Ovarian metabolism of an environmentally relevant phthalate mixture

Genoa R. Warner, Zhong (Lucas) Li, Madeline L. Houde, Cassandra E. Atkinson, Daryl D. Meling, Catheryne Chiang, Jodi A Flaws

Research output: Contribution to journalArticle

Abstract

Phthalates are synthetic chemicals with widespread human exposure due to their use as additives in consumer products. Phthalate diesters are hydrolyzed in the environment and in the body to monoesters that may be more toxic than the parent compounds. This study tested the hypothesis that adult mouse antral follicles, but not neonatal ovaries, are able to metabolize an environmentally relevant mixture of phthalates. Whole neonatal ovaries and isolated adult antral follicles from CD-1 mice were cultured in media treated with vehicle control or 0.1-10 mg/ml of a mixture composed of 35% diethyl phthalate (DEP), 21% di(2-ethylhexyl) phthalate (DEHP), 15% dibutyl phthalate (DBP), 15% diisononyl phthalate (DiNP), 8% diisobutyl phthalate (DiBP), and 5% benzylbutyl phthalate (BzBP). After 4 days of culture, media were subjected to high-performance liquid chromatography tandem mass spectrometry to measure the amounts of diester phthalates and monoester metabolites. Ovaries and follicles were collected to measure the gene and protein expression of the enzymes required for phthalate metabolism. Monoester metabolites for all phthalates except DiNP were detected in the media for both culture types at most doses. The long-chain phthalates (BzBP, DEHP, and DiNP) were metabolized less than the short-chain phthalates (DEP, DBP, and DiBP) compared with respective controls. Expression of metabolizing enzymes was observed for all treatment groups in both culture types. These data indicate that mouse ovaries are capable of metabolizing low doses of phthalates and suggest that metabolic capacity differs for follicles at different stages of development.

Original languageEnglish (US)
Pages (from-to)246-259
Number of pages14
JournalToxicological Sciences
Volume169
Issue number1
DOIs
StatePublished - Jan 1 2019

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Metabolism
Dibutyl Phthalate
Ovary
Metabolites
Culture Media
phthalic acid
Consumer products
Poisons
High performance liquid chromatography
Enzymes
Mass spectrometry
Tandem Mass Spectrometry
High Pressure Liquid Chromatography
Gene Expression

Keywords

  • Follicles
  • Metabolism
  • Ovary
  • Phthalates

ASJC Scopus subject areas

  • Toxicology

Cite this

Ovarian metabolism of an environmentally relevant phthalate mixture. / Warner, Genoa R.; Li, Zhong (Lucas); Houde, Madeline L.; Atkinson, Cassandra E.; Meling, Daryl D.; Chiang, Catheryne; Flaws, Jodi A.

In: Toxicological Sciences, Vol. 169, No. 1, 01.01.2019, p. 246-259.

Research output: Contribution to journalArticle

Warner, GR, Li, ZL, Houde, ML, Atkinson, CE, Meling, DD, Chiang, C & Flaws, JA 2019, 'Ovarian metabolism of an environmentally relevant phthalate mixture', Toxicological Sciences, vol. 169, no. 1, pp. 246-259. https://doi.org/10.1093/toxsci/kfz047
Warner GR, Li ZL, Houde ML, Atkinson CE, Meling DD, Chiang C et al. Ovarian metabolism of an environmentally relevant phthalate mixture. Toxicological Sciences. 2019 Jan 1;169(1):246-259. https://doi.org/10.1093/toxsci/kfz047
Warner, Genoa R. ; Li, Zhong (Lucas) ; Houde, Madeline L. ; Atkinson, Cassandra E. ; Meling, Daryl D. ; Chiang, Catheryne ; Flaws, Jodi A. / Ovarian metabolism of an environmentally relevant phthalate mixture. In: Toxicological Sciences. 2019 ; Vol. 169, No. 1. pp. 246-259.
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