Prenatal exposure to a mixture of phthalates accelerates the age-related decline in reproductive capacity but may not affect direct biomarkers of ovarian aging in the F1 generation of female mice

Phthalates are used in many consumer products, leading to daily human exposure. Although many studies focus on single phthalates, humans are exposed to mixtures of phthalates. Our laboratory created a phthalate mixture consisting of six different phthalates and found that it negatively affected female reproduction and accelerated some biomarkers of reproductive aging. However, it was unknown if prenatal exposure to the mixture accelerates the natural decline in reproductive capacity and ovarian aging in mice. Therefore, we tested the hypothesis that prenatal exposure to a phthalate mixture accelerates the age-related decline in reproductive capacity and biomarkers of ovarian aging in the F1 generation of mice. Pregnant CD-1 dams were orally dosed with control or phthalate mixture (20 µg/kg/day–200 mg/kg/day) daily from gestational day 10—birth. The F1 female pups were aged to 11–13 months, and then estrous cyclicity and breeding trials were conducted at 11 and 13 months. Ovaries were collected from the F1 females at 13 months to examine biomarkers of ovarian aging. Prenatal exposure to the phthalate mixture decreased the time the F1 females spent in proestrus and the ability of the F1 females to give birth at 11 and 13 months of age compared to control. In contrast, prenatal exposure to the mixture did not affect biomarkers of direct aging of the ovary in the F1 generation. Collectively, our data show that prenatal phthalate mixture exposure accelerates the natural age-related decline in reproductive capacity but may not affect some biomarkers of ovarian aging in the F1 generation.