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Sevoflurane inhibits embryonic stem cell self-renewal and subsequent neural differentiation by modulating the let-7a-Lin28 signaling pathway.
Cell Tissue Res. 2016 08; 365(2):319-30.CT

Abstract

The commonly used inhalational anesthetic, sevoflurane, can cause toxicity to the central nervous system of the developing fetus. Lin28 has been reported to regulate let-7a, thereby modulating embryo development, neurodegeneration, and even neuron-related tumorigenesis. We demonstrate that pregnant mice receiving sevoflurane treatment during the early stage of pregnancy give birth to fewer offspring presenting a lower birth weight. We have also treated mouse embryonic stem cells (mESCs) with sevoflurane for 6 h and determined that mESCs self-renewal is repressed, and that differentiation is initiated earlier than in controls. We have induced neural differentiation in the treated mESCs and determined that their neurogenesis is weakened. Furthermore, sevoflurane upregulates the level of let-7a, which might repress mESC self-renewal by directly targeting the Lin28 3'-untranslated region. Lin28 overexpression attenuates the influence of sevoflurane or of let-7a on the self-renewal of mESCs and their subsequent neural differentiation. The let-7a inhibitor also abolishes the influence of sevoflurane. Thus, the let-7a-Lin28 pathway is involved in the sevoflurane-induced inhibition of ESC self-renewal and subsequent neurogenesis. Our study demonstrates the molecular mechanism underlying the side effects of sevoflurane during early development, laying the foundation for studies on the safe and reasonable usage of other inhalational anesthetics.

Authors+Show Affiliations

Department of Anesthesiology, The Eye, Ear, Nose and Throat Hospital, Fudan University, Building No.9, 83 Fenyang Road, Xuhui District, Shanghai, 200031, China.Department of Anesthesiology, The Eye, Ear, Nose and Throat Hospital, Fudan University, Building No.9, 83 Fenyang Road, Xuhui District, Shanghai, 200031, China.Department of Anesthesiology, The Eye, Ear, Nose and Throat Hospital, Fudan University, Building No.9, 83 Fenyang Road, Xuhui District, Shanghai, 200031, China.Department of Anesthesiology, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China. xuzg1998@126.com.Department of Anesthesiology, The Eye, Ear, Nose and Throat Hospital, Fudan University, Building No.9, 83 Fenyang Road, Xuhui District, Shanghai, 200031, China. wenxianli66@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27022747

Citation

Yi, Xiuwen, et al. "Sevoflurane Inhibits Embryonic Stem Cell Self-renewal and Subsequent Neural Differentiation By Modulating the let-7a-Lin28 Signaling Pathway." Cell and Tissue Research, vol. 365, no. 2, 2016, pp. 319-30.
Yi X, Cai Y, Zhang N, et al. Sevoflurane inhibits embryonic stem cell self-renewal and subsequent neural differentiation by modulating the let-7a-Lin28 signaling pathway. Cell Tissue Res. 2016;365(2):319-30.
Yi, X., Cai, Y., Zhang, N., Wang, Q., & Li, W. (2016). Sevoflurane inhibits embryonic stem cell self-renewal and subsequent neural differentiation by modulating the let-7a-Lin28 signaling pathway. Cell and Tissue Research, 365(2), 319-30. https://doi.org/10.1007/s00441-016-2394-x
Yi X, et al. Sevoflurane Inhibits Embryonic Stem Cell Self-renewal and Subsequent Neural Differentiation By Modulating the let-7a-Lin28 Signaling Pathway. Cell Tissue Res. 2016;365(2):319-30. PubMed PMID: 27022747.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sevoflurane inhibits embryonic stem cell self-renewal and subsequent neural differentiation by modulating the let-7a-Lin28 signaling pathway. AU - Yi,Xiuwen, AU - Cai,Yirong, AU - Zhang,Nan, AU - Wang,Qingxiu, AU - Li,Wenxian, Y1 - 2016/03/29/ PY - 2015/09/12/received PY - 2016/02/19/accepted PY - 2016/3/30/entrez PY - 2016/3/30/pubmed PY - 2017/5/16/medline KW - Mouse embryonic stem cell KW - Neurogenesis KW - Self-renewal KW - Sevoflurane KW - let-7a-Lin28 pathway SP - 319 EP - 30 JF - Cell and tissue research JO - Cell Tissue Res. VL - 365 IS - 2 N2 - The commonly used inhalational anesthetic, sevoflurane, can cause toxicity to the central nervous system of the developing fetus. Lin28 has been reported to regulate let-7a, thereby modulating embryo development, neurodegeneration, and even neuron-related tumorigenesis. We demonstrate that pregnant mice receiving sevoflurane treatment during the early stage of pregnancy give birth to fewer offspring presenting a lower birth weight. We have also treated mouse embryonic stem cells (mESCs) with sevoflurane for 6 h and determined that mESCs self-renewal is repressed, and that differentiation is initiated earlier than in controls. We have induced neural differentiation in the treated mESCs and determined that their neurogenesis is weakened. Furthermore, sevoflurane upregulates the level of let-7a, which might repress mESC self-renewal by directly targeting the Lin28 3'-untranslated region. Lin28 overexpression attenuates the influence of sevoflurane or of let-7a on the self-renewal of mESCs and their subsequent neural differentiation. The let-7a inhibitor also abolishes the influence of sevoflurane. Thus, the let-7a-Lin28 pathway is involved in the sevoflurane-induced inhibition of ESC self-renewal and subsequent neurogenesis. Our study demonstrates the molecular mechanism underlying the side effects of sevoflurane during early development, laying the foundation for studies on the safe and reasonable usage of other inhalational anesthetics. SN - 1432-0878 UR - https://www.unboundmedicine.com/medline/citation/27022747/Sevoflurane_inhibits_embryonic_stem_cell_self_renewal_and_subsequent_neural_differentiation_by_modulating_the_let_7a_Lin28_signaling_pathway_ L2 - https://dx.doi.org/10.1007/s00441-016-2394-x DB - PRIME DP - Unbound Medicine ER -