ArticleToxicology and applied pharmacology2019
Prenatal and ancestral exposure to di(2-ethylhexyl) phthalate alters gene expression and DNA methylation in mouse ovaries.
Article in Toxicology and applied pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 58 citations in OpenAlex.
- DNMT/TET Imbalance and Network-Level DNA Methylation Remodeling in Ovarian Aging: Mechanistic Perspectives.Biology · 2026Review
- Major depressive disorder and anti-depressant therapy markedly alters the human follicular niche DNA methylome.Reproduction (Cambridge, England) · 2025Article
- Perinatal Exposure to Lead or Diethylhexyl Phthalate in Mice: Sex-Specific Effects on Cardiac DNA Methylation and Gene Expression across Time.Environmental health perspectives · 2025Article
- Phthalates Impair Estrogenic Regulation of HIF2α and Extracellular Vesicle Secretion by Human Endometrial Stromal Cells.Endocrinology · 2025Article
- Environmental Health Is Overlooked in Longevity Research.Antioxidants (Basel, Switzerland) · 2025Review
- Prenatal exposure to an environmentally relevant phthalate mixture alters oxidative stress, apoptosis, cell cycle regulators, and steroidogenic factors in the ovaries of F1 mice.Reproductive toxicology (Elmsford, N.Y.) · 2025Article
- In Vitro Toxicity of a DEHP and Cadmium Mixture on Sheep Cumulus-Oocyte Complexes.International journal of molecular sciences · 2024Article
- Sperm miR-142-3p Reprogramming Mediates Paternal Pre-Pregnancy Caffeine Exposure-Induced Non-Alcoholic Steatohepatitis in Male Offspring Rats.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Prenatal exposure to an environmentally relevant phthalate mixture alters serum cytokine levels and inflammatory markers in the F1 mouse ovary.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Nutriepigenomics in Environmental-Associated Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Review
- Multi- and Transgenerational Effects of Environmental Toxicants on Mammalian Reproduction.Cells · 2022Review
- Multigenerational Effects of an Environmentally Relevant Phthalate Mixture on Reproductive Parameters and Ovarian miRNA Expression in Female Rats.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Review
- Prenatal exposure to an environmentally relevant phthalate mixture alters ovarian steroidogenesis and folliculogenesis in the F1 generation of adult female mice.Reproductive toxicology (Elmsford, N.Y.) · 2021Article
- Early postnatal exposure to di(2-ethylhexyl) phthalate causes sex-specific disruption of gonadal development in pigs.Reproductive toxicology (Elmsford, N.Y.) · 2021Article
- Multi- and Transgenerational Outcomes of an Exposure to a Mixture of Endocrine-Disrupting Chemicals (EDCs) on Puberty and Maternal Behavior in the Female Rat.Environmental health perspectives · 2021Article
- First trimester mechanisms of gestational sac placental and foetal teratogenicity: a framework for birth cohort studies.Human reproduction update · 2021Review
- The effects of plasticizers on the ovary.Current opinion in endocrine and metabolic research · 2021Article
- Ovarian Toxicity and Epigenetic Mechanisms of Phthalates and Their Metabolites.Current medical science · 2021Review
- Endocrine Disruption of the Follicle-Stimulating Hormone Receptor Signaling During the Human Antral Follicle Growth.Frontiers in endocrinology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
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.
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Registered trials
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