Last month, in Part I of this article, I reviewed the different types of epigenetic modifications and how they can adversely affect children’s health. In the current article, I discuss these modifications in more detail, including how they can be effectively prevented or reversed.
A variety of factors can lead to such epigenetic modifications, starting in the prenatal period and extending beyond and throughout an offspring’s life.
One critical lifestyle factor is chronic mental stress. Maternal psychosocial stress during pregnancy leads to epigenetic modifications that can impair fetal brain development and lead to emotional problems and mental disorders throughout an offspring’s lifetime and even over generations.1,2 According to human epidemiological and animal studies, maternal stress while the offspring is in the womb, or early-life stress suffered by the child, may increase the risk of neurological and psychiatric disorders through epigenetic modifications.2 Research indicates that epigenetic modifications are a critical means by which stressors interact with the genome, resulting in alterations in DNA structure, gene expression, and function.3
Stress is known to impact all 3 epigenetic mechanisms: miRNA expression, DNA methylation, and histone modifications.2 Exposure to stress during the prenatal period is linked to alterations in miRNA expression and DNA methylation in the placenta and brain, resulting in a potential increased risk of schizophrenia, attention-deficit hyperactivity disorder (ADHD), autism, and/or anxiety later in life.2 Furthermore, experiencing stress as a child can contribute to the etiology of depression, and the association between childhood stress and depression may be mediated by epigenetics.3
Lack of Exercise
Higher plasma glucose levels in obese mothers during pregnancy, even at concentrations lower than what would constitute gestational diabetes mellitus, are linked to adverse outcomes in the offspring.4 Alterations in DNA methylation in the fetus are thought to be responsible for the negative effects.4 However, when the mother eats a low-glycemic diet and engages in physical activity during pregnancy, these alterations in DNA methylation are reduced.4
Rodent research also indicates that exercise can suppress the negative epigenetic effects of a high-fat diet.5 Male mice that ate a high-fat diet but also exercised experienced beneficial effects on sperm miRNA and histone methylation.5 Furthermore, compared to the sedentary male rodents that were fed a high-fat diet, male offspring of rodent fathers that ate a high-fat diet and also exercised developed less type 2 diabetes mellitus and had better insulin signaling in skeletal muscle.5
Cell phones and other wireless devices are known to cause problems with childhood development via epigenetic mechanisms.6 These types of devices generate electromagnetic fields (EMFs). There are 2 types of EMFs that nearly everyone is exposed to in today’s world: 1) extremely-low-frequency EMFs originating from electronic appliances and power lines; and 2) radiofrequency radiation (RFR) from wireless devices and other routes of exposure, such as cell phones, wireless tablets, cordless phones, and cell towers. Children are exposed in utero when parents use wireless devices. After birth, children are exposed to EMFs through electronic baby monitors, wireless routers in the home, and the parents’ use of EMF-emitting devices. In the school years, EMF exposure occurs on account of increasing use of wireless educational devices in school programs, as well as increasing use of cell phones by kids.
An abundance of evidence in humans and animals indicates that long-term exposure to EMFs can adversely affect neurological development, memory, learning, attention, concentration, behavior problems, and/or sleep quality in the fetus, infant, young child, and adolescent.7-10 Maternal use of cell phones during pregnancy is linked to more behavioral problems in their children by school age compared with children whose mothers did not use cell phones during pregnancy.8,9 Specifically, in offspring of mothers who used cell phones during pregnancy, there were 25% more emotional problems, 35% more hyperactivity, 49% more conduct problems, and 34% more problems with peers.8,9
Exposure to EMF or RFR radiation does not have to trigger direct damage to DNA to cause problems.11,12 Rather, the epigenetic changes resulting from such exposures play a role in how well DNA carries out its functions, such as mitochondrial metabolism and production of proteins and immune cells.11,12
A child’s exposure to environmental toxins begins in the womb. More than 200 chemicals have been detected in a newborn’s umbilical cord blood.13 Pregnant women are exposed to numerous environmental toxins through the air, food, water, and skin.14 Cleaning and personal care products, building materials and home furnishings, electronics, food packaging, pharmaceuticals, pesticides, and herbicides are some of the sources of toxic exposure.15 Many chemicals can pass from mother to child across the placenta and through breast milk.15 Furthermore, young children are especially vulnerable to toxin exposure, since they crawl around the floor and tend to put their hands and toys into their mouths. Exposure to these toxins can lead to epigenetic changes in the fetus, infants, young children, and adolescents.16
