Mammalian reproductive success depends on gonadotrophin‐releasing hormone (GnRH) neurones to stimulate gonadotrophin secretion from the anterior pituitary and activate gonadal steroidogenesis and gametogenesis. Genetic screening studies in patients diagnosed with Kallmann syndrome (KS), a congenital form of hypogonadotrophic hypogonadism (CHH), identified several causal mutations, including those in the fibroblast growth factor (FGF) system. This signalling pathway regulates neuroendocrine progenitor cell proliferation, fate specification and cell survival. Indeed, the GnRH neurone system was absent or abrogated in transgenic mice with reduced (ie, hypomorphic) Fgf8 and/or Fgf receptor (Fgfr) 1 expression, respectively. Moreover, we found that GnRH neurones were absent in the embryonic olfactory placode of Fgf8 hypomorphic mice, the putative birthplace of GnRH neurones. These observations, together with those made in human KS/CHH patients, indicate that the FGF8/FGFR1 signalling system is a requirement for the ontogenesis of the GnRH neuronal system and function. In this review, we discuss how epigenetic factors control the expression of genes such as Fgf8 that are known to be critical for GnRH neurone ontogenesis, fate specification, and the pathogenesis of KS/CHH.

中文翻译：

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促性腺激素释放激素神经元发育和性腺营养不良性腺功能减退的表观基因组控制。

哺乳动物的生殖成功取决于促性腺激素释放激素（GnRH）神经元，以刺激垂体前叶分泌促性腺激素并激活性腺类固醇生成和配子生成。对确诊为先天性性腺功能减退性性腺机能减退（CHH）的Kallmann综合征（KS）患者的基因筛查研究确定了几种因果突变，包括成纤维细胞生长因子（FGF）系统中的突变。该信号传导途径调节神经内分泌祖细胞的增殖，命运规范和细胞存活。确实，在Fgf8和/或Fgf受体（Fgfr）1减少（即，亚同型）的转基因小鼠中，GnRH神经元系统不存在或被废除。表达式。此外，我们发现Fgf8亚型小鼠（GnRH神经元的假定出生地）的胚胎嗅觉斑中不存在GnRH神经元。这些观察结果以及在人KS / CHH患者中的观察结果表明，FGF8 / FGFR1信号系统是GnRH神经元系统和功能本体发育的必要条件。在这篇综述中，我们讨论了表观遗传因素如何控制诸如Fgf8之类的基因的表达，这些基因对于GnRH神经元的发生，命运规范以及KS / CHH的发病机理至关重要。