The role of epigenetics in the reproductive toxicity of environmental endocrine disruptors

Shi, Yanchao; Qi, Wen; Xu, Qi; Wang, Zheng; Cao, Xiaolian; Zhou, Liting; Lin, Ye

doi:10.1002/em.22414

Cited by 15 publications

(7 citation statements)

References 122 publications

(147 reference statements)

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“…Environmental agents can have both a positive and a negative influence on organism survival by interfering with its epigenome either by producing offspring that are resistant to a certain environmental agent or, in the latter case, by inheritance of defects caused by paternal exposure. Recent studies are focused on transgenerational effects of EDCs on epigenome and subsequent defects in upcoming progenies [ 117 ]. Most of the studies at present are animal-based studies, often using rats as a model organism.…”

Section: Resultsmentioning

confidence: 99%

Endocrine Disruptors Acting on Estrogen and Androgen Pathways Cause Reproductive Disorders through Multiple Mechanisms: A Review

Amir

Shah

Mamoulakis

et al. 2021

IJERPH

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Increasing contamination of the environment by toxic compounds such as endocrine disrupting chemicals (EDCs) is one of the major causes of reproductive defects in both sexes. Estrogen/androgen pathways are of utmost importance in gonadal development, determination of secondary sex characteristics and gametogenesis. Most of the EDCs mediate their action through respective receptors and/or downstream signaling. The purpose of this review is to highlight the mechanism by which EDCs can trigger antagonistic or agonistic response, acting through estrogen/androgen receptors causing reproductive defects that lead to infertility. In vitro, in vivo and in silico studies focusing on the impact of EDCs on estrogen/androgen pathways and related proteins published in the last decade were considered for the review. PUBMED and PUBCHEM were used for literature search. EDCs can bind to estrogen receptors (ERα and ERβ) and androgen receptors or activate alternative receptors such as G protein-coupled receptors (GPCR), GPR30, estrogen-related receptor (ERRγ) to activate estrogen signaling via downstream kinases. Bisphenol A, dichlorodiphenyltrichloroethane, dichlorodiphenyldichloroethylene, polychlorinated biphenyls and phthalates are major toxicants that interfere with the normal estrogen/androgen pathways leading to infertility in both sexes through many ways, including DNA damage in spermatozoids, altered methylation pattern, histone modifications and miRNA expression.

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Section: Resultsmentioning

confidence: 99%

Endocrine Disruptors Acting on Estrogen and Androgen Pathways Cause Reproductive Disorders through Multiple Mechanisms: A Review

Amir

Shah

Mamoulakis

et al. 2021

IJERPH

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“…The United States Environmental Protection Agency defines EED as "a substance that disrupts the synthesis, secretion, transport, binding, or attenuation of natural hormones needed to maintain homeostasis, reproduction, development, and normal behavior" (Kavlock et al, 1996). EEDs have attracted the attention of various research institutions because they may contribute to the development of endocrine system disorders in mammals and interfere with normal reproductive functions (Lucaccioni et al, 2020;Shi et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Bisphenol A Exposure Disrupts Organelle Distribution and Functions During Mouse Oocyte Maturation

Pan

Liao

et al. 2021

Front. Cell Dev. Biol.

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Bisphenol A (BPA) is one of the ubiquitous environmental endocrine disruptors (EEDs). Previous studies have shown that the reproduction toxicity of BPA could cause severe effects on the mammal oocytes and disturb the quality of mature oocytes. However, the toxic effects of BPA on the organelles of mouse oocytes have not been reported. In this study, to investigate whether BPA can be toxic to the organelles, we used different concentrations of BPA (50, 100, and 200 μM) to culture mouse oocytes in vitro. The results showed that 100 μM BPA exposure could significantly decrease the developmental capacity of oocytes. Then, we used the immunofluorescence staining, confocal microscopy, and western blotting to investigate the toxic effects of BPA on the organelles. The results revealed that mitochondrial dysfunction is manifested by abnormal distribution and decreased mitochondrial membrane potential. Moreover, the endoplasmic reticulum (ER) is abnormally distributed which is accompanied by ER stress showing increased expression of GRP78. For the Golgi apparatus, BPA-exposed dose not disorder the Golgi apparatus distribution but caused abnormal structure of Golgi apparatus, which is manifested by the decrease of GM130 protein expression. Moreover, we also found that BPA-exposed led to the damage of lysosome, which were shown by the increase of LAMP2 protein expression. Collectively, our findings demonstrated that the exposure of BPA could damage the normal function of the organelles, which may explain the reduced maturation quality of oocytes.

