BRAIN GRAFTS OF MIGRATORY GNRH CELLS INDUCE GONADAL RECOVERY IN HYPOGONADAL (HPG) MICE

Gonadotropin-releasing hormone (GnRH) neurons are derived from the olfactory placode and migrate into the CNS during embryogenesis. During this migration the GnRH neuronal population follows a very specific pathway through the nasal septum and forebrain with individual neurons 'stopping' at various points along the way. Following migration GnRH neurons elaborate axonal projections, the major one to the median eminence. The function of this neurosecretory connection can then be assessed by activation of the pituitary-gonadal axis. In previous experiments we had demonstrated that grafted post-migratory GnRH neurons could send axons to the median eminence and initiate gonadal development in hypogonadal (hpg) mice that lack GnRH. In the present experiment, grafts derived from the embryonic nasal septum, which contains the migratory population of GnRH neurons, were used to determine if the transplanted GnRH neurons could (1) continue their migration in the adult host brain, (2) elaborate axons to their normal target in the host and (3) stimulate the host pituitary-gonadal axis to induce gonadal development. Nasal tissue from normal mouse embryos was implanted into the preoptic area (n = 8), anterior hypothalamus (n = 3) or third ventricle (n = 1) of adult hpg males. Following survival of 10 days to 10 weeks, the distribution of GnRH immunoreactive elements was assessed and testicular weight recorded. Surviving GnRH neurons were few in number and were found within the graft (n = 3), the host brain (n = 2) or both (n = 1). Four grafts resulted in specific outgrowth of GnRH axons through the host parenchyma to the median eminence. Three of the four animals with median eminence innervation had testicular development. These observations indicate that migratory GnRH neurons from the nasal septum retain a limited but real capacity to migrate in adult host brain. Furthermore, interruption of the normal migratory pathway of these neurons does not disrupt their potential for axonal growth, axonal pathfinding and the establishment of a functional neurosecretory connection with their normal target.