Endocrine Disrupters and Epigenetics

• Published in: Journal of clinical research in pediatric endocrinology Vol. 7; no. 2
• Main Author: Çogulu, Özgür
• Format: Journal Article
• Language: English; Turkish
• Published: Istanbul Galenos Publishing House 01.09.2015
• Subjects: Endocrine disruptors; Epigenetics
• ISSN: 1308-5727

Our world is getting more contaminated by many chemicals each day which goes parallel to the developments in technology. At 16th-17th centuries following chemical revolution, thousands of man-made chemical substances have been introduced into the daily life of human. In the last 20-30 years, increased number of reproductive and infertility problems, birth defects and cancers have been reported. On the other hand, long-term monitoring regarding wildlife populations shows a negative impact on species particularly extinction. In the early 1990's, scientists declared that some of those chemicals mimic endocrine hormones and pass through placenta and blood-brain barrier, which cause adverse effects on human health and the environment. Today, more than 80 000 man-made chemicals pose a risk for wildlife and human health. Very few of them have been screened and some of those chemicals, named as Endocrine Disrupting Compounds (EDCs), cause adverse health effects, in other words toxicity, in an intact organism via endocrine system. The definition of EDC in "The State of Science of Endocrine Disrupting Chemicals-2012 Report" is as follows: "An exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny or (sub) populations. A potential endocrine disruptor is an exogenous substance or mixture that possesses properties that might be expected to lead to endocrine disruption in an intact organism, or its progeny or (sub) populations". Indeed, more than 1000 natural or synthetic substances, which have weak hormone-like activities, have been reported in the literature. However, it does not mean that they all cause toxicity in the body via endocrine system, that is, there should be an emerging evidence for those chemicals regarding their adverse effects on endocrine system including reproduction, thyroid function, brain function, insulin and glucose metabolism and obesity. Why should we be concerned? The reason why we should be concerned about those compounds is the increasing incidence of particular endocrine disorders in different populations in the last few decades. A significant increase in reproductive problems and endocrine cancers, decrease in fertility rates, increased rates of neurobehavioral and autoimmune disorders, loss of some species or reduced population of some animals, experimental studies in animals and cell cultures have raised the concerns about those chemicals' adverse effects on human health. It is interesting that 24% of human diseases are contributed to environmental factors. Studies have shown that their exposure particularly during fetal development and puberty plays a role in the development of reproductive diseases, obesity, diabetes, cancers, autoimmune diseases, Alzheimer disease, Parkinson disease, infections, birth defects and behavioral and learning problems. The effects of EDCs depend on the species, its age, gender and the amount of the ED, duration and the timing of exposure. The younger the individual at risk, the greater the risk of ED is. Therefore, prenatal, newborn and puberty periods are the most critical periods regarding susceptibility to those agents. Hypospadias, undescended testis, birth defects are the most prominent anomalies associated with endocrine disrupters. However, uterus and placenta strongly buffer those adverse effects in the prenatal period. Their immature nature of organs, blood-brain barrier and detoxification systems, perpetuation of physiology besides their exposure concentration are much higher compared to adults. The problems associated with those pollutants occur when children grow up and become adult. EDCs may be exposed by ingestion, skin contamination, inhalation, or ocular routes. The mechanism by which EDCs exert their phenotypic effect is not clear; however, studies have shown that they may have direct or indirect effects on human health. In direct way, physiological processes within cells, tissues and organs are affected via changing the production or metabolism of hormones in endocrine glands or coping or counteracting the action of hormones at target tissues. Alternatively, in indirect way, they cause changes on genome or epigenome, which result in alterations in gene expression. On the other hand, there is an emerging evidence in the literature in which epigenome is particularly involved. Epigenome is derived from epigenetics. Epigenetics refers to alterations in gene function without any change in DNA sequence that regulates the genome. In other words, it affects biological processes at the level of chromatin structure and organization. DNA methylation, histone modifications and noncoding RNA molecules are 3 main epigenetic mechanisms. It is well known that many of epigenetic marks are erased and reprogrammed during the embryonic and fetal development. They show their effects immediately by effecting the development and function, or by the prolonged accumulation of changes that altogether modify individual phenotype. However, sometimes, the information is transmitted from one generation to the next and affects the traits of offspring, which is called transgenerational epigenetics. In this situation, physiologic phenotype or disease which present in F1 generation transmits to subsequent generations through the germ-line although the subsequent generation is not directly exposed to the environmental factor or toxicant. EDs could be natural or synthetic. Natural EDs are phytoestrogens and fungal estrogens. Synthetics are hormones, pesticides, industrial agents, drugs and organic pollutants. The most common EDCs are estrogens, anti-estrogens, anti-androgens, progesterone, thyrotoxic agents, metals, aryl hydrocarbon receptor agonists and retinoids. They can be classified as polychlorinated biphenyls and organochlorine pesticides, pesticides, (organophosphates, carbamates, pyrethroids), plasticers (phthalates), bisphenol A, parabens, organic solvents, phytoestrogens, diethylstilbestrol, detergents and brominated flame-retardants. The main sources of those chemicals are food chain, contaminated household dust, insecticides, cosmetics, as well as industrial and occupational agents. The examples for those sources are polycarbonate plastics, including beverage and food storage containers, epoxy resins in the interior of metal cans, the ink used for thermal paper receipts, textiles which contain contaminants, such as flame-retardants, including tetrabromobisphenol A and polybrominated diphenyl ethers, medical (diethylstilbestrol), dental (diglycidyl methacrylate) or dietary (phytoestrogens) interventions and synthetic estrogens from anticonceptional pills, such as ethynilestradiol. In conclusion, all those chemicals should be screened for their adverse effects for human and wildlife. The studies, screening programs and standard approach for EDs should include toxicogenomics, which encompasses genomics, proteomics, metabolomics, neurotoxicology and neuroinformatics and insilico studies. This needs collaborations between countries, development of better screening approaches, improved methods of risk assessment and naturally reducing the exposures to well-known EDC.