The effect of phytochemicals on fetal epigenome

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Hedef Fetus: Yiyeceklerdeki
Fitokimyasalların Potansiyel Bir
Moderatör Olan Epigenoma Etkileri
Dr. Tevfik Yoldemir BSc MSc
Marmara Üniversitesi Tıp Fakültesi
www.yoldemir.com
Impactsof maternal and paternal nutrition on fetal
programming
ANTIOXIDANTS & REDOX SIGNALING Volume 17, Number 2, 2012
One-carbonunit metabolismfor provisionof methyl
donorsin cells
ANTIOXIDANTS & REDOX SIGNALING Volume 17, Number 2, 2012
Rolesof macro- and micro-nutrientsin epigenetics
and physiologicalresponses
ANTIOXIDANTS & REDOX SIGNALING Volume 17, Number 2, 2012
Nutritionalinterventionswith bioactivephytochemicals
• Besides specific nutrients, botanicals have been identified as
possible epigenetic modulators to ameliorate metabolic
syndrome by regulating expression and activity of DNMT, HMT,
HAT, and HDAC.
• Phytochemicals (including epigallocatechingallate, resveratrol,
genistein, curcumin, and isothiocyanates) can interfere with
enzymatic activities of DNMT, Class I, II, IV HDAC, HAT, and Class
III HDAC sirtuins (SIRT), thereby beneficially modulating
inflammatory responses and immunologicalsenescence
ANTIOXIDANTS & REDOX SIGNALING Volume 17, Number 2, 2012
• Plant extracts may also affect interactions among histone
proteins or between nucleosomes and binding factors. Thus,
dietary ingredients in food can be epigenetic medicine to
remedy abnormalities in DNA methylation, histone
modifications, chromatin remodeling, and microRNA patterns
ANTIOXIDANTS & REDOX SIGNALING Volume 17, Number 2, 2012

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Pharmacologicaland nutritionalinterventionsof
epigeneticdefects
ANTIOXIDANTS & REDOX SIGNALING Volume 17, Number 2, 2012
Overviewof epigeneticmechanismsregulatinggene
expression
Seminars in Cancer Biology 40–41 (2016) 82–99
polyphenols
• Phenolic acids that are largely present in berry fruits kiwi,
cherry, apple, pear, chicory and coffee represent a third of the
polyphenolic compounds and are divided into two main
classes:
• hydroxybenzoic acids (C6-C1) (gallic acid, protocatechuic acid,
p-hydroxybenzoic acid) and
• hydroxycinnamic acids (C6-C3) (caffeic acid, chlorogenic acid,
coumaric acid, ferulic acid, sinapic acid);
• Flavonoids (C6–C3–C6) including six subclasses:
• antocyanins, flavanols, flavonols, flavones, flavanones, and
isoflavones;
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
2017, VOL. 57, NO. 12, 2589–2599
polyphenols
• Lignans (C6–C3–C3–C6),found in high concentrations in linseed
and other grains and cereals, largely known for their
phytoesterogenic activity;
• Stilbenes (C6–C2–C6), present in the human diet in low
quantities with resveratrol as the main studied compounds of
these groups and largely detected in grapes and red wine.
• Curcuminoids (C6–C3–C1–C3–C6) constitute another class of
polyphenols, with curcumin being the main molecule that is
found principally in the rhizomes of Curcuma longa.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
2017, VOL. 57, NO. 12, 2589–2599
Polyphenolseffecton epigeneticmechanism
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
2017, VOL. 57, NO. 12, 2589–2599
Epigeneticmodifications
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
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Epigeneticmodifications
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
2017, VOL. 57, NO. 12, 2589–2599
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
2017, VOL. 57, NO. 12, 2589–2599
• Maternal nutrition and
environmental exposure
induce changes in the
epigenome of the
developing fetus.
• The most widely
recognized epigenetic
regulatory mechanisms
include DNA methylation,
histone modifications and
small interfering RNAs
Nutr Rev. 2013 July ; 71(7): 441–457
• Maternal diet during pregnancy, placental insufficiency,
psychosocial characteristics and other factors such as stress,
anxiety and fatigue induce changes in the epigenome of the
embryo.
• Although much effort has been focused on gene-environment
interactions, epigenetic alteration in response to in utero
nutritional and environmental factors also deregulates histone
modifications, microRNAs and alters the CpG methylation thus
playing an important role in disease susceptibility.
Nutr Rev. 2013 July ; 71(7): 441–457
• what is known about transplacental and translactation
exposure of these dietary phytochemicals to the
fetus/neonate?
• whether the exposure to dietary phytochemicals during
lactation and pregnancy could modify the fetal epigenome
providing protection to the offspring?
Nutr Rev. 2013 July ; 71(7): 441–457
Dietaryphytochemicalsimpactingthreeepigenetic
codes
Nutr Rev. 2013 July ; 71(7): 441–457

