Phthalate esters affect maturation and function of primate testis tissue ectopically grafted in mice

Rodriguez‐Sosa, Jose R.; Bondareva, Alla; Tang, Lin; Avelar, Gleide Fernandes de; Coyle, Krysta M.; Modelski, Mark; Alpaugh, Whitney; Conley, Alan J; Wynne‐Edwards, Katherine E.; França, Luiz R.; Meyers, Stuart A.; Dobrinski, Ina

doi:10.1016/j.mce.2014.10.004

Cited by 30 publications

(20 citation statements)

References 89 publications

(121 reference statements)

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“…Di(n-butyl) phthalate (DBP) is one of the most commonly used phthalates (Rodrigeuez-Sosa et al, 2014). Sertoli cells appear to be a primary target of the toxic effect of these chemical phthalates in rats (Richburg and Boekelheide, 1996;Kleymenova et al, 2005;Boekelheide et al, 2009) .…”

Section: Introductionmentioning

confidence: 99%

Retraction: Quantitative morphometric analysis of vimentin filaments in Sertoli cells of rats after <i>in utero</i> DBP exposure

Kume

Okayama

Sugiyama

et al. 2017

Fundam. Toxicol. Sci.

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-The intermediate filament of mature Sertoli cells is vimentin (Vim).One of the toxicological consequences of phthalate exposure is a selective decrease in Vim, an intermediate-sized (10 nm) cytoplasmic microfilament, in Sertoli cells. Vim in Sertoli cells of rats exposed in utero to 100 mg/kg/ day di(n-butyl) phthalate (DBP) on gestation days 12-21 was quantified. Immunohistochemical analysis revealed that Vim aggregated in Sertoli cells, but desmin filaments did not. Vim images were extracted from electron microscopic images using the computer program Imaris (Bitplane Scientific, Zeiss) and analyzed using Image-Pro plus (Media Cybernetics, USA). The amount of perinuclear Vim located within 0.5 μm of the nuclear membrane, where most Vim is aggregated, and the Vim volume ratios of the DBP group were similar to those of the vehicle group at 7 and 9 weeks, but those of the DBP group had decreased 0.63-times at 14 weeks and 0.48-times at 17 weeks compared to those of the vehicle groups. The present study showed that the testicular toxicity of in utero exposure to DBP seemed to be delayed type toxicity, and showed that improved morphometric methods cold be used widely for quantitative analysis of cellular cytoplasmic filaments.

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Section: Introductionmentioning

confidence: 99%

Retraction: Quantitative morphometric analysis of vimentin filaments in Sertoli cells of rats after <i>in utero</i> DBP exposure

Kume

Okayama

Sugiyama

et al. 2017

Fundam. Toxicol. Sci.

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“…The results were consistent for the responses of TM4 cells to 1x10 -3 and 2.5x10 -4 mmol/l MEHP. In the study by Nardelli et al (32), 13 DEGs associated with PPAR and cholesterol biosynthesis signaling pathways were identified using a gene expression microarray. The present study provides evidence supporting the roles of genes associated with 'focal adhesion', 'regulation of actin cytoskeleton' and 'ECM-receptor interaction' as the key functional genes that mediate the effects of low-dose MEHP in Sertoli cells.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have indicated that phthalates decrease the number of Sertoli cells per tubule in testis cross-sections in a dose dependent manner, promote disruption of cellular tight junction proteins (12), and decrease androgen receptor (13) and follicle-stimulating hormone (FSH) receptor expression. Sertoli cells appear to be the primary target of DEHP and mono-(2-ethylhexyl) phthalate (MEHP), an active metabolite of DEHP, in rodents (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Transcriptome profiling and pathway analysis of the effects of mono‑(2‑ethylhexyl) phthalate in mouse Sertoli cells

Wang

Dou

et al. 2019

Exp Ther Med

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Phthalates are confirmed to have toxic effects on the reproductive system and are likely to have further damaging actions in humans. The present study explored the molecular mechanisms of the toxic effect of mono-(2-ethylhexyl) phthalate (MEHP) on mouse Sertoli cells. Cell apoptosis and proliferation assays were used to assess the effects of MEHP on the TM4 Sertoli cell line derived from mouse testes. TM4 cells were treated with two doses of MEHP or left untreated as a control group, followed by RNA extraction and analysis using high-throughput transcriptome sequencing technology. The gene expression profile obtained was then subjected to a bioinformatics analysis to explore the molecular mechanisms of reproductive toxicity. The results revealed that 528 and 269 genes were upregulated in the high-and low-dose MEHP groups of cells compared with the control group, while 148 and 173 genes were downregulated. Gene ontology (GO) analysis indicated that the differently expressed genes were associated with the GO term 'extracellular region' of the cellular component domain in the high and low MEHP groups. Compared with the control group, eight common pathway changes were identified in the high-and low-dose MEHP groups, including 'terpenoid backbone biosynthesis'. Reverse transcription-quantitative polymerase chain reaction analysis was used to validation, and hermetic effects were observed for certain genes. These results provide an important basis and experimental data for further research into the mechanisms of phthalate-induced toxicity.

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“…For example, 10–15 nM BPA affects fetal lung development [44], and affects mammary development [45]. DEHP at 25 μM affects monkey Sertoli cell development [46]. TBT (100 nM) negatively affects human embryonal carcinoma cell gene expression and mitochondria [47, 48].…”

Section: Methodsmentioning

confidence: 99%

Effects of long-term endocrine disrupting compound exposure on Macaca mulatta embryonic stem cells

Midic

Vincent

VandeVoort

et al. 2016

Reproductive Toxicology

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Endocrine disrupting chemicals (EDCs) exert significant effects on health and physiology, many traceable to effects on stem cell programming underlying development. Understanding risk of low-level, chronic EDC exposure will be enhanced by knowledge of effects on stem cells. We exposed rhesus monkey embryonic stem cells to low levels of five EDCs [bisphenol A (BPA), atrazine (ATR), tributyltin (TBT), perfluorooctanoic acid (PFOA), and di-(2-ethylhexyl) phthalate (DEHP)] for 28 days, and evaluated effects on gene expression by RNAseq transcriptome profiling. We observed little effect of BPA, and small numbers of affected genes (≤119) with other EDCs. There was substantial overlap in effects across two, three, or four treatments. Ingenuity Pathway analysis indicated suppression of cell survival genes and genes downstream of several stress response mediators, activation of cell death genes, and modulations in several genes regulating pluripotency, differentiation, and germ layer development. Potential adverse effects of these changes on development are discussed.

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Phthalate esters affect maturation and function of primate testis tissue ectopically grafted in mice

Cited by 30 publications

References 89 publications

Retraction: Quantitative morphometric analysis of vimentin filaments in Sertoli cells of rats after <i>in utero</i> DBP exposure

Retraction: Quantitative morphometric analysis of vimentin filaments in Sertoli cells of rats after <i>in utero</i> DBP exposure

Transcriptome profiling and pathway analysis of the effects of mono‑(2‑ethylhexyl) phthalate in mouse Sertoli cells

Effects of long-term endocrine disrupting compound exposure on Macaca mulatta embryonic stem cells

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