Di (2-ethylhexyl) phthalate exposure during pregnancy disturbs temporal sex determination regulation in mice offspring

Wang, Yongan; Liu, Wei; Yang, Qin; Yu, Mingxi; Zhang, Zhou

doi:10.1016/j.tox.2015.07.009

Cited by 21 publications

(11 citation statements)

References 63 publications

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“…Phthalates can affect the genes listed in Table 6 in male and female reproductive system tissue [ 238 , 239 ]. NRs regulate the expression of these genes [ 240 ].…”

Section: Intracellular Signaling Mechanisms Of Phthalates’ Action mentioning

confidence: 99%

“…NRs regulate the expression of these genes [ 240 ]. Altered gene expression directly influences reproductive health and hormone secretion [ 238 , 241 ].…”

Section: Intracellular Signaling Mechanisms Of Phthalates’ Action mentioning

confidence: 99%

“…Phthalates can influence their function. In the animal studies, maternal exposure to DEHP at 350, 700 mg/kg [ 238 ] and 2, 20, 200 mg/kg [ 239 ] induced the up-regulation of Wnt4, Foxl2, and Rspo1 in mice embryos, and this could lead to premature ovaries occurrence [ 238 , 239 ].…”

Section: Intracellular Signaling Mechanisms Of Phthalates’ Action mentioning

confidence: 99%

See 2 more Smart Citations

Effects and Mechanisms of Phthalates’ Action on Reproductive Processes and Reproductive Health: A Literature Review

Hlisníková

Petrovičová

Kolena

et al. 2020

IJERPH

164

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The production of plastic products, which requires phthalate plasticizers, has resulted in the problems for human health, especially that of reproductive health. Phthalate exposure can induce reproductive disorders at various regulatory levels. The aim of this review was to compile the evidence concerning the association between phthalates and reproductive diseases, phthalates-induced reproductive disorders, and their possible endocrine and intracellular mechanisms. Phthalates may induce alterations in puberty, the development of testicular dysgenesis syndrome, cancer, and fertility disorders in both males and females. At the hormonal level, phthalates can modify the release of hypothalamic, pituitary, and peripheral hormones. At the intracellular level, phthalates can interfere with nuclear receptors, membrane receptors, intracellular signaling pathways, and modulate gene expression associated with reproduction. To understand and to treat the adverse effects of phthalates on human health, it is essential to expand the current knowledge concerning their mechanism of action in the organism.

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“…Phthalates can affect the genes listed in Table 6 in male and female reproductive system tissue [ 238 , 239 ]. NRs regulate the expression of these genes [ 240 ].…”

Section: Intracellular Signaling Mechanisms Of Phthalates’ Action mentioning

confidence: 99%

“…NRs regulate the expression of these genes [ 240 ]. Altered gene expression directly influences reproductive health and hormone secretion [ 238 , 241 ].…”

Section: Intracellular Signaling Mechanisms Of Phthalates’ Action mentioning

confidence: 99%

See 1 more Smart Citation

Effects and Mechanisms of Phthalates’ Action on Reproductive Processes and Reproductive Health: A Literature Review

Hlisníková

Petrovičová

Kolena

et al. 2020

IJERPH

164

View full text Add to dashboard Cite

show abstract

“…Di‐(2‐ethylhexyl) phthalate (DEHP) is a confirmed environmental endocrine disruptor that is widely used as a plasticizer in industrial production and is encountered in daily life . Many reports have shown that DEHP can cause a variety of male reproductive abnormalities, such as cryptorchidism and hypospadias, partially through its antiandrogen effects …”

Section: Introductionmentioning

confidence: 99%

Di‐(2‐ethylhexyl) phthalate (DEHP)‐induced testicular toxicity through Nrf2‐mediated Notch1 signaling pathway in Sprague–Dawley rats

