Prenatal Exposures of Male Rats to the Environmental Chemicals Bisphenol A and Di(2-Ethylhexyl) Phthalate Impact the Sexual Differentiation Process

Abdel-Maksoud, Fatma M.; Leasor, Khrystyna R.; Butzen, Kate; Braden, Tim D.; Akingbemi, Benson T.

doi:10.1210/en.2015-1077

Cited by 57 publications

(18 citation statements)

References 56 publications

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“…Only two previous animal studies have examined the relationship between BPA exposure and global DNA hydroxymethylation, where maternal exposure to BPA inhibited global DNA hydroxymethylation in adult rat testis and BPA exposure led to a decrease of testicular TETs and 5hmC levels in Gobiocypris rarus testes [26]. 5hmC density and function appears to vary with cell type, differentiation stage and gene specific function [38].…”

Section: Discussionmentioning

confidence: 99%

“…The enrichment of 5hmC is potentially crucial for regulation of gene expression during spermatogenesis [25]. While two recent animal studies suggested that exposure to BPA inhibited global DNA hydroxymethylation or TETs-mediated DNA demethylation [26,27], little information is available about the effect of BPA exposure on global 5hmC in humans.…”

Section: Introductionmentioning

confidence: 99%

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Association of Bisphenol A Exposure with LINE-1 Hydroxymethylation in Human Semen

Tian

Zhou

Miao

et al. 2018

IJERPH

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Bisphenol A (BPA), an exogenous endocrine-disrupting chemical, has been shown to alter DNA methylation. However, little information is available about the effect of BPA exposure on DNA hydroxymethylation in humans. The objective of the present study was to examine whether BPA exposure was associated with DNA hydroxymethylation in human semen samples. We measured urine BPA levels and LINE-1 hydroxymethylation in 158 male factory workers selected from an occupational cohort study conducted in China between 2004 and 2008. Among them, there were 72 male workers with occupational BPA exposure (BPA-exposed group) and 86 male workers without occupational BPA exposure (unexposed group). Multivariate linear regression models were used to examine the association of exposure to BPA with LINE-1 hydroxymethylation. LINE-1 was more highly hydroxymethylated in the BPA-exposed group than in the unexposed group (median 12.97% vs. 9.68%, respectively; p < 0.05), after adjusting for the potential confounders. The medians of 5-hydroxymethylcytosine (5hmC) generally increased with increasing urine BPA levels: 8.79%, 12.16%, 11.53%, and 13.45%, for undetected BPA and corresponding tertiles for the detected BPA, respectively. After analysis using data at individual level, our findings indicated that BPA exposure was associated with alterations of sperm LINE-1 hydroxymethylation, which might have implications for understanding the mechanisms underlying BPA-induced adverse effects on male reproductive function.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of Bisphenol A Exposure with LINE-1 Hydroxymethylation in Human Semen

Tian

Zhou

Miao

et al. 2018

IJERPH

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“…BPA exposure induces DNA methylation and histone protein modifications in the brain and other organs [72; 114; 115; 116; 117; 118; 119; 120; 121]. The expression of miRNAs in the placenta, liver, and likely other organs, including the brain, can also be influenced by BPA [122; 123; 124; 125].…”

Section: Overall Conclusionmentioning

confidence: 99%

Neuroendocrine disruption in animal models due to exposure to bisphenol A analogues

Rosenfeld

2017

Frontiers in Neuroendocrinology

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Animal and human studies provide evidence that exposure to the endocrine disrupting chemical (EDC), bisphenol A (BPA), can lead to neurobehavioral disorders. Consequently, there is an impetus to identify safer alternatives to BPA. Three bisphenol compounds proposed as potential safer alternatives to BPA are bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF). However, it is not clear whether these other compounds are safer in terms of inducing less endocrine disrupting effects in animals and humans who are now increasingly coming into contact with these BPA-substitutes. In the past few years, several animal studies have shown exposure to these other bisphenols induce similar neurobehavioral disruption as BPA. We will explore in this review article the current studies suggesting these other bisphenols result in neuroendocrine disruptions that may be estrogen receptor-dependent. Current work may aide in designing future studies to test further whether these BPA-substitutes can act as neuroendocrine disruptors.

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“…Altered cellular function occurring at low‐dose chemical exposures is more apt to result from receptor–ligand interactions than exposures occurring at high doses that cause cellular damage and overt toxicity. Therefore, we used a biologically based response model of low‐dose exposure paradigms of BPA at 2.5 or 25 and DEHP at 5 or 50 μg/kg bw (Abdel‐Maksoud et al ., ). Timed‐pregnant Long‐Evans dams (Harlan‐Teklad, Indianapolis, IN, USA) were grouped into four groups.…”

Section: Methodsmentioning

confidence: 97%

Exposures of male rats to environmental chemicals [bisphenol A and di (2‐ethylhexyl) phthalate] affected expression of several proteins in the developing epididymis

et al. 2017

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Hormonally active agents are released into the environment from industrial and manufacturing activity. Evidence in the literature indicates that impaired reproductive capacity in wildlife and laboratory species is associated with chemical exposures. In particular, bisphenol A (BPA) and di (2-ethylhexyl) phthalate (DEHP) have generated public interest due to their presence in several consumer products. In this study, we determined that expression of steroid hormone receptors (estrogen and androgen receptors), Wnt4, and β-catenin was greater (p < 0.05) in the rat epididymis at 35 days of age compared to 21 and 90 days. Second, timed-pregnant Long-Evans dams were exposed to the chemicals BPA and DEHP by gavage from gestational days 12-21. The caput epididymis was collected from cohorts of male offspring at 35 and 90 days of age and processed for Western blot analysis. Results showed that prenatal BPA and DEHP exposures affected (p < 0.05) expression of estrogen and androgen receptor, Wnt4, β-catenin, MAPK, and HOXD4 protein in the epididymis. Data have implications for morphological development of the epididymis, a possibility that would be explored in future studies.

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Prenatal Exposures of Male Rats to the Environmental Chemicals Bisphenol A and Di(2-Ethylhexyl) Phthalate Impact the Sexual Differentiation Process

Cited by 57 publications

References 56 publications

Association of Bisphenol A Exposure with LINE-1 Hydroxymethylation in Human Semen

Association of Bisphenol A Exposure with LINE-1 Hydroxymethylation in Human Semen

Neuroendocrine disruption in animal models due to exposure to bisphenol A analogues

Exposures of male rats to environmental chemicals [bisphenol A and di (2‐ethylhexyl) phthalate] affected expression of several proteins in the developing epididymis

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