Isoflurane inhibits embryonic stem cell self-renewal through retinoic acid receptor.
The commonly used inhalation anesthetic isoflurane could permeate rapidly through the placental barrier and induce toxicity to the central nervous system of the developing fetus. However, the effects of isoflurane in utero during early gestation are unknown. We therefore treated pregnant mice with 1.4% isoflurane for 2h per day for three days at day3.5 (E3.5) to day6.5 (E6.5) to investigated the toxicity of isoflurane. Pregnant mice were executed and the fetal mice were weighed and observed. Mouse ESCs (E14) was exposed to 2% isoflurane for 6h. Twenty-four hours later, self-renewal was examined with AP staining. Effects of isoflurane on the expression of RAR-γ were examined using Western blot. As a result, anesthesia with 1.4% isoflurane for 2 hour per day for 3 days reduced fetal growth and development. Isoflurane decreased self-renewal and the expression stemness genes (Nanog, Oct4, Sox2, and Lin28) in mESCs. Vitamin A attenuated the effects of isoflurane inducing self-renewal inhibition. In summary, Anesthesia with 1.4% isoflurane for 2h per day for 3 days reduced fetal growth and development. Moreover, isoflurane inhibits mESCs self-renewal through retinoic acid receptor.
Department of Anesthesiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
Sheng
S
Liu
Department of Anesthesiology, The Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200011, China.
Lei
L
Zhang
Department of Anesthesiology, Affiliated Hospital of Qingdao University, Qingdao University School of Medicine, Qingdao 266071, China.
Yi
Y
Liu
Department of Anesthesiology, The Eye, Ear, Nose and Throat Hospital of Fudan University, Shanghai Medical College of Fudan University, Shanghai, China.
Xia
X
Shen
Department of Anesthesiology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, 195 Tongbai Road, Zhengzhou City, Henan Province, 450007 China.
Longqiu
L
Yang
D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D015153:Blotting, Western; D000066673:Cell Self Renewal / Q000187:drug effects*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects*; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007530:Isoflurane / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D000097768:Retinoic Acid Receptor gamma
D018685:Anesthetics, Inhalation; D007530:Isoflurane; D018168:Receptors, Retinoic Acid; D000097768:Retinoic Acid Receptor gamma
Isoflurane; Mouse embryonic stem cell; Retinoic Acid Receptor; Self-renewal