Jang Yongwoo, Kim Eun-Kyung, Shim Won-Sik, Song Ki-Min, Kim Sung Min
College of Pharmacy, Seoul National University, Seoul, 151-742, South Korea.
McLean Hospital, Harvard Medical School, Belmont, MA, 02478, USA.
Biol Res. 2015 Aug 5;48(1):44. doi: 10.1186/s40659-015-0029-4.
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.
胎儿被孕母羊膜囊中所含的羊水（AF）所包围。孕期AF直接输送给胎儿。尽管最近有报道称AF是一种含有多种物质的未开发资源，但AF是否会影响胎儿神经发育仍不清楚。
我们使用从怀孕16天的SD大鼠胚胎中提取的AF，并将其作用于同一大鼠胚胎来源的神经细胞。我们发现，将AF作用于皮质神经元会增加胎儿神经发育所必需的ERK1/2磷酸化，而MEK抑制剂处理可抑制这种磷酸化。此外，我们发现随后糖原合酶激酶-3（GSK-3）受到抑制，GSK-3是神经细胞中细胞命运的重要决定因素。实际上，AF增加了皮质神经元的神经聚集，这表明聚集的细胞是增殖的神经祖细胞。因此，我们证实了AF通过形成神经球来增加神经祖细胞的能力。此外，我们表明ERK/GSK-3信号通路参与了AF介导的神经球扩大。
尽管胎盘主要为胎儿发育提供含氧血液和营养物质，但这些发现进一步表明，孕期循环进入胎儿体内的AF可能通过丝裂原活化蛋白激酶衍生的GSK-3信号通路影响胎儿神经发育。此外，我们认为AF可作为再生医学领域的宝贵资源。