Many chemicals are endocrine disrupters that can block the action of endogenous hormones involved in biological alterations during pregnancy. These chemicals are part of the pregnancy exposome – the external and internal exposures that occur during pregnancy – and can significantly modify maternal and perinatal health outcomes.17 Exposure to various toxins can lead to fetal loss, intrauterine growth restriction, preterm birth, birth defects, respiratory-related and other childhood diseases, neuropsychological dysfunction, early or late sexual maturation, and certain adult cancers associated with fetal or childhood toxin exposure.18 Even at low levels of exposure that would have no effect on an adult, synthetic chemicals may play a role in the development of neurodevelopmental disabilities such as autism, ADHD, dyslexia, and other cognitive dysfunction.19
Phenols, including parabens and bisphenol A (BPA), are used in the lining of food cans, plastic bottles and other plastic products, as well as in dental sealants. Triclosan is another phenol used as an antimicrobial in hand sanitizers and soaps. Researchers have observed earlier puberty in girls exposed to parabens or triclosan.20 Additionally, in animal and human epidemiological studies, exposure to BPA early in life is correlated with impaired neurodevelopment, endocrine dysfunction, childhood asthma, and possibly cardiometabolic disorders.21 This is concerning given that BPA is frequently found in 80-100% of maternal urine samples during pregnancy and postpartum.15 Triclosan is also commonly found in maternal urine, serum, and breast milk.15 Additionally, nearly 100% of maternal urine and breast milk samples contain methyl and propyl parabens.15
Phthalates are used as softeners in vinyl plastics, as solvents in many personal care products (such as lotions, shampoos, and conditioners), and as coatings in medications, among other uses. In pregnant women, higher levels of phthalates are associated with younger age, a high-fat diet, and using more cleaning and personal care products.15 Exposure to phthalates during pregnancy increases risk of preterm birth,22 and phthalate exposure in early life is linked to a greater risk of allergic diseases, altered neurodevelopment, and endocrine disruption.23 Phthalate metabolites are found in 90-100% of maternal urine samples during pregnancy and immediately after birth.15 Furthermore, phthalates or phthalate metabolites are known to cross the placental membrane.15
Herbicides & Pesticides
Glyphosate is the main ingredient in the most commonly used herbicide product. Many non-organic crops have been genetically modified to be resistant to glyphosate, so that the chemical can be sprayed liberally around the crops to kill weeds. There is concern that glyphosate can have detrimental effects on the endocrine system, reproduction, and development, and that it may be associated with cancer.24 These damaging effects may be due to epigenetic modifications.24 Glyphosate has altered global DNA methylation, histone modification, methylation of specific genes, and differential expression of non-coding RNAs in human cells and rodents.24 There is the very real possibility that this new glyphosate-induced epigenome could be heritable and could result in disease long after the exposure has ended.24
In mouse studies, adverse effects of glyphosate on female and male reproductive systems have been reported at both low doses and doses commonly found in the environment.24 Effects seen in these rodent studies include interference with the hypothalamic-pituitary-axis,25 uterine and ovarian dysfunction,26 the loss of pre- and post-implantation embryos,26 and testicular lesions.27 In-vitro studies have also observed changes in sperm motility and reduced mitochondrial function in human sperm cells.28,29
A number of pesticides also have been found to have toxic reproductive effects that are mediated by epigenetic mechanisms. Methoxychlor triggered alterations in DNA methylation in rat ovaries30 and sperm.31 Dichlorodiphenyltrichloroethane (DDT) altered DNA methylation in the rat hypothalamus.32 Atrazine (ATZ) interfered with histone modification in mouse sperm33 and miRNA levels in the rat brain and blood.34
Formula fed to infants is often reconstituted with fluoridated water, which can result in excessive fluoride intake. Fluoridation (mandated in many water districts/municipalities) represents the use of a drug for the masses without individual dosing and risk analysis. Halides, fluoride, bromide, and iodine are competitive, such that excesses of one can impact bioavailability of others. The fact that fluoride competes with iodine is particularly troubling, as iodine is necessary for the development of childhood intelligence.35 We must balance proposed dental benefits of fluoride with its potential adverse impact on health. When we tell our patients to stay well hydrated and drink lots of water, are we inadvertently causing them and their kids harm?
