Effects of single and repetitive valproic acid administration on the gene expression of placental transporters in pregnant rats : An analysis by gestational period.

Jinno, Naoki; Furugen, Ayako; Kurosawa, Yuko; Kanno, Yuki; Narumi, Katsuya; Kobayashi, Masaki; Iseki, Ken

Effects of single and repetitive valproic acid administration on the gene expression of placental transporters in pregnant rats : An analysis by gestational period.

Jinno, Naoki; Furugen, Ayako; Kurosawa, Yuko et al.

Reproductive toxicology (Elmsford, N.Y.), 2020, 96, 47-56

Permalink : https://hdl.handle.net/2115/81137

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アクセス権	open access
URI	https://hdl.handle.net/2115/81137
タイトル	Effects of single and repetitive valproic acid administration on the gene expression of placental transporters in pregnant rats : An analysis by gestational period.
著者	Jinno, Naoki ; Furugen, Ayako ; Kurosawa, Yuko ; Kanno, Yuki ; Narumi, Katsuya ; Kobayashi, Masaki ; Iseki, Ken
著者名 Jinno, Naoki
e-Rad_Researcher 90767261 著者名 Furugen, Ayako
著者名 Kurosawa, Yuko
著者名 Kanno, Yuki
e-Rad_Researcher 90746752 著者名 Narumi, Katsuya
e-Rad_Researcher 70431319 著者名 Kobayashi, Masaki
e-Rad_Researcher 40203062 著者名 Iseki, Ken
言語	英語
キーワード	ABC transporter
	Antiepileptic drug
	Gestational period
	Placenta
	Rat
	SLC transporter
	Valproic acid
発行日	2020-05-11
収録物名	Reproductive toxicology (Elmsford, N.Y.)
巻(号)	96
ページ	47-56
抄録	The use of valproic acid (VPA), an antiepileptic drug, during pregnancy, is known to increase various fetal risks. Since VPA has been known to inhibit histone deacetylases (HDACs); its administration could alter gene transcription levels. However, in vivo effects of VPA administration on placental transporters have not been fully elucidated. The purpose of the present study was to comprehensively evaluate the effects of single and repetitive VPA administration on the expression of placental transporters and analyze them by gestational day. We investigated 18 transporters (8 ATP-binding cassette (ABC) and 10 solute carrier (SLC) transporters) in the placentas of pregnant rats that were orally administered 400 mg/kg/day VPA for one or four days, during mid- or late gestation. In the control rats, 4 ABC transporter genes (Abcb1a, 1b, Abcc2, Abcc4) were upregulated, 3 (Abcc3, Abcc5, Abcg2) downregulated through gestation, whereas 1 (Abcc1) was not changed. Regarding SLC transporters, 6 genes (Slc7a5, Slc16a3, Slc22a3, Slc22a4, Slco2b1, Slco4a1) were increased, 1 (Slc29a1) decreased through gestation, whereas 3 (Slc7a8, Slc22a5, Slco2a1) showed no significant change. Single VPA administration altered the expression of 9 transporters and repetitive administration, 13 transporters. In particular, VPA remarkably decreased Abcc4 and Slc22a4 in late gestation and increased Abcc5 during mid-gestation. Our findings indicated that VPA administration changed transporter expression levels in rat placenta, and suggested that sensitivity to VPA differs across gestational stages.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	©2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	1873-1708
関連情報	PMID 32437819
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.reprotox.2020.04.077