title: Peroxisome proliferator-activated receptor α mediates di-(2-ethylhexyl) phthalate transgenerational repression of ovarian Esr1 expression in female mice.
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.
authors.affiliation: Research Center for Environmental Risk, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan; Department of Nursing, School of Health Sciences, Ibaraki Prefectural University of Health Science, Inashiki-gun, Ibaraki, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Kawano
authors.affiliation: Research Center for Environmental Risk, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
authors.forename: Xian-Yang
authors.initials: XY
authors.lastname: Qin
authors.affiliation: Division of Pathology, Biological Safety Research Center, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Animal Production Science, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: Research Center for Environmental Risk, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nansai
authors.affiliation: Pathophysiological Laboratory Sciences, Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Tamie
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Research Center for Environmental Risk, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan. Electronic address: hsone@nies.go.jp.
authors.forename: Hideko
authors.initials: H
authors.lastname: Sone
mesh_terms: D000818:Animals; D001141:Aromatase / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D015536:Down-Regulation; D052244:Endocrine Disruptors / Q000633:toxicity*; D047628:Estrogen Receptor alpha / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D005260:Female; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D047493:PPAR alpha / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D052244:Endocrine Disruptors; D047628:Estrogen Receptor alpha; D047493:PPAR alpha; D004051:Diethylhexyl Phthalate; D001141:Aromatase
keywords: DEHP; Female mice; PPARα; Reproductive; Transgenerational