Exposure to diethylhexyl phthalate (DEHP) results in a heritable modification of imprint genes DNA methylation in mouse oocytes

Li, Lan; Zhang, Teng; Qin, Xu‐Jie; Ge, Wei; Ma, Haifeng; Sun, Li-Lan; Hou, Zhu-Mei; Chen, Hong; Chen, Ping; Qin, Guo-Qing; Shen, Wei; Zhang, Xifeng

doi:10.1007/s11033-013-2967-7

Cited by 100 publications

(72 citation statements)

References 27 publications

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“…Hypomethylation of Tbx15 has previously been correlated with low birth weight, which is a risk factor for the development of obesity in adults (35). In the present study, DNA methylation of Tbx15 was not detected; however, a recent study has reported that gestational exposure to DEHP at 40 mg/kg may affect the DNA methylation of imprinting genes in fetal germ cells and growing oocytes, and in the offspring's oocytes (36). Therefore, it was inferred in the present study that the differential expression levels of Tbx15 mRNA in subcutaneous and visceral fat tissues between the control and DEHP groups may be due to an alteration in Tbx15 methylation status following in utero DEHP exposure.…”

Section: Dehp (Mg) --------------------------------------------------contrasting

confidence: 77%

In utero exposure to di-(2-ethylhexyl) phthalate induces metabolic disorder and increases fat accumulation in visceral depots of C57BL/6J mice offspring

Liu

Wang

et al. 2016

Experimental and Therapeutic Medicine

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Abstract.Excessive visceral fat accumulation is associated with metabolic disorders. Di-(2-ethylhexyl) phthalate (DEHP), a candidate environmental obesogen, affects lipid metabolism and adipogenesis. Perinatal exposure to DEHP may be associated with metabolic disorders of dams and offspring. The aim of the present study was to explore the effects of exposure of pregnant dams to DEHP on the metabolism and fat distribution of their offspring, and to determine the mechanisms for these effects. Pregnant C57BL/6J mice were administered DEHP via gavage (0.05 or 500 mg/kg/day) from gestational days 1-19. Pups were sacrificed at nine weeks of age. Serum leptin, insulin, lipid and fasting glucose levels, and the weights of the inguinal (subcutaneous) and gonadal (visceral) fat pads were determined. mRNA expression levels of two developmental genes, T-box 15 (Tbx15) and glypican 4 (Gpc4) were detected in fat tissues. A 100% abortion rate was exhibited in 500 mg/kg DEHP-treated dams, whereas exposure to 0.05 mg/kg DEHP did not affect reproductive outcomes. Pups from the 0.05 mg/kg exposure group were used for subsequent experimentation. Serum leptin, insulin, lipid and fasting glucose concentrations in these pups were significantly higher than those of control pups (P<0.05). Although no significant change in body weight was detected, the visceral fat weights of DEHP-exposed pups were significantly higher than those of control pups (P<0.05). Compared with controls, mRNA expression levels of Tbx15 in subcutaneous fat and Gpc4 in visceral fat were significantly increased among DEHP-exposed pups (P<0.01). The present results suggest that in utero exposure to an environmentally safe dose of DEHP may lead to excessive visceral fat accumulation and metabolic disorders in offspring and that aberrant expression of Tbx15 and Gpc4 may have an important role in these effects.

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Section: Dehp (Mg) --------------------------------------------------contrasting

confidence: 77%

In utero exposure to di-(2-ethylhexyl) phthalate induces metabolic disorder and increases fat accumulation in visceral depots of C57BL/6J mice offspring

Liu

Wang

et al. 2016

Experimental and Therapeutic Medicine

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“…14,27 It has been demonstrated that glucuronidation is one of the detoxification mechanisms in the body and that the detoxification capacity of phthalates is decreased in case of low-grade glucuronidation. Authors found that there was low-grade glucuronidation in the autism spectrum disorder group.…”

Section: Discussionmentioning

confidence: 99%

Increased Serum Phthalates (MEHP, DEHP) and Bisphenol A Concentrations in Children With Autism Spectrum Disorder

et al. 2015

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The aim of this study was to investigate the relationship between autism spectrum disorders development and exposure to mono-(2-ethylhexyl)-phthalate (MEHP), di-(2-ethylhexyl)-phthalate (DEHP), and bisphenol A (BPA), 1 of the endocrine disruptors, among phthalates. The study included 48 children with autism spectrum disorder (27 boys, 21 girls) and 41 healthy subjects (24 boys, 17 girls) as controls. Serum MEHP, DEHP, and BPA levels were measured by using high-performance liquid chromatography. Children with autism spectrum disorder had significantly increased serum MEHP, DEHP, and BPA concentrations (0.47 ± 0.14 µg/ml, 2.70 ± 0.90 µg/ml, 1.25 ± 0.30 ng/ml) compared to healthy control subjects (0.29 ± 0.05 µg/ml, 1.62 ± 0.56 µg/ml, 0.88 ± 0.18 ng/ml) respectively (P = .000). The fact that higher serum MEHP, DEHP, and BPA were found levels in the autism spectrum disorder group compared to healthy controls suggests that endocrine disruptors may have a role in the pathogenesis of autism spectrum disorders.

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“…[dibutil ftalat dibutyl phthalate (DBP)]'nin c-myc proto-onkogeninde hipometilasyona yol açarak cmyc'yi aktive ettiği bildirilmiştir. 88 90 Fetal testis DEHP'in ana hedefidir. DEHP'ye maternal maruziyetin fare testisinde DNA metilasyonunu ve DNA metiltransferaz ekspresyonunu artırdığı belirlenmiştir.…”

Section: R Re Ea Ak Kt Ti If F Ounclassified

Epigenetic Effects of Endocrine Disrupting Chemicals: Phthalates: Review

Erkekoğlu¹,

Kahvecioğlu²,

Koçer-Gümüşel³

2016

Turkiye Klinikleri J Pharm Sci

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Exposure to diethylhexyl phthalate (DEHP) results in a heritable modification of imprint genes DNA methylation in mouse oocytes

Cited by 100 publications

References 27 publications

In utero exposure to di-(2-ethylhexyl) phthalate induces metabolic disorder and increases fat accumulation in visceral depots of C57BL/6J mice offspring

In utero exposure to di-(2-ethylhexyl) phthalate induces metabolic disorder and increases fat accumulation in visceral depots of C57BL/6J mice offspring

Increased Serum Phthalates (MEHP, DEHP) and Bisphenol A Concentrations in Children With Autism Spectrum Disorder

Epigenetic Effects of Endocrine Disrupting Chemicals: Phthalates: Review

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