The great migration: How glial cells could regulate GnRH neuron development and shape adult reproductive life

In mammals, reproductive function is under the control of hypothalamic neurons named Gonadotropin-Releasing Hormone (GnRH) neurons. These neurons migrate from the olfactory placode to the brain, during embryonic development. For the past 40 years, these neurons have been considered an example of tangential migration, i.e., dependent on the olfactory/vomeronasal/terminal nerves. Numerous studies have highlighted the factors involved in the migration of these neurons but thus far overlooked the cellular microenvironment that produces them. Many of these factors are dysregulated in hypogonadotropic hypogonadism, resulting in subfertility/infertility. Nevertheless, over the past ten years, several papers have reported the influence of glial cells (named olfactory ensheathing cells [OECs]) in the migration and differentiation of GnRH neurons. This review will describe the atypical origins, migration, and differentiation of these neurons, focusing on the latest discoveries. There will be a more specific discussion on the involvement of OECs in the development of GnRH neurons, during embryonic and perinatal life; as well as on their potential implication in the development of congenital or idiopathic hypogonadotropic hypogonadism (such as Kallmann syndrome).