Histological and Transcriptomic Analysis of Adult Japanese Medaka Sampled Onboard the International Space Station

To understand how humans adapt to the space environment, many experiments can be conducted on astronauts as they work aboard the Space Shuttle or the International Space Station (ISS). We also need animal experiments that can apply to human models and help prevent or solve the health issues we face in space travel. The Japanese medaka (Oryzias latipes) is a suitable model fish for studying space adaptation as evidenced by adults of the species having mated successfully in space during 15 days of flight during the second International Microgravity Laboratory mission in 1994. The eggs laid by the fish developed normally and hatched as juveniles in space. In 2012, another space experiment (“Medaka Osteoclast”) was conducted. Six-week-old male and female Japanese medaka (Cab strain osteoblast transgenic fish) were maintained in the Aquatic Habitat system for two months in the ISS. Fish of the same strain and age were used as the ground controls. Six fish were fixed with paraformaldehyde or kept in RNA stabilization reagent (n = 4) and dissected for tissue sampling after being returned to the ground, so that several principal investigators working on the project could share samples. Histology indicated no significant changes except in the ovary. However, the RNA-seq analysis of 5345 genes from six tissues revealed highly tissue-specific space responsiveness after a two-month stay in the ISS. Similar responsiveness was observed among the brain and eye, ovary and testis, and the liver and intestine. Among these six tissues, the intestine showed the highest space response with 10 genes categorized as oxidation–reduction processes (gene ontogeny term GO:0055114), and the expression levels of choriogenin precursor genes were suppressed in the ovary. Eleven genes including klf9, klf13, odc1, hsp70 and hif3a were upregulated in more than four of the tissues examined, thus suggesting common immunoregulatory and stress responses during space adaptation.

为探究人类如何适应太空环境，可在宇航员于航天飞机或国际空间站（International Space Station, ISS）执行任务期间开展多项实验。但我们同样需要适用于人类模型、能够帮助预防或解决太空飞行中面临的健康问题的动物实验。日本青鳉（Oryzias latipes）是研究太空适应的理想模式鱼类，1994年第二次国际微重力实验室任务中，该物种的成鱼在为期15天的太空飞行中成功交配，即可佐证这一点。此类鱼所产的卵可在太空环境中正常发育并孵化为幼体。2012年，另一项名为“青鳉破骨细胞（Medaka Osteoclast）”的太空实验顺利开展。研究人员将6周龄的雄性和雌性日本青鳉（Cab株成骨细胞转基因鱼）置于水生栖息地（Aquatic Habitat）系统中，在国际空间站内饲养了两个月。同期设置了相同品系、相同周龄的青鳉作为地面对照组。返回地面后，6尾青鳉经多聚甲醛固定，另有4尾置于RNA稳定试剂中保存（n=4），随后进行解剖以获取组织样本，以供该项目的多位首席研究员共享使用。组织学检测结果显示，除卵巢组织外，其余组织未出现显著变化。然而，对6种组织的5345个基因进行RNA测序（RNA-seq）分析后发现，在国际空间站停留两个月后，各组织呈现出高度特异性的太空响应特征。大脑与眼部、卵巢与睾丸，以及肝脏与肠道之间呈现出相似的响应模式。在这6种组织中，肠道的太空响应程度最高，共有10个基因被归类为氧化还原过程（gene ontogeny term GO:0055114）；卵巢组织中，绒膜蛋白原（choriogenin precursor）基因的表达水平受到抑制。包括klf9、klf13、odc1、hsp70及hif3a在内的11个基因在超过4种受试组织中出现上调，这表明在太空适应过程中存在共通的免疫调节与应激响应机制。