title: Amniotic fluid exerts a neurotrophic influence on fetal neurodevelopment via the ERK/GSK-3 pathway.
abstract: BACKGROUND
  The fetus is surrounded by the amniotic fluid (AF) contained by the amniotic sac of the pregnant female. The AF is directly conveyed to the fetus during pregnancy. Although AF has recently been reported as an untapped resource containing various substances, it remains unclear whether the AF could influence fetal neurodevelopment.
  
  
  RESULTS
  We used AF that was extracted from embryos at 16 days in pregnant SD rat and exposed the AF to the neural cells derived from the embryos of same rat. We found that the treatment of AF to cortical neurons increased the phosphorylation in ERK1/2 that is necessary for fetal neurodevelopment, which was inhibited by the treatment of MEK inhibitors. Moreover, we found the subsequent inhibition of glycogen synthase kinase-3 (GSK-3), which is an important determinant of cell fate in neural cells. Indeed, AF increased the neural clustering of cortical neurons, which revealed that the clustered cells were proliferating neural progenitor cells. Accordingly, we confirmed the ability of AF to increase the neural progenitor cells through neurosphere formation. Furthermore, we showed that the ERK/GSK-3 pathway was involved in AF-mediated neurosphere enlargement.
  
  
  CONCLUSIONS
  Although the placenta mainly supplies oxygenated blood, nutrient substances for fetal development, these findings further suggest that circulating-AF into the fetus could affect fetal neurodevelopment via MAP kinases-derived GSK-3 pathway during pregnancy. Moreover, we suggest that AF could be utilized as a valuable resource in the field of regenerative medicine.
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, 151-742, South Korea. biocorea@gmail.com.|McLean Hospital, Harvard Medical School, Belmont, MA, 02478, USA. biocorea@gmail.com.
authors.forename: Yongwoo
authors.initials: Y
authors.lastname: Jang
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, 151-742, South Korea. eunk0112@gmail.com.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Gachon University, Incheon, 406-840, South Korea. wsshim@gachon.ac.kr.
authors.forename: Won-Sik
authors.initials: WS
authors.lastname: Shim
authors.affiliation: Department of Health Sciences, Hanyang University, Seoul, 133-791, South Korea. haieung@hanyang.ac.kr.
authors.forename: Ki-Min
authors.initials: KM
authors.lastname: Song
authors.affiliation: Department of Physical Education, College of Performing Arts and Sport, Hanyang University, Seoul, 133-791, South Korea. minarthur@hanyang.ac.kr.
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Kim
mesh_terms: D000653:Amniotic Fluid / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology
chemical_list: D038362:Glycogen Synthase Kinase 3