Di(2-ethylhexyl) Phthalate Alters Mouse Ovarian Follicle Numbers and Atresia In Vivo.

Di(2-ethylhexyl) phthalate (DEHP) is a common synthetic plasticizer in polyvinyl chloride products. Widespread production and use in everyday consumer, housing, and medical products represent a public health concern as humans are exposed to DEHP via ingestion, inhalation, and dermal contact. Large doses of DEHP have been shown to decrease 17β-estradiol production, prolong estrous cycles, and cause anovulation. However, the effects of DEHP on the ovary at environmentally relevant doses are unknown. Since any disturbance in folliculogenesis or ovarian follicular atresia can adversely affect reproductive function, we tested the hypothesis that in vivo treatment with DEHP disrupts folliculogenesis by altering follicle numbers and changing normal levels of atresia. To test this hypothesis, CD-1 mice (post-natal day 39) were orally dosed with tocopherol stripped corn oil (vehicle control) or DEHP (20 μg/kg/day, 200 μg/kg/day, 20 mg/kg/day, and 200 mg/kg/day; n=8/group) daily for thirty days. One ovary from each mouse was processed for histological evaluation of follicle numbers and atresia. Follicle types were counted in every tenth serial section of the ovary, and percentages of each follicle type were compared in each treatment group. Antral follicles were categorized as atretic by the presence of pyknotic bodies encompassing >10% of the follicle, and percentages of atretic follicles were compared in each treatment group. DEHP treatment significantly increased the percentage of primary follicles in the 200 μg/kg/day and 20 mg/kg/day DEHP dose groups when compared to the vehicle control group (vehicle: 17.92 ± 0.84; 200 μg/kg/day: 23.19 ± 1.37; 20 mg/kg/day: 23.36 ± 1.37; p=0.05). Additionally, DEHP significantly decreased the percentage of atretic antral follicles in the 200 μg/kg/day and 200 mg/kg/day DEHP dose groups when compared to the vehicle control group (vehicle: 56.89 ± 3.22; 200 μg/kg/day: 39.32 ± 5.92; 200 mg/kg/day: 43.11 ± 3.36; p=0.05). These data suggest that DEHP alters normal folliculogenesis by accelerating the primordial to primary follicle transition. Furthermore, these data suggest that DEHP may lead to decreased follicular atresia, perhaps as a compensatory mechanism. Supported by R01 ES019178.