Peroxisome proliferator activated receptor gamma in human placenta may mediate the adverse effects of phthalates exposure in pregnancy

Huang, Yujing; García, José Manuel Pérez; Shu, Weiqun; Rong, Honghui; Zhang, Lin; Wang, Yanzhou; Tan, Yao; Lin, Hui; Zeng, Hui; Chen, Jian

doi:10.1016/j.reprotox.2017.10.001

Cited by 16 publications

(5 citation statements)

References 35 publications

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“…First, phthalate diesters in this study were measured in cord blood, but the recommended approach for assessing phthalate exposure is to measure their metabolites in urine because (i) the diesters have been shown to be non-persistent in humans; they are oxidized quickly and the monoesters are excreted in urine, and (ii) parent phthalate compound contamination is difficult to avoid in the laboratory setting, and may overshadow any parent compounds in blood [ 110 ]. A similar limitation was also present in a recent study of 207 women from Southwest China, reporting associations of higher cord blood concentrations of DiBP, DBP, and DEHP with higher placental (sampled near the cord) PPARG protein at delivery, higher DEHP with higher cord blood estradiol, and higher DBP and DEHP with lower cord blood estriol [ 111 ]. More importantly for assessing sex-specific outcomes, unlike the studies by LaRocca et al , modification by fetal sex (interaction between exposure and fetal sex) was not assessed prior to testing associations stratified by sex.…”

Section: Sex-specific Placental Outcomesmentioning

confidence: 75%

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

Strakovsky

Schantz

2018

Environmental Epigenetics

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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.

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Section: Sex-specific Placental Outcomesmentioning

confidence: 75%

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

Strakovsky

Schantz

2018

Environmental Epigenetics

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“…One of the proposed modes of action of DEHP during pregnancy that contributes to adverse health effects is through activation of the peroxisome proliferator activated receptor (PPAR) gamma (γ) signaling pathway [64]. This is a potential pathway through which prenatal exposure to DEHP may affect children's immune system development.…”

Section: Discussionmentioning

confidence: 99%

Sex-Specific Associations between Prenatal Exposure to Di(2-ethylhexyl) Phthalate, Epigenetic Age Acceleration, and Susceptibility to Early Childhood Upper Respiratory Infections

Merrill,

Letourneau,

Giesbrecht

et al. 2024

Epigenomes

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Di(2-ethylhexyl) phthalate (DEHP) is a common plasticizer that can affect immune system development and susceptibility to infection. Aging processes (measured as epigenetic age acceleration (EAA)) may mediate the immune-related effects of prenatal exposure to DEHP. This study’s objective was to examine associations between prenatal DEHP exposure, EAA at three months of age, and the number of upper respiratory infections (URIs) from 12 to 18 months of age using a sample of 69 maternal–child pairs from a Canadian pregnancy cohort. Blood DNA methylation data were generated using the Infinium HumanMethylation450 BeadChip; EAA was estimated using Horvath’s pan-tissue clock. Robust regressions examined overall and sex-specific associations. Higher prenatal DEHP exposure (B = 6.52, 95% CI = 1.22, 11.81) and increased EAA (B = 2.98, 95% CI = 1.64, 4.32) independently predicted more URIs. In sex-specific analyses, some similar effects were noted for boys, and EAA mediated the association between prenatal DEHP exposure and URIs. In girls, higher prenatal DEHP exposure was associated with decreased EAA, and no mediation was noted. Higher prenatal DEHP exposure may be associated with increased susceptibility to early childhood URIs, particularly in boys, and aging biomarkers such as EAA may be a biological mechanism. Larger cohort studies examining the potential developmental immunotoxicity of phthalates are needed.

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“…However, some of these chemicals remain in the body without metabolizing and accumulate over time; phthalates can diffuse into the lipid bilayer of cells and spread to neighboring tissues because of their lipophilic structure (23). In-utero, chronic, or acute exposure results in impaired oxidative stress metabolism in the liver associated with the impaired endocrine system, cardiovascular diseases, obesity, infertility, and diabetes, according to the literature (11)(12)(13). Thus, we investigated the impact of in-utero exposure to the DHP and DCHP on the oxidative stress-induced histopathological changes in the liver as the critical metabolic organ for energy and detoxification metabolisms first time in the literature (22).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, in-utero exposure to phthalates has adverse health effects in adulthood, including diabetes, metabolic disorders, obesity, cancer, and cardiovascular diseases. On the other hand, there is no information about the biochemical and histopathologic effects of prenatal phthalate exposure in adulthood associated with liver metabolism (11).…”

Section: Introductionmentioning

confidence: 99%

Effects of the in-utero dicyclohexyl phthalate and di-n-hexyl phthalate administration on the oxidative stress-induced histopathological changes in the rat liver tissue correlated with serum biochemistry and hematological parameters

Aydemir,

Aydogan-Ahbab,

Barlas

et al. 2023

Front. Endocrinol.

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Phthalates are widely used as plasticizers in the industry and are found in cosmetics, food and drink packaging, drugs, toys, households, medical devices, pesticides, personal care products, and paints. Phthalates exert endocrine disrupting and peroxisome proliferator effects in humans and wildlife associated with the pathogenesis of various diseases, including diabetes, obesity, infertility, cardiovascular diseases, metabolic syndrome, and cancer. Since phthalates are metabolized in the liver, which regulates the body’s energy metabolism, long or short-term exposure to the phthalates is associated with impaired glucose, lipid, and oxidative stress metabolisms contributing to liver toxicity. However, the impact of in-utero exposure to DHP and DCHP on liver metabolism has not been studied previously. Thus, in this study, we evaluated serum biochemistry parameters, hematological markers, histopathological changes, and oxidative and pentose phosphate pathway (PPP) metabolisms in the liver following in-utero DHP and DCHP administration, respectively, in male and female rats. We found increased relative and absolute liver weights and impaired triglyceride, alanine transaminase (ALT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) levels upon dicyclohexyl phthalate (DCHP) and di-n-hexyl phthalate (DHP). Histopathological changes, including congestion, sinusoidal dilatation, inflammatory cell infiltration, cells with a pyknotic nucleus, lysis of hepatocytes, and degeneration of hepatic parenchyma have been observed in the liver samples of DHP and DCHP dose groups. Moreover, increased glutathione s-transferase (GST), glucose 6-phosphate dehydrogenase (G6PD), and glutathione reductase (GR) activities have been found in the liver samples of DHP and DCHP-treated rats associated with impaired pentose phosphate pathway (PPP) and oxidative stress metabolism. First time in the literature, we showed that in-utero exposure to DHP and DCHP causes liver damage associated with impaired oxidative stress metabolism in male and female rats. Our data may guide researchers and governments to regulate and restrict phthalates in industrial products.

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Peroxisome proliferator activated receptor gamma in human placenta may mediate the adverse effects of phthalates exposure in pregnancy

Cited by 16 publications

References 35 publications

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

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

Sex-Specific Associations between Prenatal Exposure to Di(2-ethylhexyl) Phthalate, Epigenetic Age Acceleration, and Susceptibility to Early Childhood Upper Respiratory Infections

Effects of the in-utero dicyclohexyl phthalate and di-n-hexyl phthalate administration on the oxidative stress-induced histopathological changes in the rat liver tissue correlated with serum biochemistry and hematological parameters

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