123(19):2145–2156CrossRefGoogle Scholar
  33. Hardy G (2000) Nutraceuticals and functional foods: introduction and meaning. Nutrition 16(7–8):688–689CrossRefGoogle Scholar
  34. He L, Hannon GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5(7):522–531CrossRefGoogle Scholar
  35. Huppertz B, Weiss G, Moser G (2014) Trophoblast invasion and oxygenation of the placenta: measurements versus presumptions. J Reprod Immunol 101–102:74–79CrossRefGoogle Scholar
  36. Jones ML, Mark PJ, Waddell BJ (2014) Maternal dietary omega-3 fatty acids and placental function. Reproduction 147(5):R143–R152CrossRefGoogle Scholar
  37. Joss-Moore LA, Wang Y, Baack ML, Yao J, Norris AW, Yu X et al (2010) IUGR decreases PPARgamma and SETD8 expression in neonatal rat lung and these effects are ameliorated by maternal DHA supplementation. Early Hum Dev 86(12):785–791CrossRefGoogle Scholar
  38. Kalani A, Kamat PK, Givvimani S, Brown K, Metreveli N, Tyagi SC et al (2014) Nutri-epigenetics ameliorates blood-brain barrier damage and neurodegeneration in hyperhomocysteinemia: role of folic acid. J Mol Neurosci 52(2):202–215CrossRefGoogle Scholar
  39. Kalra EK (2003) Nutraceutical – definition and introduction. AAPS PharmSci 5(3):E25CrossRefGoogle Scholar
  40. Kar S, Wong M, Rogozinska E, Thangaratinam S (2016) Effects of omega-3 fatty acids in prevention of early preterm delivery: a systematic review and meta-analysis of randomized studies. Eur J Obstet Gynecol Reprod Biol 198:40–46CrossRefGoogle Scholar
  41. Kemse NG, Kale AA, Joshi SR (2014) A combined supplementation of omega-3 fatty acids and micronutrients (folic acid, vitamin B12) reduces oxidative stress markers in a rat model of pregnancy induced hypertension. PLoS One 9(11):e111902.  https://doi.org/10.1371/journal.pone.0111902CrossRefPubMedPubMedCentralGoogle Scholar
  42. Konings EJ, Roomans HH, Dorant E, Goldbohm RA, Saris WH, van den Brandt PA (2001) Folate intake of the Dutch population according to newly established liquid chromatography data for foods. Am J Clin Nutr 73(4):765–776CrossRefGoogle Scholar
  43. Kulkarni A, Dangat K, Kale A, Sable P, Chavan-Gautam P, Joshi S (2011) Effects of altered maternal folic acid, vitamin B12 and docosahexaenoic acid on placental global DNA methylation patterns in Wistar rats. PLoS One 6(3):e17706.  https://doi.org/10.1371/journal.pone.0017706CrossRefPubMedPubMedCentralGoogle Scholar
  44. Lewis S, Lucas RM, Halliday J, Ponsonby AL (2010) Vitamin D deficiency and pregnancy: from preconception to birth. Mol Nutr Food Res 54(8):1092–1102PubMedGoogle Scholar
  45. Lillycrop KA, Phillips ES, Jackson AA, Hanson MA, Burdge GC (2005) Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J Nutr 135(6):1382–1386CrossRefGoogle Scholar
  46. Lucock M (2000) Folic acid: nutritional biochemistry, molecular biology, and role in disease processes. Mol Genet Metab 71(1–2):121–138CrossRefGoogle Scholar
  47. Mentch SJ, Locasale JW (2016) One-carbon metabolism and epigenetics: understanding the specificity. Ann N Y Acad Sci 1363:91–98CrossRefGoogle Scholar
  48. Mouillet JF, Chu T, Sadovsky Y (2011) Expression patterns of placental microRNAs. Birth Defects Res A Clin Mol Teratol 91(8):737–743CrossRefGoogle Scholar
  49. Mozurkewich EL, Klemens C (2012) Omega-3 fatty acids and pregnancy: current implications for practice. Curr Opin Obstet Gynecol 24(2):72–77CrossRefGoogle Scholar
  50. Novakovic B, Sibson M, Ng HK, Manuelpillai U, Rakyan V, Down T et al (2009) Placenta-specific methylation of the vitamin D 24-hydroxylase gene: implications for feedback autoregulation of active vitamin D levels at the fetomaternal interface. J Biol Chem 284(22):14838–14848CrossRefGoogle Scholar
