Kisspeptin: new biomarker of pregnancy
Keywords:Asymptomatic pregnant, Early pregnancy, Gestational age, Hormone, Kisspeptin
Background: The recently identified hormone kisspeptin has been suggested to play an important regulatory role in placentation. The aim and objective of the study is the measurement of serum kisspeptin level in asymptomatic pregnant women and to find out the association of serum kisspeptin with gestational age in women with early pregnancy.
Methods: This was a longitudinal study to the evaluation of 178 asymptomatic pregnant women with a gestation of 6 to 16 weeks attending routine antenatal booking visit recruited as study participants from the Antenatal Clinical of Obstetrics and Gynaecology Department, S.M.S. Medical College and Attached Hospitals, Jaipur, Rajasthan, India.
Results: After initial clinical examination of every participant, a single blood sample was taken for the measurement of serum kisspeptin. Serum kisspeptin measurement test was performed by ELISA method and results were expressed as ng/ml. Pregnancy outcome was recorded prospectively. Mean serum kisspeptin level of study participants was 2.80±1.87ng/ml and median were 2.41 (Range 0.244-14.06ng/ml). Our result showed the relationship of serum kisspeptin with gestational age (GA) (p<0.000).
Conclusions: serum kisspeptin level increases in pregnancy and showed positive relationship with gestational age significantly (p<0.000).
Ohtaki T, Shintani Y, Honda S. Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature. 2001;411:613-7.
Muir AI, Chamberlain L, Elshourbagy NA. AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1. J Biol Chem. 2001;276:28969-75.
West A, Vojta PJ, Welch DR, Weissman BE. Chromosome localization and genomic structure of the KiSS-1 metastasis suppressor gene (KISS1). Genomics. 1998;54:145-8.
Pinilla L, Aguilar E, Dieguez C, Millar RP, Tena-Sempere M. Kisspeptins and reproduction: physiological roles and regulatory mechanisms. Physiol Rev. 2012;92:1235-316.
Hu KL, Zhao H, Chang HM, Yu Y, Qiao J. Kisspeptin/Kisspeptin receptor system in the ovary. Front Endocrinol (Lausanne). 2017;8:365.
Lee YR, Tsunekawa K, Moon MJ, Um HN, Hwang J. Molecular evolution of multiple forms of kisspeptins and GPR54 receptors in vertebrates. Endocrinology. 2009;150:2837-46.
Lee DK, Nguyen T, O’Neill GP, Cheng R, Liu Y, Howard AD, et al. Discovery of a receptor related to the galanin receptors. FEBS Lett. 1999;446:103-7.
Bilban M, Ghaffari-Tabrizi N, Hintermann E. Kisspeptin-10, a KiSS-1/ metastin- derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts. J Cell Sci. 2004;117:1319-28.
Roseweir AK, Katz AA, Millar RP. Kisspeptin-10 inhibits cell migration in vitro via a receptor-GSK3β-FAK feedback loop in HTR8SVneo cells. Placenta. 2012;33:408-15.
Kotani M, Detheux M, Vandenbogaerde A. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem. 2001;276:34631-6.
Norwitz ER, Schust DJ, Fisher SJ. Implantation and the survival of early pregnancy. N Engl J Med. 2001;345:1400-8.
Xu X, Chiung YM, Lu F, Qiu S, Ji M, Huo X. Associations of cadmium, bisphenol A and polychlorinated biphenyl co-exposure in utero with placental gene expression and neonatal outcomes. Reprod Toxicol. 2015;52:62-70.
Sullivan-Pyke C, Haisenleder DJ, Senapati S, Nicolais O, Eisenberg E, Sammel MD, et al. Kisspeptin as a new serum biomarker to discriminate miscarriage from viable intrauterine pregnancy. Fertil Steril. 2018;109:137-41.e132.
Horikoshi Y, Matsumoto H, Takatsu Y, Ohtaki T, Kitada C, Usuki S, et al. Dramatic elevation of plasma metastin concentrations in human pregnancy: metastin as a novel placenta-derived hormone in humans. J Clin Endocrinol Metab. 2003;88:914-9.
Jayasena CN, Abbara A, Izzi-Engbeaya A, Comninos AN. 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-E2660.
Babwah AV. Uterine and placental KISS1 regulate pregnancy: what we know and the challenges that lie ahead. Reproduction. 2015;150:R121-R128.
Savitz DA, Hertz-PicciottoI, Poole C, Olshan AF. Epidemiologic measures of the course and outcome of pregnancy. Epidemiol Rev. 2002;24:91-101.
Newbatt E, Beckles Z, Ullman R, Lumsden MA. Ectopic pregnancy and miscarriage: summary of NICE guidance. BMJ. 2012;345:e8136.
Pillai RN, Konje JC, Tincello DG, Potdar N. Role of serum biomarkers in the prediction of outcome in women with threatened miscarriage: a systematic review and diagnostic accuracy meta-analysis. Hum Reprod Update. 2016;22:228-39.
Dhillo WS, Savage P, Murphy KG, Chaudhri OB, Patterson M, Nijher GM, et al. Plasma kisspeptin is raised in patients with gestational trophoblastic neoplasia and falls during treatment. Am J Physiol Endocrinol Metabol. 2006;291:E878-E884.