title: Sevoflurane inhibits the self-renewal of mouse embryonic stem cells via the GABAAR-ERK signaling pathway.
abstract: A large number of pregnant women are exposed to inhalation anesthetics for non‑obstetric surgery. Previous studies have demonstrated the toxicity to the developing fetus caused by the inhalation anesthetic sevoflurane, which can permeate rapidly through the placental barrier. However, the mechanism of embryotoxicity remains largely unknown. The present study used mouse embryonic stem cells (mES cells) as an early development model, in order to investigate the mechanism underlying the embryo toxicity of sevoflurane and found that sevoflurane inhibited the self‑renewal of mES cells. Sevoflurane was shown to upregulate the level of phosphorylated extracellular signal‑regulated kinase (p‑ERK) but it did not affect the total expression of ERK by γ-aminobutyric acid A receptor (GABAAR). Knockdown of the GABAAR rescued the upregulation of p‑ERK and inhibition of self‑renewal induced by sevoflurane in mES cells. Additionally, inhibition of the activity of ERK signaling can rescue the influence of sevoflurane on mES cells. In conclusion, sevoflurane inhibited the self‑renewal of mES cells by GABAAR/ERK signaling, which may be a potential therapeutic target to prevent the embryotoxicity of sevoflurane.
authors.affiliation: Department of Anesthesiology, Subei People's Hospital of Jiangsu (Clinical Medical College of Yangzhou University), Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Liuqing
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Subei People's Hospital of Jiangsu (Clinical Medical College of Yangzhou University), Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Department of Anesthesiology, Subei People's Hospital of Jiangsu (Clinical Medical College of Yangzhou University), Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Shunyan
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, Subei People's Hospital of Jiangsu (Clinical Medical College of Yangzhou University), Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Xiangzhi
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of Scientific Research, Subei People's Hospital of Jiangsu (Clinical Medical College of Yangzhou University), Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Loujing
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, Subei People's Hospital of Jiangsu (Clinical Medical College of Yangzhou University), Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Ju
authors.initials: J
authors.lastname: Gao
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000066673:Cell Self Renewal / Q000187:drug effects* / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D008738:Methyl Ethers / Q000494:pharmacology*; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D034741:RNA, Small Interfering; D011963:Receptors, GABA-A; D000077149:Sevoflurane; D048049:Extracellular Signal-Regulated MAP Kinases