Dipentyl phthalate induces multinucleated germ cells and reduces testosterone in the rat fetal testis with a similar dose-response
On this page:
Phthalic acid esters (phthalates) are a class of compounds that are used to plasticize polyvinyl chloride, as additives in personal care products, and in food contact products. Certain phthalates have toxic effects during fetal development, causing disruption of testosterone production, altered fetal testicular morphogenesis, and subsequent defects in male reproductive tract development and function. These effects are collectively known as phthalate syndrome. Dipentyl phthalate (DPeP) reduces testosterone with a lower effective dose than other phthalates in rat fetal testis. The aim of this study was to test whether testosterone reduction or altered cord morphogenesis is a more sensitive endpoint for DPeP toxicity in late gestation. Pregnant Sprague Dawley rats were treated with 0, 1, 11, 33, or 100 mg DPeP/kg/d by oral gavage on gestational days (GD) 17-21. Testosterone was measured using an ex vivo testosterone production bioassay, and histological sections were prepared for H&E immunofluorescent labeling of CD31 or VASA. Seminiferous cord dysgenesis was assessed by counting multinucleated germ cells (MNGs) using VASA-stained slides, and vascular development was assessed by counting vessels through CD31 staining. We found that DPeP significantly induced MNGs at 33 mg DPeP/kg/d with an estimated ED50 of 12.29 mg DPeP/kg/d, based on H&E histological sections. Testosterone, VASA+ MNG count, and CD31+ blood vessel count were not significantly altered at any dose; these experiments will be replicated with a larger sample size. Our results suggests that DPeP induces MNGs at a low dose in late gestation which represents a sensitive endpoint that can be incorporated into phthalate risk assessment.