Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used phthalate, and it is an endocrine-disrupting chemical. This
study tested a hypothesis that prenatal exposure to DEHP lays the foundation for premature gonadal dysfunction and
subsequent reproductive senescence in male mice. Pregnant female CD-1 mice were orally dosed with vehicle control
(tocopherol-stripped corn oil) or with 20 lg/kg/day, 200 lg/kg/day, 500 mg/kg/day, or 750 mg/kg/day of DEHP from
gestational day 11 to birth. Overall, the prenatal DEHP exposure did not cause any overt physical health problems in male
offspring, as no significant differences in their body nor gonadal weight were seen up to the age of 23 months. However, an
age- and dose-dependent gonadal dysfunction was observed. As early as 7 months of age, the 750 mg/kg/day group of mice
exhibited significantly reduced fertility. At 19 months of age, 86% of the 750 mg/kg/day mice became infertile, whereas only
25% of the control mice were infertile. At this age, all of the DEHP-exposed mice had lower serum testosterone levels, higher
serum estradiol levels, and higher LH levels compared with control mice. Histological evaluations showed that mice
prenatally exposed to DEHP displayed a wide array of gonadal and epididymal abnormalities such as increased germ cell
apoptosis, degenerative seminiferous tubules, oligozoospermia, asthenozoospermia, and teratozoospermia in comparison
to age-matching control mice. In summary, this study shows that prenatal exposure to DEHP induces premature
reproductive senescence in male mice.