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Epigeneticconsequencesof fetalprogramming
Nutr Rev. 2013 July ; 71(7): 441–457
Variousdietaryphytochemicalswith chemicalstructure
and role in general cancersand transplacentalmodels
Vegetablesand fruitfood: for acutelymphoblasticleukemia
inrelationto pre-pregnancy maternal diet
Cancer Causes & Control, Vol. 15, No. 6 (Aug., 2004), pp. 559-570
• Disruption of epigenetic mechanisms can result in oxidative
stress, obesity, insulin resistance, diabetes, and vascular
dysfunction in animals and humans.
• Despite a recognized role for epigenetics in fetal programming
of metabolic syndrome, research on therapies is still in its
infancy.
• Possible interventions include:
• 1) inhibition of DNA methylation, histone deacetylation, and
microRNA expression;
• 2) targeting epigeneticallydisturbed metabolic pathways;and
• 3) dietary supplementation with functional amino acids,
vitamins, and phytochemicals
Antioxid. Redox Signal. 2012;17, 282–301.
Nutritionalcontent of selectedplants for daily
consumptionfor pregnant women
IJPR Volume 4 Issue 4 (2014)
Numberof phytochemicalspresentin each plant
IJPR Volume 4 Issue 4 (2014)

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Pregnancynutrients
• Key nutrients in pregnancy include
• vitamin B-12, vitamin D, iron, and folate
• Key nutrients in lactation include
• vitamin B-12, vitamin D, calcium, and zinc.
Journal of the AMERICAN DIETETIC ASSOCIATION 2009;
109(7): 1271
fetalbasis of adult disease (FEBAD)
hypothesis
• In 1992, Barker and colleagues laid the groundwork for the
“fetal basis of adult disease” (FEBAD) hypothesis, postulating
that, because organs undergo developmental programming in
utero that predetermines subsequent physiologic and
metabolic adaptation during adult life, prenatal insults such as
nutritional deprivation or environmental exposures that
disturbed developmental rogramming could lead to a higher
risk of disease in adulthood.
• They showed that abdominal fatness in adult men, an indicator
of increased risk of cardiovascular disease and diabetes
independent of body mass, was associated with retarded fetal
growth, suggesting a persisting response to adverse conditions
in fetal life
Reproductive Toxicology 31 (2011) 363–373
Reproductive Toxicology 31 (2011) 363–373
• Due to the fact that flavonoids are present in a variety of food
sources, the incidental daily intake can be as high as 1 g but
can increase up to several grams in those supplementing their
diet with flavonoids.
• The average daily dietary intake of quercetin is in the range of
4–68 mg.
• Daily isoflavone intake in Western countries is approximately
1–9 mg.
• In Asian countries, however, the daily intake of isoflavones is
much higher, reaching levels of 20–240 mg, because of the
high consumption of soy (Skibola and Smith, 2000).
• It is also noteworthy that the metabolism of phytoestrogens is
different in the fetus and adults.
TOXICOLOGICAL SCIENCES 120(1), 59–67 (2011)
Ann. N.Y. Acad. Sci. 2006;1089: 14–35
Southeast Asian Journal of Tropical Medicine and Public Health; Sep
2011; 42, 5: 1214-1223

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Southeast Asian Journal of Tropical Medicine and Public Health; Sep
2011; 42, 5: 1214-1223
Biochemical Pharmacology 80 (2010) 1771–1792
Biochemical Pharmacology 80 (2010) 1771–1792 Biochemical Pharmacology 80 (2010) 1771–1792
Biochemical Pharmacology 80 (2010) 1771–1792 Biochemical Pharmacology 80 (2010) 1771–1792

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Biochemical Pharmacology 80 (2010) 1771–1792 Biochemical Pharmacology 80 (2010) 1771–1792
Biochemical Pharmacology 80 (2010) 1771–1792 Biochemical Pharmacology 80 (2010) 1771–1792
Biochemical Pharmacology 80 (2010) 1771–1792
Thank you for your attention.
Questions and Comments:
tevfik@yoldemir.com