Amniotic fluid exerts a neurotrophic influence on fetal neurodevelopment via the ERK/GSK-3 pathway

Biological research: BR

Ki-Min Song¹  Won-Sik Shim²  Yongwoo Jang²  Sung Min Kim³  Eun-Kyung Kim⁴ 

[1] College of Pharmacy, Gachon University, Incheon, South Korea;College of Pharmacy, Seoul National University, Seoul, South Korea;Department of Health Sciences, Hanyang University, Seoul, South Korea;McLean Hospital, Harvard Medical School, Belmont, USA

关键词: Amniotic fluid;    Extracellular signal-regulated kinase (ERK);    Glycogen synthase kinase-3 (GSK-3);    Neural clustering;    Neurosphere;    Fetal development;   

DOI  :  10.1186/s40659-015-0029-4

学科分类：生物科学（综合）

来源: BioMed Central

【 摘 要 】

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. 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. 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.

【 授权许可】

CC BY