Data from: Development of the neurons controlling fertility in humans: new insights from 3D imaging and transparent fetal brains

Fertility in mammals is controlled by hypothalamic neurons that secrete
gonadotropin-releasing hormone (GnRH). These neurons differentiate in the
olfactory placodes during embryogenesis and migrate from the nose to the
hypothalamus before birth. Information regarding this process in humans is
sparse. Here, we adapted new tissue-clearing and whole-mount
immunohistochemical techniques to entire human embryos/fetuses to
meticulously study this system during the first trimester of gestation in
the largest series of human fetuses examined to date. Combining these
cutting-edge techniques with conventional immunohistochemistry, we provide
the first chronological and quantitative analysis of GnRH neuron origins,
differentiation and migration, as well as a 3D atlas of their distribution
in the fetal brain. We reveal not only that the number of
GnRH-immunoreactive neurons in humans is significantly higher than
previously thought, but that GnRH cells migrate into several
extrahypothalamic brain regions in addition to the hypothalamus. Their
presence in these areas raises the possibility that GnRH has
non-reproductive roles, creating new avenues for research on GnRH
functions in cognitive, behavioral and physiological processes.

哺乳动物的生殖功能由分泌促性腺激素释放激素（gonadotropin-releasing hormone, GnRH）的下丘脑神经元调控。这类神经元在胚胎发生（embryogenesis）阶段于嗅基板（olfactory placodes）中分化，并于出生前从鼻部迁移至下丘脑。目前针对人类该过程的研究数据仍较为匮乏。本研究针对完整人类胚胎/胎儿，改良了新型组织透明化技术（tissue-clearing）与全组织免疫组化技术（whole-mount immunohistochemical techniques），依托迄今规模最大的人类胎儿样本队列，对妊娠早期（first trimester of gestation）的该神经系统展开了细致探究。结合上述前沿技术与传统免疫组化方法，我们首次对GnRH神经元的起源、分化与迁移过程完成了时序性与定量分析，并构建了胎儿脑内该类神经元分布的三维图谱。研究不仅发现人类体内GnRH免疫阳性神经元的数量远高于此前认知，还证实GnRH细胞不仅会迁移至下丘脑，还会进入多个下丘脑外脑区。这类神经元在上述区域的存在提示，GnRH可能具备非生殖功能，为探索GnRH在认知、行为及生理过程中的功能开辟了全新研究方向。