In a study of mother-child dyads, exposure to higher concentrations of fluoride in tap water correlated with lower non-verbal intellectual abilities, and the effect was stronger among children fed with formula.36 In another study, maternal exposure to higher concentrations of fluoride while pregnant was linked with lower IQ scores in their offspring at 3 to 4 years.37 Fluoride is one of a number of neurotoxicants present in the environment and one to which many children are regularly exposed.19 Epigenetic modifications are thought to be involved in fluoride-induced neurotoxicity.38 The means by which fluoride can cause skeletal fluorosis is also linked to epigenetic alterations in the form of DNA hypermethylation.39
There exists in our environment a toxic soup of other chemicals to which children and pregnant women are exposed. Flame retardants, perfluorinated chemicals (which are used to make consumer products water- and stain-resistant), and polychlorinated biphenyls (PCBs) are just some of the other chemicals that can have negative impacts on children’s health, both pre- and postnatally. For example, PCBs damage the reproductive tract, and being exposed to these chemicals at an early age is linked to thyroid hormone dysfunction, problems with child neurodevelopment, and low birth weight.15 When children or pregnant women are exposed to environmental toxins, it’s usually more than 1 chemical at a time. This can have cumulative effects that may be more damaging than exposure to 1 chemical alone.15
Our children are the coal miners’ canaries of human health. It is important to remember there is a big difference between surviving and thriving. We want our children to not only survive, but also to have optimal health throughout their lives. Research indicates that the key to thriving may very well be ensuring that our children’s epigenetic pathways are working the way they should. This begins with the parents tending to their own health both during pregnancy and prior to conception. Parents must tend to their children’s genetic legacy by avoiding or minimizing factors such as toxins, wireless exposure, chronic stress, or a sedentary lifestyle that will lead to damaging epigenetic modifications.
- DeSocio JE. Epigenetics, maternal prenatal psychosocial stress, and infant mental health. Arch Psychiatr Nurs. 2018;32(6):901-906.
- Babenko O, Kovalchuk I, Metz GA. Stress-induced perinatal and transgenerational epigenetic programming of brain development and mental health. Neurosci Biobehav Rev. 2015;48:70-91.
- Park C, Rosenblat JD, Brietzke E, et al. Stress, epigenetics and depression: A systematic review. Neurosci Biobehav Rev. 2019;102:139-152.
- Antoun E, Kitaba NT, Titcombe P, et al. Maternal dysglycaemia, changes in the infant’s epigenome modified with a diet and physical activity intervention in pregnancy: Secondary analysis of a randomised control trial. PLoS Med. 2020;17(11):e1003229.
- Claycombe-Larson KG, Bundy AN, Roemmich JN. Paternal high-fat diet and exercise regulate sperm miRNA and histone methylation to modify placental inflammation, nutrient transporter mRNA expression and fetal weight in a sex-dependent manner. J Nutr Biochem. 2020;81:108373.
- Sage C, Burgio E. Electromagnetic Fields, Pulsed Radiofrequency Radiation, and Epigenetics: How Wireless Technologies May Affect Childhood Development. Child Dev. 2018;89(1):129-136.
- Aldad TS, Gan G, Gao XB, Taylor HS. Fetal radiofrequency radiation exposure from 800-1900 mhz-rated cellular telephones affects neurodevelopment and behavior in mice. Sci Rep. 2012;2:312.
- Divan HA, Kheifets L, Obel C, Olsen J. Prenatal and postnatal exposure to cell phone use and behavioral problems in children. Epidemiology. 2008;19(4):523-529.
- Divan HA, Kheifets L, Obel C, Olsen J. Cell phone use and behavioural problems in young children. J Epidemiol Community Health. 2012;66(6):524-529.
- Carter B, Rees P, Hale L, et al. Association Between Portable Screen-Based Media Device Access or Use and Sleep Outcomes: A Systematic Review and Meta-analysis. JAMA Pediatr. 2016;170(12):1202-1208.
- Dasdag S, Akdag MZ, Erdal ME, et al. Long term and excessive use of 900 MHz radiofrequency radiation alter microRNA expression in brain. Int J Radiat Biol. 2015;91(4):306-311.
- Dasdag S, Akdag MZ, Erdal ME, et al. Effects of 2.4 GHz radiofrequency radiation emitted from Wi-Fi equipment on microRNA expression in brain tissue. Int J Radiat Biol. 2015;91(7):555-561.
- Goodman S. Tests Find More Than 200 Chemicals in Newborn Umbilical Cord Blood. December 2, 2009. Available at: https://www.scientificamerican.com/article/newborn-babies-chemicals-exposure-bpa/. Accessed June 9, 2021.
- Varshavsky J, Smith A, Wang A, et al. Heightened susceptibility: A review of how pregnancy and chemical exposures influence maternal health. Reprod Toxicol. 2020;92:14-56.
- Mitro SD, Johnson T, Zota AR. Cumulative Chemical Exposures During Pregnancy and Early Development. Curr Environ Health Rep. 2015;2(4):367-378.
- Yu X, Zhao B, Su Y, et al. Association of prenatal organochlorine pesticide-dichlorodiphenyltrichloroethane exposure with fetal genome-wide DNA methylation. Life Sci. 2018;200:81-86.
- Robinson O, Vrijheid M. The Pregnancy Exposome. Curr Environ Health Rep. 2015;2(2):204-213.
