Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
PLoS One. 2011;6(9):e24540. doi: 10.1371/journal.pone.0024540. Epub 2011 Sep 8.
As a global environmental concern, hypoxia is known to be associated with many biological and physiological impairments in aquatic ecosystems. Previous studies have mainly focused on the effect of hypoxia in adult animals. However, the effect of hypoxia and the underlying mechanism of how hypoxia affects embryonic development of aquatic animals remain unclear.
METHODOLOGY/PRINCIPAL FINDINGS: In the current study, the effect of hypoxia on primordial germ cell (PGC) migration in zebrafish embryos was investigated. Hypoxic embryos showed PGC migration defect as indicated by the presence of mis-migrated ectopic PGCs. Insulin-like growth factor (IGF) signaling is required for embryonic germ line development. Using real-time PCR, we found that the mRNA expression levels of insulin-like growth factor binding protein (IGFBP-1), an inhibitor of IGF bioactivity, were significantly increased in hypoxic embryos. Morpholino knockdown of IGFBP-1 rescued the PGC migration defect phenotype in hypoxic embryos, suggesting the role of IGFBP-1 in inducing PGC mis-migration.
CONCLUSIONS/SIGNIFICANCE: This study provides novel evidence that hypoxia disrupts PGC migration during embryonic development in fish. IGF signaling is shown to be one of the possible mechanisms for the causal link between hypoxia and PGC migration. We propose that hypoxia causes PGC migration defect by inhibiting IGF signaling through the induction of IGFBP-1.
作为一个全球性的环境问题，缺氧被认为与水生生态系统中的许多生物和生理损伤有关。先前的研究主要集中在成年动物缺氧的影响上。然而，缺氧对水生动物胚胎发育的影响及其潜在机制尚不清楚。
方法/主要发现：在本研究中，研究了缺氧对斑马鱼胚胎原始生殖细胞（PGC）迁移的影响。缺氧胚胎表现出 PGC 迁移缺陷，表现为异位 PGC 存在迁移错误。胰岛素样生长因子（IGF）信号对于胚胎生殖系发育是必需的。通过实时 PCR，我们发现缺氧胚胎中胰岛素样生长因子结合蛋白（IGFBP-1）的 mRNA 表达水平显著增加，IGFBP-1 是 IGF 生物活性的抑制剂。IGFBP-1 的 morpholino 敲低挽救了缺氧胚胎中 PGC 迁移缺陷表型，表明 IGFBP-1 在诱导 PGC 迁移错误中的作用。
结论/意义：这项研究提供了新的证据，表明缺氧在鱼类胚胎发育过程中破坏了 PGC 的迁移。IGF 信号被证明是缺氧与 PGC 迁移之间因果关系的可能机制之一。我们提出，缺氧通过诱导 IGFBP-1 抑制 IGF 信号来引起 PGC 迁移缺陷。
