Heterogeneity in GnRH and kisspeptin neurons and their significance in vertebrate reproductive biology

Vertebrate reproduction is essentially controlled by the hypothalamus-pituitary–gonadal (HPG) axis, which is a central dogma of reproductive biology. Two major hypothalamic neuroendocrine cell groups containing gonadotropin-releasing hormone (GnRH) and kisspeptin are crucial for control of the HPG axis in vertebrates. GnRH and kisspeptin neurons exhibit high levels of heterogeneity including their cellular morphology, biochemistry, neurophysiology and functions. However, the molecular foundation underlying heterogeneities in GnRH and kisspeptin neurons remains unknown. More importantly, the biological and physiological significance of their heterogeneity in reproductive biology is poorly understood. In this review, we first describe the recent advances in the neuroendocrine functions of kisspeptin-GnRH pathways. We then view the recent emerging progress in the heterogeneity of GnRH and kisspeptin neurons using morphological and single-cell transcriptomic analyses. Finally, we discuss our views on the significance of functional heterogeneity of reproductive endocrine cells and their potential relevance to reproductive health.