Conditional Fgfr1 Deletion in GnRH Neurons Leads to Minor Disruptions in the Reproductive Axis of Male and Female Mice.
Conditional Fgfr1 Deletion in GnRH Neurons Leads to Minor Disruptions in the Reproductive Axis of Male and Female Mice.
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DOI：
10.3389/fendo.2020.588459
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发表时间：
2020
影响因子：
5.2
通讯作者：
Tsai PS
中科院分区：
文献类型：
--
作者：
Dela Cruz C;Horton CA;Sanders KN;Andersen ND;Tsai PS
在人类和小鼠中，成纤维细胞生长因子受体1（Fgfr 1）的失活突变导致促性腺激素释放激素（GnRH）缺乏和下游生殖障碍。目前尚不清楚Fgfr 1信号直接作用于GnRH神经元是否决定性地驱动了功能性GnRH系统的建立。为了回答这个问题，我们使用Cre/loxP方法在GnRH神经元中产生了Fgfr 1条件性缺失的小鼠模型。这些小鼠被称为Fgfr 1cKO小鼠，与对照小鼠一起沿着检查其青春期开始和许多生殖轴功能。我们的研究结果表明，Fgfr 1cKO小鼠在GnRH系统和青春期开始时没有可检测到的缺陷，垂体功能仅发生细微变化，但在25日龄时表现出明显的睾丸和卵巢形态学破坏，表明年轻时配子发生受损。然而，这些干扰是短暂的，在老年小鼠中无法检测到。我们的研究结果表明，Fgfr 1信号直接对GnRH神经元的支持，在一定程度上，生殖轴的功能，导致青春期的早期阶段，但不是关键需要青春期的开始或性成熟动物的生殖维持。
In humans and mice, inactivating mutations in fibroblast growth factor receptor 1 (Fgfr1) lead to gonadotropin-releasing hormone (GnRH) deficiency and a host of downstream reproductive disorders. It was unclear if Fgfr1 signaling directly upon GnRH neurons critically drove the establishment of a functional GnRH system. To answer this question, we generated a mouse model with a conditional deletion of Fgfr1 in GnRH neurons using the Cre/loxP approach. These mice, called Fgfr1cKO mice, were examined along with control mice for their pubertal onset and a host of reproductive axis functions. Our results showed that Fgfr1cKO mice harbored no detectable defects in the GnRH system and pubertal onset, suffered only subtle changes in the pituitary function, but exhibited significantly disrupted testicular and ovarian morphology at 25 days of age, indicating impaired gametogenesis at a young age. However, these disruptions were transient and became undetectable in older mice. Our results suggest that Fgfr1 signaling directly on GnRH neurons supports, to some extent, the reproductive axis function in the period leading to the early phase of puberty, but is not critically required for pubertal onset or reproductive maintenance in sexually mature animals.