Prenatal exposure to di-(2-ethylhexyl) phthalate and high-fat diet synergistically disrupts mouse fetal oogenesis and affects folliculogenesis

Di-(2-ethylhexyl) phthalate (DEHP) is a chemical that is widely used as a plasticizer. Plasticizers are chemicals that are added to materials to increase flexibility, durability, and strength. DEHP is abundant in products such as food storage containers, containers of personal care products, cosmetics, children’s toys, medical tubing, and blood storage bags. DEHP is known as an endocrine disrupting chemical and has the ability to leach out to the environment from products readily. Humans are exposed to DEHP through oral ingestion, inhalation, dermal contact, and during medical procedures. Exposure to DEHP alters ovarian function in humans. Additionally, foods high in fat content, regularly found in the western diet, are potential disruptors of fetal ovarian function. Due to DEHP’s high lipophilicity, high-fat foods can be easily contaminated with DEHP. Therefore, exposure to DEHP and a high-fat diet are both health concerns, especially in pregnant women, and the effects of these exposures on fetal oocyte quality and quantity should be elucidated. The goal of this study was to determine if there are synergistic effects of DEHP exposure at an environmentally relevant level (20 µg/kg body weight/day) and high-fat diet on oogenesis and folliculogenesis. To fulfill that goal, female CD-1 mice were fed with a high-fat diet (45 kcal% fat) or a control diet (10 kcal% fat) one week before mating and during pregnancy and lactation. The pregnant mice were orally dosed with DEHP (20 µg/kg body weight/day) or tocopherol-stripped corn oil (vehicle control) from E10.5 to E18.5 or until litter birth. Immunostaining was carried out to monitor meiotic gene silencing and synapsis in E18.5 oocytes, after making meiotic chromosomal spreads. At 8 days postpartum (dpp) and 21 dpp, F1 ovaries were harvested and subjected to histological evaluation. We found that treatment with an environmentally relevant dosage of DEHP and consumption of high-fat diet relevant to a western diet significantly increases synapsis defects in meiosis and affects the development of preantral follicles in the F1 generation.LimitedAuthor requested closed access (OA after 2yrs) in Vireo ETD syste