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

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Title: Effects of single and repetitive valproic acid administration on the gene expression of placental transporters in pregnant rats : An analysis by gestational period.
Authors: Jinno, Naoki Browse this author
Furugen, Ayako Browse this author →KAKEN DB
Kurosawa, Yuko Browse this author
Kanno, Yuki Browse this author
Narumi, Katsuya Browse this author →KAKEN DB
Kobayashi, Masaki Browse this author →KAKEN DB
Iseki, Ken Browse this author →KAKEN DB
Keywords: ABC transporter
Antiepileptic drug
Gestational period
Placenta
Rat
SLC transporter
Valproic acid
Issue Date: 11-May-2020
Journal Title: Reproductive toxicology (Elmsford, N.Y.)
Volume: 96
Start Page: 47
End Page: 56
Publisher DOI: 10.1016/j.reprotox.2020.04.077
PMID: 32437819
Abstract: 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.
Rights: ©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/
(https://creativecommons.org/licenses/by-nc-nd/4.0/
Type: article (author version)
URI: http://hdl.handle.net/2115/81137
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 古堅 彩子

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