Gonadotropin Signaling in Zebrafish Ovary and Testis Development: Insights From Gene Knockout Study
Gonadotropin Signaling in Zebrafish Ovary and Testis Development: Insights From Gene Knockout Study
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DOI：
10.1210/me.2015-1126
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发表时间：
2015-12-01
影响因子：
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通讯作者：
Cheng, Christopher H. K.
中科院分区：
文献类型：
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作者：
Chu, Lianhe;Li, Jianzhen;Cheng, Christopher H. K.
利用转录激活因子样效应物核酸酶介导的基因敲除技术，我们之前已经证明，LH 信号对于斑马鱼的卵母细胞成熟和排卵是必需的，但对于睾丸发育来说是可有可无的。在这里，我们进一步建立了 fshb 和 fshr 敲除斑马鱼系。在雌性中，fshb 突变体是生育力低下的，而 fshr 突变体是不育的。在 fshb 突变体中，卵泡发生受到部分影响，但在 fshr 突变体中，卵泡发生在初级生长阶段完全停滞。在雄性中，fshb 和 fshr 突变体具有生育能力。受精率和睾丸的组织学结构不受影响。然而，fshb的双敲除； lhb 或 fshr； lhr 会导致所有不育的男性后代。在双敲除突变体（fshb；lhb 和 fshr；lhr）中，关键类固醇激素和类固醇生成基因显着减少，但在单敲除突变体（fshb、lhb、fshr 和 lhr）雄性中则没有。此外，我们还证明了斑马鱼中FSH受体（FSHR）和LH受体的组成活性，以及LH通过与fshb中的FSHR交叉反应的代偿作用； lhr双突变体，从而解释了在配体/受体突变体系中观察到的表型差异。综上所述，我们的数据建立了以下关于促性腺激素信号传导在斑马鱼性腺发育中的作用的模型。在女性中，FSH信号主要负责促进卵泡生长，而LH信号主要负责刺激卵母细胞成熟和排卵。在男性中，FSH 和 LH 信号传导的功能重叠，只有 FSH 和 LH 信号传导同时破坏才可能导致不育表型。在缺乏 FSH 的情况下，无论男性还是女性，LH 都可以通过与 FSHR 交叉反应发挥代偿作用。
Using the transcription activator-like effectors nucleases-mediated gene knockout technology, we have previously demonstrated that LH signaling is required for oocyte maturation and ovulation but is dispensable for testis development in zebrafish. Here, we have further established the fshb and fshr knockout zebrafish lines. In females, fshb mutant is subfertile, whereas fshr mutant is infertile. Folliculogenesis is partially affected in the fshb mutant but is completely arrested at the primary growth stage in the fshr mutant. In males, fshb and fshr mutant are fertile. The fertilization rate and histological structure of the testis is not affected. However, double knockout of fshb; lhb or fshr; lhr leads to all infertile male offspring. The key steroid hormones and steroidogenic genes are dramatically decreased in double knockout mutant (fshb; lhb and fshr; lhr) but not in single knockout mutant (fshb, lhb, fshr, and lhr) males. Furthermore, we have also demonstrated the constitutive activities of both FSH receptor (FSHR) and LH receptor in zebrafish and the compensatory role of LH by cross-reacting with FSHR in the fshb; lhr double mutant, thus explaining the phenotypic discrepancy observed among the ligand/receptor mutant lines. Taken together, our data established the following models on the roles of gonadotropin signaling in zebrafish gonad development. In females, FSH signaling is mainly responsible for promoting follicular growth, whereas LH signaling is mainly responsible for stimulating oocyte maturation and ovulation. In males, the functions of FSH and LH signaling overlap, and only disruption of both FSH and LH signaling could lead to the infertile phenotype. In the absence of FSH, LH could play a compensatory role by cross-reacting with FSHR in both male and female.