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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.
Reproductive Toxicology ( IF 3.3 ) Pub Date : 2020-05-11 , DOI: 10.1016/j.reprotox.2020.04.077
Naoko Jinno 1 , Ayako Furugen 1 , Yuko Kurosawa 1 , Yuki Kanno 1 , Katsuya Narumi 1 , Masaki Kobayashi 1 , Ken Iseki 1
Affiliation  

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.



中文翻译:

单次和重复丙戊酸给药对妊娠大鼠胎盘转运蛋白基因表达的影响:妊娠期分析。

众所周知,在怀孕期间使用丙戊酸 (VPA),一种抗癫痫药物,会增加各种胎儿风险。由于已知 VPA 可抑制组蛋白脱乙酰酶 (HDAC);它的管理可以改变基因转录水平。然而,在体内VPA 给药对胎盘转运蛋白的影响尚未完全阐明。本研究的目的是综合评价单次和重复VPA给药对胎盘转运蛋白表达的影响,并按孕日进行分析。我们研究了妊娠大鼠胎盘中的 18 个转运蛋白(8 个 ATP 结合盒 (ABC) 和 10 个溶质载体 (SLC) 转运蛋白),这些转运蛋白在中期或晚期口服 400 mg/kg/天 VPA 1 天或 4 天。妊娠。在对照大鼠中,4 个 ABC 转运蛋白基因(Abcb1a1bAbcc2Abcc4)上调,3 个(Abcc3Abcc5Abcg2) 通过妊娠下调,而 1 ( Abcc1 ) 没有改变。关于 SLC 转运蛋白,6 个基因(Slc7a5Slc16a3Slc22a3Slc22a4Slco2b1Slco4a1)增加,1 个(Slc29a1)在妊娠期间减少,而 3 个(Slc7a8Slc22a5Slco2a1)没有显着变化。单次 VPA 给药改变了 9 个转运蛋白的表达,重复给药改变了 13 个转运蛋白的表达。特别是,VPA 在妊娠晚期显着降低Abcc4Slc22a4并增加Abcc5在妊娠中期。我们的研究结果表明,VPA 给药改变了大鼠胎盘中转运蛋白的表达水平,并表明对 VPA 的敏感性在妊娠阶段有所不同。

更新日期:2020-05-11
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