Endocrine Disrupting Chemicals (EDCs) and Epigenetics

Endocrine disrupting chemicals (EDCs) are the man-made, manufactured substances that interfere with the signaling pathways of body such as hormonal system. These substances include a wide perspective of chemicals such as pesticides, pharmaceuticals and plastic softeners. Since they are daily-basis products, human and animals are constantly in the exposure zone of these chemicals, and EDCs are detectable in the body fluids.

Epigenetics is a study subject of changes in gene function which can be inherited but not observed as a change in DNA sequence.

Throughout the studies have been conducted, it has been presented that EDCs have been affecting epigenetics marks such as DNA methylation and histone modifications.

DNA methylation is the first epigenetic mark that is discovered. It simply refers to the addition of a methyl group (CH3) to the DNA itself usually to the fifth carbon of the cytosine ring. This process is important since DNA methylation is necessary for silencing retroviral elements and regulating tissue-gene expressions.

Figure 1. DNA Methylation

Histones are widely conserved protein structures that are in charge of ordering and packaging DNA.There at least eight-nine histone modification types however the well-understood ones are acetylation, phosphorylation and methylation. Histone modifications have a significant place for the organism since they act in diverse biological processes such as DNA damage and repair.

Figure 2. Histone Modification and DNA Methylation

In the scope of environment and epigenetics, the term environmental epigenetics corresponds to the environmental impacts such as industrial pollutants. Environmental epigenetic mechanism can be implemented to the organism in utero at the cellular level, for instance impairing genome which can impact the risk of disease of this organism later in life.

Recent epidemiological data indicates that the increased level of cancer cases in current developed world since 1960s may be partly because of exposure to EDCs. 

Figure 3. BPA(Biphenol A) and Phthalates

To look into cancer’s relationship with epigenetic factors, first cancer can be defined. Cancer is a genetic rooted disease that characterized with inherited or sporadic mutations that effect the mutations in the genes that deal with tissue homeostasis, control the cell cycle and/or regulate apoptosis (programmed cell death). It is also an epigenetic disease that causes mutations in chromatin-remodeling enzymes resulting in removal of DNA or histone protein marks. According to the accumulating evidence, many adult diseases including cancer have epigenetic factors.

Environmental dioxins have been named as the most toxic synthetic compounds. These substances can mimic estrogen. Its variety of effect is quite wide from immunotoxicity, dermal, hepatic toxicity and cancer. In addition to these, prototypical dioxin is a human carcinogen and cancers such as lung and hematological have been reported after dioxin exposure.

Furthermore, some studies also showed that a lot of cancer cases are due to what is called polycyclic aromatic hydrocarbons (PAH), can form when meats are grilled or barbecued. Some of these PAHs initiate cancer whereas some other triggers the mechanism for cancer to begin.

The pathways that mediate cell signaling for the endocrine disruptions induced by these chemicals however this is not limited to regulatory mechanisms (chromatin/epigenetic regulation) and cell function (development/differentiation, immune response/inflammation, apoptosis).

Figure 4. Various Effects of Pollutants on Different Mechanisms

Regarding several epidemiological studies of people living in Europe, the United States, and China have linked in utero exposure to PAHs, through air pollution or parental occupational exposure. Results are poor fetal growth, reduced immune function, and poorer neurological development.

EDCs affect male mammary gland development with transgenerational effects. Alterations have been described in male and female mammary gland morphogenesis after BPA (Bisphenol A) exposure which might contribute to breast cancer risk. Fetal exposure to the estrogen-mimetic BPA has recently been indicated to trigger epigenetic alteration in postnatal and adult rat mammary glands throughout their life and gene expression.

The health of an individual depends on the interaction of various environmental factors with the individual’s genetics. In this case, the individual’s lifestyle as a factor is likely to affect their health and their offspring through epigenetic mechanisms. Some periods of development are particularly susceptible to the harmful effects of these toxins, especially fetuses. 

Thank you for reading!

References

BIBLIOGRAPHY

[1]	C. Tiffon, "The Impact of Nutrition and Environmental Epigenetics on Human Health and Disease," International Journal of Molecular Sciences, pp. 1-19, 2018.
[2]	B. M. D. J. L. M. B. L. S. A. C. M. R. E. C. a. S. M. B. Kaley M. Major*, "Early Life Exposure to Environmentally Relevant Levels of Endocrine Disruptors Drive Multigenerational and Transgenerational Epigenetic Changes in a Fish Model," Frontiers in Marine Science, pp. 1-17, 2020.
[3]	D.-G. a. D. Rüegg, "Understanding Epigenetic Effects of Endocrine Disrupting Chemicals: from Mechanisms to Novel Test Methods," 2017.
[4]	Wikipedia, "DNA Methylation," 22 02 2022. [Online]. Available: https://en.wikipedia.org/wiki/DNA_methylation. [Accessed 2022 02 28].
[5]	S. A. S. B. Maria E.Street, "Researchgate," 06 2018. [Online]. Available: https://www.researchgate.net/figure/Importance-of-EDCs-driven-epigenetic-effects-during-life-course-and-potential_fig2_325559012. [Accessed 28 02 2022].
[6]	P. B. Barbara Predieri, "Researchgate," 04 2020. [Online]. Available: https://www.researchgate.net/figure/Relationship-suggested-between-endocrine-disrupting-chemicals-EDCs-and-type-1-diabetes_fig1_340864282. [Accessed 28 02 2022].