Tang

Shen

et al. 2018

Environmental Toxicology

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Di-(2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disruptor widely used in China that is harmful to the male reproductive system. Many studies have shown that DEHP causes testicular toxicity through oxidative stress, but the specific mechanism is unknown. Because the Notch pathway is a key mechanism for regulating cell growth and proliferation, we investigated whether Notch is involved in DEHP-induced testicular toxicity and whether vitamins E and C could rescue testicular impairment in Sprague-Dawley (SD) rats. Compared with the control group, we found that DEHP exposure induced testicular toxicity through oxidative stress injury, and it decreased the testosterone level (P < .01) and upregulated nuclear factor-erythroid 2 related factor (Nrf2) expression (P < .01). Therefore, because oxidative stress might be the initiating factor of DEHP-induced testicular toxicity, treatment with the antioxidant vitamins E and C activated the Notch1 signaling pathway in the testis and in Leydig cells. Treatment with vitamins E and C normalized the oxidative stress state after DEHP exposure and restored testicular development to be similar to the control group. In summary, antioxidant vitamins E and C may be used to treat DEHP-induced testicular toxicity.

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“…Our study established hypospadias rat models resulting from intrauterine exposure to DEHP, and the oxidative stress and apoptotic conditions within penis of fetal rats were detected, aiming to explore the probable mechanisms about the occurrence of hypospadias. The DEHP we utilized could easily contribute to dysplasia of male reproductive system, for instance, enabling male offsprings with enorchismus, hypospadias, degradation of sperm quality and even infertility (Skinner, ; Y. Wang, Liu, Yang, Yu, & Zhang, ). It was previously reported that abundant reactive oxygen species (ROS) were generated after entry of DEHP into the human body, which directly made for cell apoptosis (Tetz et al, ).…”

Section: Discussionmentioning

confidence: 99%

MiR‐145‐modulated SOX9‐mediated hypospadias through acting on mitogen‐activated protein kinase signaling pathway

Shang

Kang

Sun

et al. 2018

Journal Cellular Physiology

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This study primarily explored how miR‐145, mitogen‐activated protein kinase (MAPK) signaling and a downstream transcription factor (i.e., SOX9) mediated development of hypospadias. The hypospadias tissues and preputial tissues were isolated from pediatric inpatients postoperatively. Simultaneously, the rat models of hypospadias were established, and spermatogonial stem cells were separated. The expressions of proteins that symbolized cell apoptosis and oxidative stress were quantified via western blot analysis. Furthermore, the apoptosis, proliferation, and viability of cells were evaluated by means of flow cytometry, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) and colony formation assays. The results of microarray indicated miR‐145 as a differentially expressed biomarker between hypospadias tissues and normal tissues (p < 0.05). Moreover, rat models of hypospadias were observed with markedly lower vitamins A and E levels, reduced expressions of proteins relevant to oxidative stress (i.e., Nrf2, HO‐1, Gpx, and SOD‐1), as well as enhanced Bax and cleaved caspase‐3 expressions ( p < 0.05). Furthermore, SOX9 was found to be targeted by miR‐145, and it was also modified by phosphorylated extracellular‐regulated kinase (p‐ERK), a portion of MAPK signaling ( p < 0.05). The p‐ERK was significantly regulated after altering the expression of miR‐145 ( p < 0.05). Moreover, activation of p‐ERK and transfection of pcDNA‐SOX9 could cause higher expression of apoptins and larger apoptotic proportion of cells ( p < 0.05), yet transfection of miR‐145 mimic led to improved cell apoptosis and depressed cell viability ( p < 0.05). In conclusion, SOX9, which was regulated by both miR‐145 and miR‐145/MAPK signaling, could be involved in the pathogenesis of hypospadias.

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Di (2-ethylhexyl) phthalate exposure during pregnancy disturbs temporal sex determination regulation in mice offspring

Cited by 21 publications

References 63 publications

Effects and Mechanisms of Phthalates’ Action on Reproductive Processes and Reproductive Health: A Literature Review

Effects and Mechanisms of Phthalates’ Action on Reproductive Processes and Reproductive Health: A Literature Review

Di‐(2‐ethylhexyl) phthalate (DEHP)‐induced testicular toxicity through Nrf2‐mediated Notch1 signaling pathway in Sprague–Dawley rats

MiR‐145‐modulated SOX9‐mediated hypospadias through acting on mitogen‐activated protein kinase signaling pathway

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