S9.3 - Non-canonical effects of non-reproductive factors on reproduction

Abstract

The hypothalamic-pituitary-gonadal axis (HPG) controls pubertal development, sexual maturation, and fertility. We identified a role of hypothalamic microglia in controlling the HPG axis through Rank signaling. Whole-body and microglia Rank depletion led to hypogonadotropic hypogonadism (HH) resulting from an alteration in gonadotropin-releasing hormone (GnRH) neuron function. In addition, we identified rare gene variants of RANK in patients with HH. Transcriptional profiling upon Rank loss revealed defective microglia activation and morphological alterations in the median eminence, decreasing the contacts and engulfment of GnRH terminal projections and impairing GnRH neuronal responses to kisspeptin. Overall, our data uncover the microglia as regulator of GnRH neuronal function through Rank signaling, with potential implications for reproductive maturation and fertility Dra. Eva Gonzalez is PhD in Molecular Biology, is a Senior scientist and group leader of the Transformation and Metastasis laboratory, at the Spanish National Cancer Research Center (CNIO) in Madrid, Spain.