Kisspeptin in the Prediction of Pregnancy Complications

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2022 Aug 5

PMID 35928889

Authors

Jovanna Tsoutsouki

Bijal Patel

Alexander N Comninos

Waljit S Dhillo

Ali Abbara

Affiliations

Soon will be listed here.

Abstract

Kisspeptin and its receptor are central to reproductive health acting as key regulators of the reproductive endocrine axis in humans. Kisspeptin is most widely recognised as a regulator of gonadotrophin releasing hormone (GnRH) neuronal function. However, recent evidence has demonstrated that kisspeptin and its receptor also play a fundamental role during pregnancy in the regulation of placentation. Kisspeptin is abundantly expressed in syncytiotrophoblasts, and its receptor in both cyto- and syncytio-trophoblasts. Circulating levels of kisspeptin rise dramatically during healthy pregnancy, which have been proposed as having potential as a biomarker of placental function. Indeed, alterations in kisspeptin levels are associated with an increased risk of adverse maternal and foetal complications. This review summarises data evaluating kisspeptin's role as a putative biomarker of pregnancy complications including miscarriage, ectopic pregnancy (EP), preterm birth (PTB), foetal growth restriction (FGR), hypertensive disorders of pregnancy (HDP), pre-eclampsia (PE), gestational diabetes mellitus (GDM), and gestational trophoblastic disease (GTD).

Citing Articles

Renal autocrine neuropeptide FF (NPFF) signaling regulates blood pressure.

Lee H, Amatya B, Villar V, Asico L, Jeong J, Feranil J Sci Rep. 2024; 14(1):15407.

PMID: 38965251 PMC: 11224344. DOI: 10.1038/s41598-024-64484-9.

[Notch1/Akt/Foxo1 Pathway Regulated by Kisspeptin Is Involved in Endometrial Decidualization in Patients With Recurrent Spontaneous Abortion].

Yang Y, Zhang J, Li D, Liu C, Guo R, Xiao Y Sichuan Da Xue Xue Bao Yi Xue Ban. 2024; 55(3):542-551.

PMID: 38948287 PMC: 11211770. DOI: 10.12182/20240560206.

Diagnostic utility of clinicodemographic, biochemical and metabolite variables to identify viable pregnancies in a symptomatic cohort during early gestation.

Hill C, Phelan M, Dutton P, Busuulwa P, Maclean A, Davison A Sci Rep. 2024; 14(1):11172.

PMID: 38750192 PMC: 11096363. DOI: 10.1038/s41598-024-61690-3.

Kisspeptin a potential therapeutic target in treatment of both metabolic and reproductive dysfunction.

Sliwowska J, Woods N, Alzahrani A, Paspali E, Tate R, Ferro V J Diabetes. 2024; 16(4):e13541.

PMID: 38599822 PMC: 11006622. DOI: 10.1111/1753-0407.13541.

The kisspeptin system in and beyond reproduction: exploring intricate pathways and potential links between endometriosis and polycystic ovary syndrome.

Salmeri N, Vigano P, Cavoretto P, Marci R, Candiani M Rev Endocr Metab Disord. 2023; 25(2):239-257.

PMID: 37505370 DOI: 10.1007/s11154-023-09826-0.

References

Taran F, Kagan K, Hubner M, Hoopmann M, Wallwiener D, Brucker S . The Diagnosis and Treatment of Ectopic Pregnancy. Dtsch Arztebl Int. 2015; 112(41):693-703. PMC: 4643163. DOI: 10.3238/arztebl.2015.0693. View

Jayasena C, Abbara A, Izzi-Engbeaya C, Comninos A, Harvey R, Gonzalez Maffe J . Reduced levels of plasma kisspeptin during the antenatal booking visit are associated with increased risk of miscarriage. J Clin Endocrinol Metab. 2014; 99(12):E2652-60. PMC: 4255122. DOI: 10.1210/jc.2014-1953. View

Qiao C, Wang C, Shang T, Lin Q . [Clinical significance of KiSS-1 and matrix metalloproteinase-9 expression in trophoblasts of women with preeclampsia and their relation to perinatal outcome of neonates]. Zhonghua Fu Chan Ke Za Zhi. 2005; 40(9):585-90. View

Adali E, Kurdoglu Z, Kurdoglu M, Kamaci M, Kolusari A, Yildizhan R . Metastin levels in pregnancies complicated by pre-eclampsia and their relation with disease severity. J Matern Fetal Neonatal Med. 2012; 25(12):2671-5. DOI: 10.3109/14767058.2012.708369. View

