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Effects of valproic acid on syncytialization in human placental trophoblast cell lines
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| Title: | Effects of valproic acid on syncytialization in human placental trophoblast cell lines |
| Authors: | Nanami, Ohyama Browse this author | | Ayako, Furugen Browse this author →KAKEN DB | | Riko, Sawada Browse this author | | Ryoichi, Aoyagi Browse this author | | Ayako, Nishimura Browse this author | | Takeshi, Umazume Browse this author →KAKEN DB | | Katsuya, Narumi Browse this author →KAKEN DB | | Masaki, Kobayashi Browse this author →KAKEN DB |
| Keywords: | Antiepileptic drug | | Differentiation | | Placenta | | Syncytialization | | Trophoblast | | Valproic Acid |
| Issue Date: | 1-Sep-2023 |
| Publisher: | Elsevier |
| Journal Title: | Toxicology and Applied Pharmacology |
| Volume: | 474 |
| Start Page: | 116611 |
| Publisher DOI: | 10.1016/j.taap.2023.116611 |
| PMID: | 37385477 |
| Abstract: | The placenta is a critical organ for fetal development and a healthy pregnancy, and has multifaceted functions (e.g., substance exchange and hormone secretion). Syncytialization of trophoblasts is important for maintaining placental functions. Epilepsy is one of the most common neurological conditions worldwide. Therefore, this study aimed to reveal the influence of antiepileptic drugs, including valproic acid (VPA), carbamazepine, lamotrigine, gabapentin, levetiracetam, topiramate, lacosamide, and clobazam, at clinically relevant concentrations on syncytialization using in vitro models of trophoblasts. To induce differentiation into syncytiotrophoblast-like cells, BeWo cells were treated with forskolin. Exposure to VPA was found to dose-dependently influence syncytialization-associated genes (ERVW-1, ERVFRD-1, GJA1, CGB, CSH, SLC1A5, and ABCC4) in differentiated BeWo cells. Herein, the biomarkers between differentiated BeWo cells and the human trophoblast stem model (TS) were compared. In particular, MFSD2A levels were low in BeWo cells but abundant in TS cells. VPA exposure affected the expression of ERVW-1, ERVFRD-1, GJA1, CSH, MFSD2A, and ABCC4 in differentiated cells (ST-TS). Furthermore, VPA exposure attenuated BeWo and TS cell fusion. Finally, the relationships between neonatal/placental parameters and the expression of syncytialization markers in human term placentas were analyzed. MFSD2A expression was positively correlated with neonatal body weight, head circumference, chest circumference, and placental weight. Our findings have important implications for better understanding the mechanisms of toxicity of antiepileptic drugs and predicting the risks to placental and fetal development. |
| Rights: | © 2023. 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/2115/93037 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 古堅 彩子
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