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- W2953014037 endingPage "114629" @default.
- W2953014037 startingPage "114629" @default.
- W2953014037 abstract "Di(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer and known endocrine disrupting chemical, which causes transgenerational reproductive toxicity in female rodents. However, the mechanisms of action underlying the transgenerational toxicity of DEHP are not understood. Therefore, this study determined the effects of prenatal and ancestral DEHP exposure on various ovarian pathways in the F1, F2, and F3 generations of mice. Pregnant CD-1 dams were orally exposed to corn oil (vehicle control) or DEHP (20 μg/kg/day-750 mg/kg/day) from gestation day 10.5 until birth. At postnatal day 21 for all generations, ovaries were removed for gene expression analysis of various ovarian pathways and for 5-methyl cytosine (5-mC) quantification. In the F1 generation, prenatal DEHP exposure disrupted the expression of cell cycle regulators, the expression of peroxisome-proliferator activating receptors, and the percentage of 5-mC compared to control. In the F2 generation, exposure to DEHP decreased the expression of steroidogenic enzymes, apoptosis factors, and ten-eleven translocation compared to controls. It also dysregulated the expression of phosphoinositide 3-kinase (PI3K) factors. In the F3 generation, ancestral DEHP exposure decreased the expression of steroidogenic enzymes, PI3K factors, cell cycle regulators, apoptosis factors, Esr2, DNA methylation mediators, and the percentage of 5-mC compared to controls. Overall, the data show that prenatal and ancestral DEHP exposure greatly suppress gene expression of pathways required for folliculogenesis and steroidogenesis in the ovary in a transgenerational manner and that gene expression may be influenced by DNA methylation. These results provide insight into some of the mechanisms of DEHP-mediated toxicity in the ovary across generations." @default.
- W2953014037 created "2019-06-27" @default.
- W2953014037 creator A5022400005 @default.
- W2953014037 creator A5023106957 @default.
- W2953014037 creator A5032204838 @default.
- W2953014037 creator A5040949438 @default.
- W2953014037 creator A5045130347 @default.
- W2953014037 creator A5063631259 @default.
- W2953014037 creator A5065010929 @default.
- W2953014037 creator A5066925673 @default.
- W2953014037 date "2019-09-01" @default.
- W2953014037 modified "2023-10-16" @default.
- W2953014037 title "Prenatal and ancestral exposure to di(2-ethylhexyl) phthalate alters gene expression and DNA methylation in mouse ovaries" @default.
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