Di(2-ethylhexyl) phthalate exposure during prenatal development causes adverse transgenerational effects on female fertility in mice

Saniya Rattan, Emily Brehm, Liying Gao, Jodi A. Flaws

Research output: Contribution to journalArticlepeer-review

Abstract

Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant and endocrine disrupting chemical, but little is known about its effects on female reproduction. Thus, we tested the hypothesis that prenatal exposure to DEHP accelerates the onset of puberty, disrupts estrous cyclicity, disrupts birth outcomes, and reduces fertility in the F1, F2, and F3 generations of female mice. Pregnant CD-1 mice were orally dosed with corn oil (vehicle control) or DEHP (20 and 200 μg/kg/day and 500 and 750 mg/kg/day) from gestation day 10.5 until birth. F1 females were mated with untreated males to obtain the F2 generation. F2 females were mated with untreated males to produce the F3 generation. In all generations, the onset of puberty, estrous cyclicity, select birth outcomes, and fertility-related indices were evaluated. In the F1 generation, prenatal DEHP exposure (200 μg/kg/day) accelerated the onset of puberty, it (200 μg and 500 mg/kg/day) disrupted estrous cyclicity, and it (20 and 200 μg/kg/day) decreased fertility-related indices. In the F2 generation, ancestral DEHP exposure (500 mg/kg/day) accelerated the onset of puberty, it (20 and 200 μg/kg/day) disrupted estrous cyclicity, it (20 μg and 500 mg/kg/day) increased litter size, and it (500 mg/kg/day) decreased fertility-related indices. In the F3 generation, ancestral DEHP exposure (20, 200 μg, and 500 mg/kg/day) accelerated the onset of puberty, it (20 μg/kg/day) disrupted estrous cyclicity, and it (750 mg/kg/day) decreased female pup anogenital index. Collectively, these data indicate that prenatal DEHP exposure causes female reproductive problems in a multigenerational and transgenerational manner.

Original languageEnglish (US)
Pages (from-to)420-429
Number of pages10
JournalToxicological Sciences
Volume163
Issue number2
DOIs
StatePublished - Jun 1 2018

Keywords

  • DEHP
  • Fertility
  • Prenatal
  • Transgenerational

ASJC Scopus subject areas

  • Toxicology

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