Souvislost mezi hladinou kisspeptinu v séru v I. trimestru a prenatálními komplikacemi

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Autoři: Özlem Kayacık Günday ¹ ; Ayhan Vurmaz ² ; Mehmet Yılmazer ¹
Působiště autorů: Department of Obstetrics and Gynecology, Faculty of Medicine, Afyonkarahisar University of Health Sciences Afyonkarahisar, Turkey ¹; Department of Biochemistry, Faculty of Medicine, Afyonkarahisar University of Health Sciences, Afyonkarahisar, Turkey ²
Vyšlo v časopise: Ceska Gynekol 2025; 90(3): 212-221
Kategorie: Původní práce
doi: https://doi.org/10.48095/cccg2025212

Souhrn

Cíl: Naším cílem bylo zhodnotit využitelnost hladiny kisspeptinu (KP) v séru, měřeného v I. trimestru (11–14 týdnu), jako nového biomarkeru, který může predikovat prenatální komplikace. Materiály a metody: Prospektivní případová kontrolní studie prospektivně shromážděných dat. Vzorky krve všech pacientek (n = 124) byly uchovány při –70 °C pro stanovení hladin KP-10 a KP-54 v séru. Byly stanoveny a srovnány hladiny KP u žen, u kterých došlo ke komplikacím vč. retardace růstu plodu (FGR –⁠ fetal growth retardation), těhotenstvím indukované hypertenze (PIH –⁠ pregnancy-induced hypertension), předčasného porodu, gestačního diabetu a úmrtí plodu. Kontrolní skupinu tvořily odpovídající subjekty, které dokončily těhotenství bez problémů. Byl zkoumán prediktivní účinek hladiny KP v séru na nepříznivé výsledky těhotenství. Výsledky: Mezi všemi pacientkami s nepříznivými výsledky těhotenství byla hladina KP-10 významně vyšší u těch, u kterých došlo k FGR (p = 0,025). V kohortě pacientek postižených těhotenstvím indukovanou hypertenzí (PIH), buď samotnou nebo doprovázenou preeklampsií, byla zaznamenána tendence k vyšším hladinám KP-10 (p = 0,059), ačkoli nebylo dosaženo statistické významnosti. Nicméně pokud jde o KP-10, vypočtená cutoff hodnota a plocha pod křivkou (AUC –⁠ area under the curve) pro predikci nástupu FGR byly statisticky významné (AUC: 0,684; p = 0,006). Bylo zjištěno, že model vytvořený s KP-10, PIH a plazmatickým proteinem A spojeným s těhotenstvím (PAPP-A) je významný při predikci vývoje FGR (p = 0,006; NPV: 98 %; PPV: 21,4 %; OR: 0,10; 95% CI 0,016–0,611). Závěry: Hladiny KP v séru matky v I. trimestru mohou být využity jako biomarker v I. trimestru, který může predikovat vývoj FGR.

Klíčová slova:

kisspeptin-10 – kisspeptin-54 – výsledek těhotenství – omezení růstu plodu – těhotenstvím indukovaná hypertenze

Zdroje

1. Lee JH, Miele ME, Hicks DJ et al. KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst 1996; 88 (23): 1731–1737. doi: 10.1093/jnci/88.23.1731.

2. Kotani M, Detheux M, Vandenbogaerde A et al. 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): 34631–34636. doi: 10.1074/jbc.M104847200.

3. Horikoshi Y, Matsumoto H, Takatsu Y 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 (2): 914–919. doi: 10.1210/jc.2002-021235.

4. Abbara A, Al-Memar M, Phylactou M et al. Performance of plasma kisspeptin as a biomarker for miscarriage improves with gestational age during the first trimester. Fertil Steril 2021; 116 (3): 809–819. doi: 10.1016/j.fertnstert.2021. 04.031.

5. Bilban M, Ghaffari-Tabrizi N, Hintermann E et al. Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts. J Cell Sci 2004; 117 (Pt 8): 1319–1328. doi: 10.1242/jcs.00971.

6. Hiden U, Bilban M, Knöfler M et al. Kisspeptins and the placenta: regulation of trophoblast invasion. Rev Endocr Metab Disord 2007; 8 (1): 31–39. doi: 10.1007/s11154-007-9030-8.

7. Hu KL, Chang HM, Zhao HC et al. Potential roles for the kisspeptin/kisspeptin receptor system in implantation and placentation. Hum Reprod Update 2019; 25 (3): 326–343. doi: 10.1093/humupd/dmy046.

8. Wu S, Zhang H, Tian J et al. Expression of kisspeptin/GPR54 and PIBF/PR in the first trimester trophoblast and decidua of women with recurrent spontaneous abortion. Pathol Res Pract 2014; 210 (1): 47–54. doi: 10.1016/j.prp.2013.09.017.

9. Tsoutsouki J, Patel B, Comninos AN et al. Kisspeptin in the prediction of pregnancy complications. Front Endocrinol (Lausanne) 2022; 13 : 942664. doi: 10.3389/fendo.2022.942664.

10. Abbara A, Al-Memar M, Phylactou M et al. Changes in circulating kisspeptin levels during each trimester in women with antenatal complications. J Clin Endocrinol Metab 2022; 107 (1): e71–e83. doi: 10.1210/clinem/dgab617.

