Prenatal exposure to DEHP induces premature reproductive senescence in male mice

Radwa Barakat, Po Ching Patrick Lin, Saniya Rattan, Emily Brehm, Igor F. Canisso, Mohamed E. Abosalum, Jodi A. Flaws, Rex Hess, Che Myong Ko

Research output: Contribution to journalArticle

Abstract

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 μg/kg/day, or 750 μg/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 μg/kg/day group of mice exhibited significantly reduced fertility. At 19 months of age, 86% of the 750 μg/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.

Original languageEnglish (US)
Pages (from-to)96-108
Number of pages13
JournalToxicological Sciences
Volume156
Issue number1
DOIs
StatePublished - Mar 1 2017

Keywords

  • DEHP
  • Endocrine disruptor
  • Fertility
  • Semen
  • Testes

ASJC Scopus subject areas

  • Toxicology

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