The Role of Kisspeptin Signaling in the Physiology and Pathophysiology of Early Human Pregnancy

Kisspeptin, the product of the KISS1 gene and a ligand of the G-protein coupled receptor, KISS1R (also known as GPR54), is a relatively well-known hypothalamic neurohormone, the secretion of which is intrinsically linked to the kisspeptin, neurokinin B, and dynorphin (KNDy) neurons and is involved in the neuromodulation of gonadotropin-releasing hormone (GnRH) secretion, playing a key role in the central mechanism controlling the hypothalamic‒pituitary‒gonadal (HPG) axis. In contrast to our knowledge of the importance of kisspeptin neuronal signaling in regulating the onset of puberty and the control of fertility through its effects on the menstrual cycle, the importance of the extraneuronal pool of this hormone after fertilization and during early human pregnancy is far less complete. The very significant increase in the serum extrahypothalamic kisspeptin concentration in the first trimester of pregnancy, which originates from peripheral reproductive tissues, is accompanied by changes in local KISS1R expression. These findings suggest an important role of kisspeptin in the regulation of embryo implantation, trophoblast invasion, placentation and early pregnancy. The aim of this review is to present the current state of knowledge regarding the involvement of kisspeptin signaling in the physiology and pathophysiology of early pregnancy in humans. The diagnostic value of kisspeptin levels for early pregnancy outcomes will also be explored to identify potential related therapeutic targets.