11. Kapustin RV, Drobintseva AO, Alekseenkova EN et al. Placental protein expression of kisspeptin-1 (KISS1) and the kisspeptin-1 receptor (KISS1R) in pregnancy complicated by diabetes mellitus or preeclampsia. Arch Gynecol Obstet 2020; 301 (2): 437–445. doi: 10.1007/s00404-019-05408-1.

12. Torricelli M, Galleri L, Voltolini C et al. Changes of placental Kiss-1 mRNA expression and maternal/cord kisspeptin levels at preterm delivery. Reprod Sci 2008; 15 (8): 779–784. doi: 10.1177/1933719108322442.

13. Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol 2020; 135 (6): e237–e260. doi: 10.1097/AOG.0000000000003891.

14. Aneman I, Pienaar D, Suvakov S et al. Mechanisms of key innate immune cells in early -⁠ and late-onset preeclampsia. Front Immunol 2020; 11 : 1864. doi: 10.3389/fimmu.2020.01864.

15. Unterscheider J, Daly S, Geary MP et al. Optimizing the definition of intrauterine growth restriction: the multicenter prospective PORTO Study. Am J Obstet Gynecol 2013; 208 (4): 290.e1–290.e6. doi: 10.1016/j.ajog.2013.02.007.

16. Tucker J, McGuire W. Epidemiology of preterm birth. BMJ 2004; 329 (7467): 675–678. doi: 10.1136/bmj.329.7467.675.

17. Jacklin PB, Maresh MJ, Patterson CC et al. A cost-effectiveness comparison of the NICE 2015 and WHO 2013 diagnostic criteria for women with gestational diabetes with and without risk factors. BMJ Open 2017; 7 (8): e016621. doi: 10.1136/bmjopen-2017-016621.

18. Armstrong RA, Reynolds RM, Leask R et al. Decreased serum levels of kisspeptin in early pregnancy are associated with intra-uterine growth restriction and pre-eclampsia. Prenat Diagn 2009; 29 (10): 982–985. doi: 10.1002/pd.2328.

19. Hafner E, Metzenbauer M, Höfinger D et al. 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): 336–342. doi: 10.1053/plac.2002.0918.

20. Ibanoglu MC, Oskovi-Kaplan ZA, Kara O et al. Relationship between kisspeptin levels in the third trimester and late-onset fetal growth restriction: a case-control study. Placenta 2023; 140 : 1–5. doi: 10.1016/j.placenta.2023.07.012.

21. Mureșan D, Rotar IC, Stamatian F. The usefulness of fetal Doppler evaluation in early versus late onset intrauterine growth restriction. Review of the literature. Med Ultrason 2016; 18 (1): 103–109. doi: 10.11152/mu.2013.2066. 181.dop.

22. Ali A, Hadlich F, Abbas MW et al. MicroRNA -⁠ -mRNA networks in pregnancy complications: a comprehensive downstream analysis of potential biomarkers. Int J Mol Sci 2021; 22 (5): 2313. doi: 10.3390/ijms22052313.

23. Foidart JM, Schaaps JP, Chantraine F et al. Dysregulation of anti-angiogenic agents (sFlt-1, PLGF, and sEndoglin) in preeclampsia –⁠ a step forward but not the definitive answer. J Reprod Immunol 2009; 82 (2): 106–111. doi: 10.1016/j.jri.2009.09.001.

24. Conde-Agudelo A, Villar J, Lindheimer M. World Health Organization systematic review of screening tests for preeclampsia. Obstet Gynecol 2004; 104 (6): 1367–1391. doi: 10.1097/01.AOG.0000147599.47713.5d.

25. Madazli R, Bulut B, Tuten A et al. First-trimester maternal serum metastin, placental growth factor and chitotriosidase levels in pre-eclampsia. Eur J Obstet Gynecol Reprod Biol 2012; 164 (2): 146–149. doi: 10.1016/j.ejogrb.2012.06.016.

26. Fang L, Yan Y, Gao Y et al. TGF-b1 inhibits human trophoblast cell invasion by upregulating kisspeptin expression through ERK1/2 but not SMAD signaling pathway. Reprod Biol Endocrinol 2022; 20 (1): 22. doi: 10.1186/s12958-022-00902-9.

27. Fang L, Gao Y, Wang Z et al. EGF stimulates human trophoblast cell invasion by downregulating ID3-mediated KISS1 expression. Cell Commun Signal 2021; 19 (1): 101. doi: 10.1186/s12964-021-00783-2

28. Ibanoglu MC, Oskovi-Kaplan ZA, Ozgu -⁠ -Erdinc AS et al. Comparison of the Kisspeptin levels in early onset preeclampsia and late-onset preeclampsia. Arch Gynecol Obstet 2022; 306 (4): 991–996. doi: 10.1007/s00404-021 -⁠ 06359-2.

29. Nijher GM, Chaudhri OB, Ramachandran R et al. The effects of kisspeptin-54 on blood pressure in humans and plasma kisspeptin concentrations in hypertensive diseases of pregnancy. Br J Clin Pharmacol 2010; 70 (5): 674–681. doi: 10.1111/j.1365-2125.2010. 03746.x.

30. Raymond D, Peterson E. A critical review of early-onset and late-onset preeclampsia. Obstet Gynecol Surv 2011; 66 (8): 497–506. doi: 10.1097/OGX.0b013e3182331028.

31. de Pedro MA, Morán J, Díaz I et al. Circadian Kisspeptin expression in human term placenta. Placenta 2015; 36 (11): 1337–1339. doi: 10.1016/j.placenta.2015.09.009.

32. Yu Z, