There are over 400 hypoxic zones in the ocean worldwide. Both laboratory and field studies have shown that hypoxia causes endocrine disruption and reproductive impairments in vertebrates. More importantly, our recent study discovered that parental (F0) hypoxia exposure resulted in the transgenerational impairment of sperm quality in the F2 generation through the epigenetic regulation of germ cells. In the present study, we aim to test the hypothesis that the brain, as the major regulator of the brain-pituitary-gonad (BPG) axis, is also involved in the observed transgenerational effect. Using comparative transcriptomic analysis on brain tissues of marine medaka Oryzias melastigma, 45 common differentially expressed genes caused by parental hypoxia exposure were found in the hypoxic group of the F0 and F2 generations, and the transgenerational groups of the F2 generation. The bioinformatic analysis on this deregulated gene cluster further highlighted the possible involvement of the brain in the transgenerational effect of hypoxia on testicular structure, including abnormal morphologies of the epididymis and the seminal vesicle, and degeneration of the seminiferous tubule. This finding is concordant to the result of hematoxylin and eosin staining, which showed the reduction of testicular lobular diameter in the F0 and F2 generations. Our study demonstrated for the first time the involvement of the brain in the transgenerational effect of hypoxia.

全世界海洋中有400多个缺氧区。实验室和现场研究都表明，缺氧会导致脊椎动物的内分泌紊乱和生殖功能受损。更重要的是，我们最近的研究发现，父母（F0）缺氧暴露通过生殖细胞的表观遗传调控导致F2代精子质量的跨代损伤。在本研究中，我们旨在检验以下假设：大脑作为脑垂体性腺（BPG）轴的主要调节剂，也参与了观察到的跨代效应。使用比较转录组学分析海洋（Myaka oryzias melastigma）的脑组织在F0和F2代的低氧组和F2代的跨代组中发现了45个由父母低氧暴露引起的常见差异表达基因。对这种失调的基因簇的生物信息学分析进一步强调了大脑可能参与缺氧对睾丸结构的跨代影响，包括附睾和精囊的异常形态以及生精小管的变性。这一发现与苏木精和曙红染色的结果一致，苏木精和曙红染色显示在F0和F2代中睾丸小叶直径的减小。我们的研究首次证明了大脑参与了低氧的代际效应。