- Wigle DT, Arbuckle TE, Turner MC, et al. Epidemiologic evidence of relationships between reproductive and child health outcomes and environmental chemical contaminants. J Toxicol Environ Health B Crit Rev. 2008;11(5-6):373-517.
- Grandjean P, Landrigan PJ. Neurobehavioural effects of developmental toxicity. Lancet Neurol. 2014;13(3):330-338.
- Harley KG, Berger KP, Kogut K, et al. Association of phthalates, parabens and phenols found in personal care products with pubertal timing in girls and boys. Hum Reprod. 2019;34(1):109-117.
- Rochester JR. Bisphenol A and human health: a review of the literature. Reprod Toxicol. 2013;42:132-155.
- Ferguson KK, McElrath TF, Meeker JD. Environmental phthalate exposure and preterm birth. JAMA Pediatr. 2014;168(1):61-67.
- Braun JM, Sathyanarayana S, Hauser R. Phthalate exposure and children’s health. Curr Opin Pediatr. 2013;25(2):247-254.
- Rossetti MF, Canesini G, Lorenz V, et al. Epigenetic Changes Associated With Exposure to Glyphosate-Based Herbicides in Mammals. Front Endocrinol (Lausanne). 2021;12:671991.
- Pandey A, Rudraiah M. Analysis of endocrine disruption effect of Roundup(®) in adrenal gland of male rats. Toxicol Rep. 2015;2:1075-1085.
- Ingaramo P, Alarcón R, Muñoz-de-Toro M, Luque EH. Are glyphosate and glyphosate-based herbicides endocrine disruptors that alter female fertility? Mol Cell Endocrinol. 2020;518:110934.
- Owagboriaye FO, Dedeke GA, Ademolu KO, et al. Reproductive toxicity of Roundup herbicide exposure in male albino rat. Exp Toxicol Pathol. 2017;69(7):461-468.
- Anifandis G, Katsanaki K, Lagodonti G, et al. The Effect of Glyphosate on Human Sperm Motility and Sperm DNA Fragmentation. Int J Environ Res Public Health. 2018;15(6).
- Anifandis G, Amiridis G, Dafopoulos K, et al. The In Vitro Impact of the Herbicide Roundup on Human Sperm Motility and Sperm Mitochondria. Toxics. 2017;6(1).
- Zama AM, Uzumcu M. Fetal and neonatal exposure to the endocrine disruptor methoxychlor causes epigenetic alterations in adult ovarian genes. Endocrinology. 2009;150(10):4681-4691.
- Manikkam M, Haque MM, Guerrero-Bosagna C, et al. Pesticide methoxychlor promotes the epigenetic transgenerational inheritance of adult-onset disease through the female germline. PLoS One. 2014;9(7):e102091.
- Shutoh Y, Takeda M, Ohtsuka R, et al. Low dose effects of dichlorodiphenyltrichloroethane (DDT) on gene transcription and DNA methylation in the hypothalamus of young male rats: implication of hormesis-like effects. J Toxicol Sci. 2009;34(5):469-482.
- Hao C, Gely-Pernot A, Kervarrec C, et al. Exposure to the widely used herbicide atrazine results in deregulation of global tissue-specific RNA transcription in the third generation and is associated with a global decrease of histone trimethylation in mice. Nucleic Acids Res. 2016;44(20):9784-9802.
- Li B, Jiang Y, Xu Y, et al. Identification of miRNA-7 as a regulator of brain-derived neurotrophic factor/α-synuclein axis in atrazine-induced Parkinson’s disease by peripheral blood and brain microRNA profiling. Chemosphere. 2019;233:542-548.
- Levie D, Korevaar TIM, Bath SC, et al. Association of Maternal Iodine Status With Child IQ: A Meta-Analysis of Individual Participant Data. J Clin Endocrinol Metab. 2019;104(12):5957-5967.
- Till C, Green R, Flora D, et al. Fluoride exposure from infant formula and child IQ in a Canadian birth cohort. Environ Int. 2020;134:105315.
- Green R, Lanphear B, Hornung R, et al. Association Between Maternal Fluoride Exposure During Pregnancy and IQ Scores in Offspring in Canada. JAMA Pediatr. 2019;173(10):940-948.
- Dey Bhowmik A, Podder S, Mondal P, et al. Chronic exposure to environmentally relevant concentration of fluoride alters Ogg1 and Rad51 expressions in mice: Involvement of epigenetic regulation. Ecotoxicol Environ Saf. 2020;202:110962.
- Daiwile AP, Tarale P, Sivanesan S, et al. Role of fluoride induced epigenetic alterations in the development of skeletal fluorosis. Ecotoxicol Environ Saf. 2019;169:410-417.