Di-n-Butyl phthalate disrupts the expression of genes involved in cell cycle and apoptotic pathways in mouse ovarian antral follicles

Zelieann R. Craig, Patrick R. Hannon, Wei Wang, Ayelet Ziv-Gal, Jodi A. Flaws

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Di-n-butyl phthalate (DBP) is present in many consumer products, such as infant, beauty, and medical products. Several studies have shown that DBP causes reproductive toxicity in rodents, but no studies have evaluated its effects on ovarian follicles. Therefore, we used a follicle culture system to evaluate the effects of DBP on antral follicle growth, cell cycle and apoptosis gene expression, cell cycle staging, atresia, and 17β-estradiol (E2) production. Antral follicles were isolated from adult CD-1 mice and exposed to DBP at 1, 10, 100, and 1000 lg/ ml for 24 or 168 h. Follicles treated with vehicle or DBP at 1-100 lg/ml grew over time, but DBP at 1000 lg/ml significantly suppressed follicle growth. Regardless of effect on follicle growth, DBP-treated follicles had decreased mRNA for cyclins D2, E1, A2, and B1 and increased p21. Levels of the proapoptotic genes Bax, Bad, and Bok were not altered by DBP treatment, but DBP 1000 lg/ml increased levels of Bid and decreased levels of the antiapoptotic gene Bcl2. DBP-treated follicles contained significantly more cells in G1 phase, significantly less cells in S, and exhibited a trend for fewer cells in G2. Although DBP did not affect E2 production and atresia at 24 h, follicles treated with DBP had reduced levels of E2 at 96 h and underwent atresia at 168 h. These data suggest that DBP targets antral follicles and alters the expression of cell cycle and apoptosis factors, causes cell cycle arrest, decreases E2, and triggers atresia, depending on dose.

Original languageEnglish (US)
Article number23
JournalBiology of reproduction
Volume88
Issue number1
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Keywords

  • 17β-estradiol
  • Antral follicle
  • Apoptosis
  • Atresia
  • Cell cycle
  • Ovary
  • Phthalate
  • Toxicology

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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