Bowe J, King A, Kinsey-Jones J, Foot V, Li X, OByrne K . Kisspeptin stimulation of insulin secretion: mechanisms of action in mouse islets and rats. Diabetologia. 2009; 52(5):855-62. DOI: 10.1007/s00125-009-1283-1. View

Vikman J, Ahren B . Inhibitory effect of kisspeptins on insulin secretion from isolated mouse islets. Diabetes Obes Metab. 2009; 11 Suppl 4:197-201. DOI: 10.1111/j.1463-1326.2009.01116.x. View

Thame M, Osmond C, Bennett F, Wilks R, Forrester T . Fetal growth is directly related to maternal anthropometry and placental volume. Eur J Clin Nutr. 2004; 58(6):894-900. DOI: 10.1038/sj.ejcn.1601909. View

Madazli R, Bulut B, Tuten A, Aydin B, Demirayak G, Kucur M . First-trimester maternal serum metastin, placental growth factor and chitotriosidase levels in pre-eclampsia. Eur J Obstet Gynecol Reprod Biol. 2012; 164(2):146-9. DOI: 10.1016/j.ejogrb.2012.06.016. View

Seminara S, Messager S, Chatzidaki E, Thresher R, Acierno Jr J, Shagoury J . The GPR54 gene as a regulator of puberty. N Engl J Med. 2003; 349(17):1614-27. DOI: 10.1056/NEJMoa035322. View

10.

Ziyaraa M, Hamdan F, Mousa L . Correlation of Kisspeptin-10 level and fetal well-being in preeclamptic patients. Taiwan J Obstet Gynecol. 2017; 55(6):840-846. DOI: 10.1016/j.tjog.2015.10.028. View

11.

Seymour A, Scott V, Augustine R, Bouwer G, Campbell R, Brown C . Development of an excitatory kisspeptin projection to the oxytocin system in late pregnancy. J Physiol. 2016; 595(3):825-838. PMC: 5285723. DOI: 10.1113/JP273051. View

12.

Williams Z . Inducing tolerance to pregnancy. N Engl J Med. 2012; 367(12):1159-61. PMC: 3644969. DOI: 10.1056/NEJMcibr1207279. View

13.

Yuksel S, Ketenci Gencer F . Serum kisspeptin, to discriminate between ectopic pregnancy, miscarriage and first trimester pregnancy. J Obstet Gynaecol. 2022; 42(6):2095-2099. DOI: 10.1080/01443615.2022.2028747. View

14.

Levine R, Maynard S, Qian C, Lim K, England L, Yu K . Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004; 350(7):672-83. DOI: 10.1056/NEJMoa031884. View

15.

Petrini A, Spandorfer S . Recurrent Ectopic Pregnancy: Current Perspectives. Int J Womens Health. 2020; 12:597-600. PMC: 7414932. DOI: 10.2147/IJWH.S223909. View

16.

Tolson K, Marooki N, Wolfe A, Smith J, Kauffman A . Cre/lox generation of a novel whole-body Kiss1r KO mouse line recapitulates a hypogonadal, obese, and metabolically-impaired phenotype. Mol Cell Endocrinol. 2019; 498:110559. PMC: 6814569. DOI: 10.1016/j.mce.2019.110559. View

17.

Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden J, Le Poul E . The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem. 2001; 276(37):34631-6. DOI: 10.1074/jbc.M104847200. View

18.

Hafner E, Metzenbauer M, Hofinger D, Munkel M, Gassner R, Schuchter K . Placental growth from the first to the second trimester of pregnancy in SGA-foetuses and pre-eclamptic pregnancies compared to normal foetuses. Placenta. 2003; 24(4):336-42. DOI: 10.1053/plac.2002.0918. View

19.

Biscaro A, Braga A, Berkowitz R . Diagnosis, classification and treatment of gestational trophoblastic neoplasia. Rev Bras Ginecol Obstet. 2015; 37(1):42-51. DOI: 10.1590/SO100-720320140005198. View

20.

Buchanan T . Pancreatic B-cell defects in gestational diabetes: implications for the pathogenesis and prevention of type 2 diabetes. J Clin Endocrinol Metab. 2001; 86(3):989-93. DOI: 10.1210/jcem.86.3.7339. View