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 μg/kg/day, 200 μg/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 to 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.
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