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  • Peroxisome proliferator-activated receptor α mediates di-(2-ethylhexyl) phthalate transgenerational repression of ovarian Esr1 expression in female mice.

Peroxisome proliferator-activated receptor α mediates di-(2-ethylhexyl) phthalate transgenerational repression of ovarian Esr1 expression in female mice.

Toxicology letters (2014-05-09)
Michihiro Kawano, Xian-Yang Qin, Midori Yoshida, Tomokazu Fukuda, Hiroko Nansai, Yumi Hayashi, Tamie Nakajima, Hideko Sone
ABSTRACT

Di-(2-ethylhexyl)-phthalate (DEHP) is a phthalate ester that binds peroxisome proliferator-activated receptor α (PPARα) to induce proliferation of peroxisomes and regulate the expression of specific target genes. The question of whether the effect of DEHP on female reproductive processes is mediated via PPARα-dependent signaling is controversial. In this study, we investigated the effect of exposure to DEHP on ovarian expression of estrogen receptor α (Esr1) and aromatase (Cyp19a1) in three generations of Sv/129 wild-type (WT, +/+) and PPARα (-/-) knockout mice. Compared with untreated controls, ovarian expression of Esr1 decreased in response to DEHP treatment in the F0 (0.56-fold, P=0.19), F1 (0.45-fold, P=0.023), and F2 (0.35-fold, P=0.014) generations of WT mice, but not PPARα-null mice. Our data indicate that transgenerational repression by DEHP of ovarian Esr1 gene expression is mediated by PPARα-dependent pathways. Further studies are required to elucidate the mechanisms underlying crosstalk between PPARα and Esr1 signaling in reproductive processes.

MATERIALS
Product Number
Brand
Product Description

Supelco
Bis(2-ethylhexyl) phthalate, Selectophore
Supelco
Bis(2-ethylhexyl) phthalate, PESTANAL®, analytical standard
Sigma-Aldrich
Dioctyl phthalate, ≥99.5%
Supelco
Bis(2-ethylhexyl) phthalate, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Supelco
Bis(2-ethylhexyl) phthalate solution, certified reference material, 2000 μg/mL in methanol
Plastic additive 01, European Pharmacopoeia (EP) Reference Standard