  51. Omotayo MO, Dickin KL, O’Brien KO, Neufeld LM, De Regil LM, Stoltzfus RJ (2016) Calcium supplementation to prevent preeclampsia: translating guidelines into practice in low-income countries. Adv Nutr 7(2):275–278CrossRefGoogle Scholar
  52. Ortega FJ, Cardona-Alvarado MI, Mercader JM, Moreno-Navarrete JM, Moreno M, Sabater M et al (2015) Circulating profiling reveals the effect of a polyunsaturated fatty acid-enriched diet on common microRNAs. J Nutr Biochem 26(10):1095–1101CrossRefGoogle Scholar
  53. Perez-Lopez FR (2007) Vitamin D: the secosteroid hormone and human reproduction. Gynecol Endocrinol 23(1):13–24CrossRefGoogle Scholar
  54. Peterson CL, Laniel MA (2004) Histones and histone modifications. Curr Biol 14(14):R546–R551CrossRefGoogle Scholar
  55. Poniedzialek-Czajkowska E, Mierzynski R, Kimber-Trojnar Z, Leszczynska-Gorzelak B, Oleszczuk J (2014) Polyunsaturated fatty acids in pregnancy and metabolic syndrome: a review. Curr Pharm Biotechnol 15(1):84–99CrossRefGoogle Scholar
  56. Saini RK, Nile SH, Keum Y (2016) Folates: chemistry, analysis, occurrence, biofortification and bioavailability. Food Res Int 89:1–13CrossRefGoogle Scholar
  57. Scorletti E, Byrne CD (2013) Omega-3 fatty acids, hepatic lipid metabolism, and nonalcoholic fatty liver disease. Annu Rev Nutr 33:231–248CrossRefGoogle Scholar
  58. Shahbazian N, Jafari RM, Haghnia S (2016) The evaluation of serum homocysteine, folic acid, and vitamin B12 in patients complicated with preeclampsia. Electron Physician 8(10):3057–3061CrossRefGoogle Scholar
  59. Stea TH, Johansson M, Jägerstad M, Frølich W (2006) Retention of folates in cooked, stored and reheated peas, broccoli and potatoes for use in modern large-scale service systems. Food Chem 101:1095–1107CrossRefGoogle Scholar
  60. Sutton AL, MacDonald PN (2003) Vitamin D: more than a “bone-a-fide” hormone. Mol Endocrinol 17(5):777–791CrossRefGoogle Scholar
  61. Tammen SA, Friso S, Choi SW (2013) Epigenetics: the link between nature and nurture. Mol Asp Med 34(4):753–764CrossRefGoogle Scholar
  62. Tokunaga M, Takahashi T, Singh RB, De Meester F, Wilson DW (2013) Nutrition and epigenetics. Med Epigenet 1:70–77CrossRefGoogle Scholar
  63. Tsukiyama T, Wu C (1997) Chromatin remodeling and transcription. Curr Opin Genet Dev 7(2):182–191CrossRefGoogle Scholar
  64. Wiktorowska-Owczarek A, Berezinska M, Nowak JZ (2015) PUFAs: structures, metabolism and functions. Adv Clin Exp Med 24(6):931–941CrossRefGoogle Scholar
  65. Winkels RM, Brouwer IA, Siebelink E, Katan MB, Verhoef P (2007) Bioavailability of food folates is 80% of that of folic acid. Am J Clin Nutr 85(2):465–473CrossRefGoogle Scholar
  66. Wolffe AP, Matzke MA (1999) Epigenetics: regulation through repression. Science 286(5439):481–486CrossRefGoogle Scholar
  67. Zhang MX, Pan GT, Guo JF, Li BY, Qin LQ, Zhang ZL (2015) Vitamin D deficiency increases the risk of gestational diabetes mellitus: a meta-analysis of observational studies. Forum Nutr 7(10):8366–8375Google Scholar
  68. Zhong Y, Tuuli M, Odibo AO (2010) First-trimester assessment of placenta function and the prediction of preeclampsia and intrauterine growth restriction. Prenat Diagn 30(4):293–308PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Luís Fernando Schütz
    • 1
  • Jomer Bernardo
    • 2
  • Minh Le
    • 2
  • Tincy Thomas
    • 1
  • Chau Nguyen
    • 2
  • Diana Zapata
    • 1
  • Hitaji Sanford
    • 2
  • John D. Bowman
    • 2
  • Brett M. Mitchell
    • 3
  • Mahua Choudhury
    • 1
    Email author
  1. 1.Department of Pharmaceutical SciencesIrma Lerma Rangel College of Pharmacy, Texas A&M Health Science CenterCollege StationUSA
  2. 2.Texas A&M Irma Lerma Rangel College of PharmacyKingsvilleUSA
  3. 3.Texas A&M, Department of Medical PhysiologyCollege StationUSA

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