The effect of mono-(2-ethylhexyl) phthalate on apoptosis of rat ovarian granulosa cells in vitro

Li, Na; Liu, Keqiang; Yuan, Hai-Tao; Zhu, Jian; Yu, Ge; Xie, Jingli; Fu, Songpo; Guo, Kun; Lin, Ye

doi:10.1016/j.etap.2015.01.005

Cited by 21 publications

(23 citation statements)

References 40 publications

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“…DEHP may cause many adverse effects, in addition to reproductive toxicity or embryo toxicity [11][12][13], a possible regulating mechanism in the HPTA could account for the influence of thyroid. As previously demonstrated during growth of rats, TRH is regulated by the hypothalamic system to release into the pituitary and stimulate TSH production.…”

Section: Discussionmentioning

confidence: 99%

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Correction and Republication: Effect of Di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-thyroid axis in adolescent rat

et al. 2018

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Abstract. Di-(2-ethylhexyl) phthalate (DEHP) is extensively used in many personal care and consumer products, which has resulted in widespread human exposure. Limited studies have suggested that exposure to DEHP may affect thyroid function, but little is known about the effect and mechanisms of DEHP exposure on the hypothalamic-pituitary-thyroid axis (HPTA). The present study was conducted to elucidate the potential mechanisms in which DEHP disrupts the function of the HPTA. Wistar rats were administered DEHP by gavage at 0, 5, 50, and 500 mg/kg/day for 28 days and then sacrificed within 24 h following the last dose. Hormones of HPTA was quantified with radioimmunoassay and enzyme-linked immunosorbent assay, protein levels of thyrotropin-releasing hormone receptor (TRHR) and thyroid-stimulating hormone receptor (TSHR) were analyzed by Western blot and immunohistochemistry, expression levels of TRHR and TSHR mRNA were measured by quantitative real-time PCR. Rats treated with DEHP resulted in increased bodyweight, on the HPTA, down-regulated the protein levels of TRH in the hypothalamus, up-regulated the protein and mRNA levels of TRHR in the pituitary, downregulated mRNA expression of TSHR in the thyroid, while the difference of TSH in various dose groups was not statistically significant and T3, T4, FT3, FT4 levels in serum were decreased compared with control. DEHP could interfere with the balance of HPTA of adolescent rats, and increase the body weight, down-regulate the homeostasis of thyroid related hormones and receptors expression levels. Correspondence to: Lin Ye, Department of Occupational and Environmental Health, School of Public Health, Jilin University, 1163 Xin Min Street, Changchun, 130021, China. E-mail: jlyelin@163.com *These authors equally contributed to this work. Abbreviations: DEHP, Di-(2-ethylhexyl) phthalate; EEDs, environmental endocrine disruptors; HPTA, hypothalamic-pituitary-thyroid axis; MEHP, mono-(2-ethylhexyl) phthalate; PAEs, Phthalic acid esters; PVC, polyvinyl chloride; QPCR, quantitative real-time PCR; THs, thyroid hormones; TRH, thyrotropin-releasing hormone; TRHR, thyrotropin-releasing hormone receptor; TSH, thyroidstimulating hormone; TSHR, thyroid-stimulating hormone receptor ambient air, water sources, and sediments [5][6][7]. Human exposure to PAEs mainly occurs through food due to the use of PVC in wrapping materials and food processing [1,8]. Once ingested through food contamination, di-(2-ethylhexyl) phthalate (DEHP), one of the most widely used and studied phthalates esters, is quickly metabolized to its monoester equivalent mono-(2-ethylhexyl) phthalate] (MEHP), which is preferentially absorbed [9,10]. The biological effects of MEHP are hence of major concern; however, gaining an understanding of the underlying mechanistic events has posed several challenges. In the past, researches about DEHP mainly focused on reproductive defects [11][12][13]. More recently, greater attention has been paid on the thyroid toxic of DEHP.The thyroid is the largest endocrine organ in h...

