Impacts of bisphenol A (BPA) and phthalate exposures on epigenetic outcomes in the human placenta

Abstract

The placenta guides fetal growth and development. Bisphenol A (BPA) and phthalates are widespread environmental contaminants and endocrine disruptors, and the placental epigenetic response to these chemicals is an area of growing research interest. Therefore, our objective was to summarize research linking BPA or phthalate exposure to placental outcomes in human pregnancies, with a particular focus on epigenetic endpoints. In PubMed, studies were selected for review (without limiting start date and ending on 1 May 2018) if they reported any direct effects of BPA or phthalates on the placenta in humans. Collectively, available studies suggest that BPA and phthalate exposures are associated with changes to placental micro-RNA expression, DNA methylation, and genomic imprinting. Furthermore, several studies suggest that fetal sex may be an important modifier of placental outcomes in response to these chemicals. Studies in humans demonstrate associations of BPA and phthalate exposure with adverse placental outcomes. Moving forward, more studies should consider sex differences (termed “placental sex”) in the measured outcomes, and should utilize appropriate statistical approaches to assess modification by fetal sex. Furthermore, more consistent sample collection and molecular outcome assessment paradigms will be indispensable for making progress in the field. These advances, together with improved non-invasive tools for measuring placental function and outcomes across pregnancy, will be critical for understanding the mechanisms driving placental epigenetic disruption in response to BPA and phthalates, and how these disruptions translate into placental and fetal health.

Oestrogenic Endocrine Disruptors in the Placenta and the Fetus

“…Furthermore, BPA can significantly induce the secretion of β-hCG, enhancing the endocrine function of the placenta, and inhibiting trophoblast invasion [52]. In addition, some findings demonstrated that exposure to BPA can alter the expression of the imprinted genes, leading to abnormal placental development, and also reduce DNA methylation in the mouse placenta to perturb fetal health via epigenetic changes [53]. Maternal exposure to BPA in early pregnancy predicts DNA methylation in newborns, which is associated with gene expression levels related to growth and metabolism.…”

Bisphenol A and Phthalates in Diet: An Emerging Link with Pregnancy Complications

“…The disrupting effect might result in long-term consequences, both in the mother and in the offspring (Figure 1). Interestingly, gender differences have consistently emerged in several studies, suggesting that similar conditions of exposure to an EDC may lead to different clinical manifestations which might be explained by several factors, such as the different expression of receptors or enzymes in EDCs target tissues and organs between male and female sexes [82].…”

“…Other mechanisms, such as the alteration of patterns of placental micro-RNA expression, DNA methylation and gene imprinting in the placenta, might be involved [82]. Interestingly, it has been observed that phthalates interfere with the expression of multiple genes, including epidermal growth factor, in the placenta at the first trimester by altering DNA methylation [78].…”

Toxicants Associated with Spontaneous Abortion in the Comparative Toxicogenomics Database (CTD)

“…Phthalatess are well known endocrine disruptors (Qureshi et al 2016). Phthalates also generate oxidative stress (Tetz et al 2013; Wang et al 2010), inflammation (Wang et al 2010) and epigenetic changes (Grindler et al 2018; Strakovsky and Schantz 2018) in gestational tissues and cells in culture, suggesting several potential mechanisms to increase risk of SA. Clarifying these mechanisms is worthy of further study.…”