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 extra-hypothalamic brain regions in addition to the hypothalamus. Their presence in these areas raises the possibility that GnRH plays non-reproductive functions, creating new avenues for research on GnRH functions in cognitive, behavioral and physiological processes.

哺乳动物的生育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育阶段于嗅基板中分化，并在出生前从鼻腔迁移至下丘脑。目前针对人类该发育过程的研究资料仍较为稀缺。本研究针对完整人类胚胎/胎儿，优化了新型组织透明化与整体免疫组织化学技术，并依托迄今为止规模最大的人类胎儿样本队列，对妊娠早期阶段的该神经系统进行了细致剖析。本研究将这些前沿技术与传统免疫组织化学方法相结合，首次对GnRH神经元的起源、分化及迁移过程进行了时序性与定量分析，并构建了胎儿大脑内其分布的三维图谱。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细胞除迁移至下丘脑外，还会进入多个下丘脑外脑区。这些神经元在上述区域的存在，提示GnRH可能具备非生殖功能，这为研究GnRH在认知、行为及生理过程中的作用开辟了全新的研究方向。