The Role of Kisspeptin in the Pathogenesis of Pregnancy Complications: A Narrative Review

Abstract

Kisspeptins are the family of neuropeptide products of the KISS-1 gene that exert the biological action by binding with the G-protein coupled receptor 54 (GPR54), also known as the KISS-1 receptor. The kisspeptin level dramatically increases during pregnancy, and the placenta is supposed to be its primary source. The role of kisspeptin has already been widely studied in hypogonadotropic hypogonadism, fertility, puberty disorders, and insulin resistance-related conditions, including type 2 diabetes mellitus, polycystic ovary syndrome, and obesity. Gestational diabetes mellitus (GDM), preeclampsia (PE), preterm birth, fetal growth restriction (FGR), or spontaneous abortion affected 2 to 20% of pregnancies worldwide. Their occurrence is associated with numerous short and long-term consequences for mothers and newborns; hence, novel, non-invasive predictors of their development are intensively investigated. The study aims to present a comprehensive review emphasizing the role of kisspeptin in the most common pregnancy-related disorders and neonatal outcomes. The decreased level of kisspeptin is observed in women with GDM, FGR, and a high risk of spontaneous abortion. Nevertheless, there are still many inconsistencies in kisspeptin concentration in pregnancies with preterm birth or PE. Further research is needed to determine the usefulness of kisspeptin as an early marker of gestational and neonatal complications.

Placental mRNA Expression of Neurokinin B Is Increased in PCOS Pregnancies with Female Offspring

“…KISS1 and NKB are increased in pregnancy as a result of placental production. Although the role of kisspeptin in regulating trophoblast invasion and embryo implantation is established [15], little is known regarding the function of NKB in normal pregnancy [14]. Kisspeptins may have a role in the pathogenesis of GDM, as lower KISS1 plasma levels and higher placental protein expression of KISS1 and the kisspeptin-1 receptor have been found in women with GDM [60,61].…”

“…Their role is fundamental in puberty initiation, and they are also involved in the disturbed hypothalamic-pituitary function characterizing PCOS [12,13]. KISS1 and NKB levels increase in pregnancy due to placental production, and these peptides along with neurokinin receptors have been implicated in the pathogenesis of several pregnancy complications (PE, gestational diabetes, intrauterine growth restriction (IUGR), and preterm delivery) [14,15]. However, studies regarding the expression of these peptides in the human placenta in PCOS are lacking.…”

Epigenetics of Hypogonadotropic Hypogonadism: Molecular Mimicry between Severe Acute Respiratory Syndrome Coronavirus 2 and KISSR

“…The human kisspeptin protein (here referred to as KISS1) and the human kisspeptin receptor protein (here referred to as KISSR) form the hypothalamic system that regulates the gonadotropic axis at puberty and in adulthood. 1 As reviewed by Szydełko-Gorzkowicz et al, 2 KISS1 and KISSR participate in different biological processes in that KISS1 plays an essential role in governing pubertal onset and human reproduction, while alterations of KISSR are responsible for the development of hypogonadotropic hypogonadism syndrome that includes dysfunction of fertility, absent or incomplete sexual maturation, and puberty disorders. 3 4…”

Assessment of kisspeptin and trappin level in Iraqi women with early pregnancy loss: a cross sectional study

“…Around the world, pregnancy-related diabetes mellitus, pulmonary embolism (PE), premature delivery, neonatal growth retardation, or spontaneous abortion impacts roughly 20% of pregnant women. 18 Serum and plasma are used in clinical assays; however, the serum is more sensitive for biomarker detection. 19 Serum kisspeptin levels have been reported to be minimal in non-pregnant individuals but are significantly elevated in viable pregnancies.…”