葉酸是胚胎發育的必需營養素。葉酸補充已知可增進肺部功能及降低神經管缺陷、慢性肺部阻塞、眼球變小的風險。懷孕婦女過量的葉酸補充會增加支氣管炎及氣喘的風險。然而對於葉酸如何參與在這些發育缺陷及疾病的作用機轉尚未完全了解。斑馬魚是一個研究胚胎發育有利的動物模式。在本實驗中我們利用超表現γ-穀氨酸水解酶來製造葉酸缺乏的斑馬魚動物模式。我們發現在葉酸缺乏的斑馬魚胚胎中展現了魚膘無法充氣、眼球變小及視力喪失的徵狀。這些發育的缺陷皆可藉由補充葉酸來恢復。我們的研究結果顯示增加半胱胺酸蛋白酶L/半胱胺酸蛋白酶抑制劑B的比例、影響核甘酸合成及降低維生素A酸的合成可能分別參與在魚膘無法充氣、眼球變小及視力喪失的徵狀中。以上的結果也顯示這個葉酸缺乏的斑馬魚胚胎能發展成肺氣腫及小眼畸形的藥物篩選平台。

Folate, vitamin B9, is an essential nutrient in embryonic development. Folate fortification enhances lung function and decreases the risk of neural tube defect, chronic obstructive pulmonary disease and small eye. Excessive folate supplementation in pregnant women increases the risk of the bronchiolitis and athma. However, the possible mechanisms of how folate participated in these malformations remain unknown. Zebrafish is a powerful animal model for embryogenesis. In this study, zebrafish embryo with folate deficiency is induced by overexpressing γGH protein. We found that folate deficient embryo displayed swimbladder deflation, small eye and vision loss. These phenotypic abnormalities were reversed by folate fortification. Our results suggested that increased ratio of cathepsin L/cystatin B-like, impaired nucleotide synthesis and reduced aldh1a3 expression were likely to be involved in the occurrence of swimbladder deflation, small eye and vision loss, respectively. Our results also suggested that this folate deficient model may serve as a drug-screening platform of emphysema and microphthalmia.

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