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Section: Discussionmentioning

confidence: 99%

“…The biological effects of MEHP are hence of major concern; however, gaining an understanding of the underlying mechanistic events has posed several challenges. In the past, researches about DEHP mainly focused on reproductive defects [11][12][13]. More recently, greater attention has been paid on the thyroid toxic of DEHP.…”

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confidence: 99%

Correction and Republication: Effect of Di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-thyroid axis in adolescent rat

et al. 2018

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“…It has been revealed that MEHP less than 25μM had no significant effect on the cell proliferation . We further checked the potential effects of nanomolar concentrations of MEHP on proliferation and migration of melanoma cells.…”

Section: Resultsmentioning

confidence: 98%

Promotion effects of mono‐2‐ethyhexyl phthalate (MEHP) on migration and invasion of human melanoma cells via activation of TGF‐β signals

Fan

Zuo

et al. 2019

Cell Biochemistry & Function

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Malignant melanoma is one of the most leading forms of skin cancer associated with a low patient survival rate. There is an urgent need to illustrate risk factors that can trigger the motility of melanoma cancer cells. Our present study revealed that mono-(2ethylhexyl)phthalate (MEHP) exposure can significantly increase the in vitro migration and invasion of WM983A and A375 cells. Among the tested cytokines, MEHP can increase the expression of transforming growth factor β (TGF-β). Inhibition of TGF-β via its neutralization antibody can attenuate MEHP-induced cell migration and invasion. Further, upregulation of TGF-β mediated MEHP-induced activation of Smad signals and upregulation of Snail in melanoma cells. Blocking the TGF-β/Smad signal pathway can attenuate MEHP-induced cell migration. Estrogen receptor α (ERα) was essential for MEHP-induced expression of TGF-β. In addition, MEHP can increase the expression of ERα in melanoma cells. Collectively, our study found that MEHP can stimulate the progression of melanoma via TGF-β signals. Significance: Mono-(2-ethylhexyl)phthalate (MEHP) is the active and most toxic metabolite of di(2-ethylhexyl)phthalate (DEHP). Our present study revealed that MEHP can trigger the in vitro migration and invasion of melanoma cells via upregulation of TGF-β/Snail signals. It revealed that daily exposure to MEHP might be a risk factor for melanoma patients.

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“…Thus, the authors suggested that phthalate metabolites may lead to decreased expression of cell-cycle regulators and antiapoptotic regulators, while leading to increased expression of proapoptotic factors; all this leading to the inhibition of follicular growth [44]. Li et al [45] studied the apoptotic effects of different concentrations of MEHP on rat ovarian granulosa cells in vitro. High doses of MEHP inhibited granulosa cell viability and increased apoptosis rates.…”

Section: Search Strategy and Data Extractionmentioning

confidence: 99%

Water and soil pollution as determinant of water and food quality/contamination and its impact on female fertility

Rashtian

Chavkin²,

Merhi

2019

Reprod Biol Endocrinol

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A mounting body of the literature suggests that environmental chemicals found in food and water could affect female reproduction. Many worldwide daily-used products have been shown to contain chemicals that could incur adverse reproductive outcomes in the perinatal/neonatal periods, childhood, adolescence, and even adulthood. The potential impact of Bisphenol A (BPA), Phthalates and Perfluoroalkyl substances (PFAS) on female reproduction, in particular on puberty, PCOS pathogenesis, infertility, ovarian function, endometriosis, and recurrent pregnancy loss, in both humans and animals, will be discussed in this report in order to provide greater clinician and public awareness about the potential consequences of these chemicals. The effects of these substances could interfere with hormone biosynthesis/action and could potentially be transmitted to further generations. Thus proper education about these chemicals can help individuals decide to limit exposure, ultimately alleviating the risk on future generations.

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The effect of mono-(2-ethylhexyl) phthalate on apoptosis of rat ovarian granulosa cells in vitro

Cited by 21 publications

References 40 publications

Correction and Republication: Effect of Di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-thyroid axis in adolescent rat

Correction and Republication: Effect of Di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-thyroid axis in adolescent rat

Promotion effects of mono‐2‐ethyhexyl phthalate (MEHP) on migration and invasion of human melanoma cells via activation of TGF‐β signals

Water and soil pollution as determinant of water and food quality/contamination and its impact on female fertility

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