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“…Different patterns of change were observed at different DEHP exposure concentrations (opposite for low concentrations; consistent for the highest concentrations). The possibility of this result may be as follows: First, a single mRNA can be regulated by multiple miRNAs and other noncoding genes . The algorithm predicts that miR-2191, miR-2196, and miR-30e-3p also target PRPF3 based on the principle of base complementary pairing, and all of them may have stronger interactions with PRPF3 than miR-375.…”

Section: Discussionmentioning

confidence: 99%

“…The possibility of this result may be as follows: First, a single mRNA can be regulated by multiple miRNAs and other noncoding genes. 54 The algorithm predicts that miR-2191, miR-2196, and miR-30e-3p also target PRPF3 based on the principle of base complementary pairing, and all of them may have stronger interactions with PRPF3 than miR-375. Second, when zebrafish embryos were induced by higher concentrations of DEHP (200 μg/L and above), the expression of PRPF3 might be downregulated.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-375 Mediated Regulation on Pre-mRNA Processing Factor 3 in Zebrafish Embryos Exposed to Di-(2-ethylhexyl)phthalate at Low Concentrations

Huang

Gong

et al. 2022

Chem. Res. Toxicol.

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phthalate (DEHP) is an endocrinedisrupting chemical (EDC) that induces epigenetic alterations, apoptosis, and oxidative stress after biological exposure. MicroRNAs (miRNAs) are a class of small noncoding RNAs with many regulatory functions and play a role in organisms exposed to environmental chemicals. miRNA-mRNA prediction indicated that pre-mRNA processing factor 3 (PRPF3) is a likely target mRNA for miR-375 whose expression is altered by DEHP exposure. However, the interrelation between miR-375 and PRPF3 has not yet been confirmed experimentally. This study aimed to investigate the effects of DEHP on miR-375 and PRPF3 in zebrafish. The expression of miR-375 was downregulated, whereas PRPF3 was upregulated at both transcriptional and post-transcriptional levels upon stimulation with DEHP. The interaction between miR-375 and the 3′-untranslated region (3′-UTR) of PRPF3 was confirmed by a dual fluorescent protein assay and a dual luciferase reporter gene assay. The expression of PRPF3 at both transcriptional and post-transcriptional levels was reduced in ZF4 cells when transfected with a miR-375 mimic but increased when transfected with a miR-375 inhibitor. The results improved our understanding of molecular mechanisms of toxicity upon DEHP exposure and presented miR-375 as a potential novel toxicological biomarker for chemical exposure.

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The role of epigenetics in the reproductive toxicity of environmental endocrine disruptors

Cited by 15 publications

References 122 publications

Endocrine Disruptors Acting on Estrogen and Androgen Pathways Cause Reproductive Disorders through Multiple Mechanisms: A Review

Endocrine Disruptors Acting on Estrogen and Androgen Pathways Cause Reproductive Disorders through Multiple Mechanisms: A Review

Bisphenol A Exposure Disrupts Organelle Distribution and Functions During Mouse Oocyte Maturation

MicroRNA-375 Mediated Regulation on Pre-mRNA Processing Factor 3 in Zebrafish Embryos Exposed to Di-(2-ethylhexyl)phthalate at Low Concentrations

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