Phthalate Exposure and Long-Term Epigenomic Consequences: A Review.

Sudipta Dutta,Daniel A Rappolee,Douglas M Ruden,Diana K Haggerty

doi:10.3389/fgene.2020.00405

Abstract

Phthalates are esters of phthalic acid which are used in cosmetics and other daily personal care products. They are also used in polyvinyl chloride (PVC) plastics to increase durability and plasticity. Phthalates are not present in plastics by covalent bonds and thus can easily leach into the environment and enter the human body by dermal absorption, ingestion, or inhalation. Several in vitro and in vivo studies suggest that phthalates can act as endocrine disruptors and cause moderate reproductive and developmental toxicities. Furthermore, phthalates can pass through the placental barrier and affect the developing fetus. Thus, phthalates have ubiquitous presence in food and environment with potential adverse health effects in humans. This review focusses on studies conducted in the field of toxicogenomics of phthalates and discusses possible transgenerational and multigenerational effects caused by phthalate exposure during any point of the life-cycle.

Highlights

Phthalates or diesters of phthalic acid are a group of ubiquitous synthetic compounds commonly found in a variety of consumer products like plasticizers since the 1930s (Koch et al, 2013)
It was demonstrated in at least two studies using human placenta that phthalate exposure during pregnancy was inversely associated with DNA methylation on selected candidate genes like H19 and insulin-like growth-factor 2 (IGF2) which are important in embryonic growth and development
This review is expected to inspire future research endeavors in environmental epigenetics to investigate the effects of the endocrine disruptors at different life stages from the perspective of transgenerational and multigenerational epigenetic inheritance (Table 1)

Summary

INTRODUCTION

Phthalates or diesters of phthalic acid are a group of ubiquitous synthetic compounds commonly found in a variety of consumer products like plasticizers since the 1930s (Koch et al, 2013). Abnormal IGF2/H19 methylation in placenta suggests the fact that the developing fetus may be exposed to an adverse intrauterine environment (LaRocca et al, 2014) It was demonstrated in at least two studies using human placenta that phthalate exposure during pregnancy was inversely associated with DNA methylation on selected candidate genes like H19 and insulin-like growth-factor 2 (IGF2) which are important in embryonic growth and development. Inverse associations were found between maternal phthalate metabolite levels and gestational age, birth weight, birth length, and BMI Taken together, these studies demonstrate that phthalate exposure in utero may impact DNA methylation in cord blood. Perhaps a more important question to answer is do we need to establish NOEALs for epigenetic research if the changes in DNA methylation are not the ultimate outcomes we seek to understand

DISCUSSION

Findings

Male reproductive stage