Altered expression of genes related to zinc homeostasis in early mouse embryos exposed to di-2-ethylhexyl phthalate

Lee, Jongwha; Park, Jong-An; Jang, Bong-Ki; Knudsen, Thomas B.

doi:10.1016/j.toxlet.2004.03.011

Cited by 18 publications

(6 citation statements)

References 37 publications

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“…It has been established that DEHP disrupts oxidative balance associated with production of a strongly oxidative damaging milieu [41], [42], increased the production of reactive oxygen species (ROS) and decreased production of protective antioxidants, as evidenced by significant decreases in glutathione peroxidase 1 (GPx1) (∼20%) and superoxide dismutase (SOD) (∼30%) activities and glutathione (GSH) levels (∼20%) in DEHP treatment (1000 mg/kg) rats [43], and might ultimately leading to carcinogenesis [44], [45]. There are several other lines of evidence relating DEHP to reproduction, such as altering the expression of several key genes in embryonic zinc homeostasis [46], inhibited equine oocyte maturation [47] and blocked mouse follicle growth through an oxidative stress pathway [48]. Partial mechanisms were also revealed by in vivo exposure of DEHP in Danio rerio , where a significant reduction of fecundity was observed.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Di-(2-ethylhexyl)-phthalate Exposure on Fertilization and Embryonic Development In Vitro and Testicular Genomic Mutation In Vivo

Huang

et al. 2012

PLoS ONE

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The present study was undertaken to determine the reproductive hazards of Di-(2-ethylhexyl)-phthalate (DEHP) on mouse spermatozoa and embryos in vitro and genomic changes in vivo. Direct low-level DEHP exposure (1 μg/ml) on spermatozoa and embryos was investigated by in vitro fertilization (IVF) process, culture of preimplanted embryos in DEHP-supplemented medium and embryo transfer to achieve full term development. Big Blue® transgenic mouse model was employed to evaluate the mutagenesis of testicular genome with in vivo exposure concentration of DEHP (500 mg/kg/day). Generally, DEHP-treated spermatozoa (1 μg/ml, 30 min) presented reduced fertilization ability (P<0.05) and the resultant embryos had decreased developmental potential compared to DMSO controls (P<0.05). Meanwhile, the transferred 2-cell stage embryos derived from treated spermatozoa also exhibited decreased birth rate than that of control (P<0.05). When fertilized oocytes or 2-cell stage embryos were recovered by in vivo fertilization (without treatment) and then exposed to DEHP, the subsequent development proceed to blastocysts was different, fertilized oocytes were significantly affected (P<0.05) whereas developmental progression of 2-cell stage embryos was similar to controls (P>0.05). Testes of the Big Blue® transgenic mice treated with DEHP for 4 weeks indicated an approximately 3-fold increase in genomic DNA mutation frequency compared with controls (P<0.05). These findings unveiled the hazardous effects of direct low-level exposure of DEHP on spermatozoa's fertilization ability as well as embryonic development, and proved that in vivo DEHP exposure posed mutagenic risks in the reproductive organ – at least in testes, are of great concern to human male reproductive health.

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Section: Discussionmentioning

confidence: 99%

The Effects of Di-(2-ethylhexyl)-phthalate Exposure on Fertilization and Embryonic Development In Vitro and Testicular Genomic Mutation In Vivo

Huang

et al. 2012

PLoS ONE

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“…This study indicates potential risks of PAE exposure. Although MTs are thought to govern the regulation of metals, this research shows that neonatal PAE exposure can alter expression of MTs 19 . The association between neonatal PAE exposure with FATP1 mRNA expression was observed in this study, which supports an effect of PAE exposure on placental essential fatty acid homeostasis.…”

Section: Discussionmentioning

confidence: 81%

“…While varied factors react to the extensive mix of PAEs, it is too complicated to specify a single-track causality. Animal studies revealed that DEHP exposure resulted in up-regulation of MT-1A and MT-2A in maternal liver, whereas both proteins were down-regulated in the embryo head 19 . Separate from their ability to directly bind metals, some metallothionein isoforms have antioxidant functions 15 , which may be the reason that MT mRNA expression is altered by exposure due to the oxidizability of PAEs.…”

Section: Discussionmentioning

confidence: 99%

Neonatal phthalate ester exposure induced placental MTs, FATP1 and HFABP mRNA expression in two districts of southeast China

Zhu

et al. 2016

Sci Rep

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Plastic production releases phthalate esters (PAEs), which can alter the expression of metallothioneins (MTs), fatty acid transport protein 1 (FATP1) and heart fatty acid binding protein (HFABP). A total of 187 mother-infant pairs were recruited, 127 from Chenghai (high exposed group) and 60 from Haojiang (low exposed group), to investigate the association between neonatal PAE exposure and mRNA expression of placental MTs, FATP1 and HFABP. Umbilical cord blood and placenta samples were collected for measuring five PAE concentrations and detecting mRNA levels of MTs, FATP1 and HFABP. Butylbenzyl phthalate (BBP), di(2-ethylhexyl) phthalate (DEHP), di-n-octyl phthalate (DNOP) were significantly higher in the high exposed group compared to the low exposed group. FATP1 and HFABP mRNA in the high exposed group were higher than that in the low exposed group while MT-1A was contrary. Both dimethyl phthalate (DMP) and DEHP were correlated with higher MT and MT-2A expression, while diethyl phthalate (DEP) was also positively correlated with MT-1A and FATP1 expression in female infants. DEHP exposure was negatively correlated with birth weight and gestational age in male infants. These results show that neonatal PAE exposure alters the mRNA expression of placental MTs and FATP1, which are related to fetal growth and development.

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“…It seems plausible to consider that cadmium may work by this mechanism except that the stress response pathway, that is, induction of metallothionein, is located in the mother and extra embryonic membranes. The concept that teratogen administration could act to limit zinc levels or activity within the embryo and thereby induce abnormal development has solid scientific support from previous studies (Daston et al, 1994; Taubeneck et al, 1994; Bui et al, 1998; Kultima et al, 2004; Lee et al, 2004; Fernåndez et al, 2007). We contribute indirect evidence in support of this general concept and suggest a novel mechanism by which lowered embryonic zinc concentration could be translated into abnormal embryogenesis, that is, posterior forelimb ectrodactyly.…”

Section: Discussionmentioning

confidence: 82%

Microarray analysis of murine limb bud ectoderm and mesoderm after exposure to cadmium or acetazolamide

Schreiner

Bell

Scott

2009

Birth Defects Research

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Altered expression of genes related to zinc homeostasis in early mouse embryos exposed to di-2-ethylhexyl phthalate

Cited by 18 publications

References 37 publications

The Effects of Di-(2-ethylhexyl)-phthalate Exposure on Fertilization and Embryonic Development In Vitro and Testicular Genomic Mutation In Vivo

The Effects of Di-(2-ethylhexyl)-phthalate Exposure on Fertilization and Embryonic Development In Vitro and Testicular Genomic Mutation In Vivo

Neonatal phthalate ester exposure induced placental MTs, FATP1 and HFABP mRNA expression in two districts of southeast China

Microarray analysis of murine limb bud ectoderm and mesoderm after exposure to cadmium or acetazolamide

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