Homozygous mutation of foxh1 arrests oogenesis causing infertility in female Nile tilapia†
Homozygous mutation of foxh1 arrests oogenesis causing infertility in female Nile tilapia†
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DOI：
10.1093/biolre/ioz225
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发表时间：
2019-12
影响因子：
3.6
通讯作者：
W. Tao;Hong‐Juan Shi;Jing Yang;Hamidou Diakite;T. Kocher;Deshou Wang
中科院分区：
文献类型：
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作者：
W. Tao;Hong‐Juan Shi;Jing Yang;Hamidou Diakite;T. Kocher;Deshou Wang
Foxh 1是Fox基因家族的成员之一，首次被鉴定为Smad蛋白复合物形成过程中的转录伴侣。最近的研究表明foxh 1在罗非鱼和小鼠卵母细胞的细胞质中高度表达。然而，其在卵子发生中的功能尚未被探索。在本研究中，通过CRISPR/Cas9创建了foxh 1-/-罗非鱼。在180 dah（孵化后的天数），foxh 1-/- XX鱼表现出卵子发生停滞和显着较低的GSI。卵母细胞从II期向III期的转变和卵泡细胞从一层向两层的转变受阻，导致突变体不育。转录组学分析显示，参与雌激素合成和卵母细胞生长的基因表达在foxh 1-/-卵巢中发生了改变。foxh 1的缺失导致Cyp 19 a1 a表达显著降低和Cyp 11b 2表达显著增加，这与血清雌二醇-17 β（E2）浓度显著降低和11-酮睾酮（11-KT）浓度升高一致。此外，E2的管理挽救了foxh 1-/- XX鱼的表型，所示的III期和IV期卵母细胞的外观和Cyp 11b 2的表达的情况下。综上所述，这些结果表明，foxh 1在卵母细胞中通过促进cyp 19 a1 a的表达来调节卵子发生，从而促进雌激素的产生。foxh 1基因的缺失可能会阻碍雌激素的合成和卵母细胞的生长，导致卵子发生停滞，从而导致罗非鱼不育。
Abstract Foxh1, a member of fox gene family, was first characterized as a transcriptional partner in the formation of the Smad protein complex. Recent studies have shown foxh1 is highly expressed in the cytoplasm of oocytes in both tilapia and mouse. However, its function in oogenesis remains unexplored. In the present study, foxh1–/– tilapia was created by CRISPR/Cas9. At 180 dah (days after hatching), the foxh1–/– XX fish showed oogenesis arrest and a significantly lower GSI. The transition of oocytes from phase II to phase III and follicle cells from one to two layers was blocked, resulting in infertility of the mutant. Transcriptomic analysis revealed that expression of genes involved in estrogen synthesis and oocyte growth were altered in the foxh1–/– ovaries. Loss of foxh1 resulted in significantly decreased Cyp19a1a and increased Cyp11b2 expression, consistent with significantly lower concentrations of serum estradiol-17β (E2) and higher concentrations of 11-ketotestosterone (11-KT). Moreover, administration of E2 rescued the phenotypes of foxh1–/– XX fish, as indicated by the appearance of phase III and IV oocytes and absence of Cyp11b2 expression. Taken together, these results suggest that foxh1 functions in the oocytes to regulate oogenesis by promoting cyp19a1a expression, and therefore estrogen production. Disruption of foxh1 may block the estrogen synthesis and oocyte growth, leading to the arrest of oogenesis and thus infertility in tilapia.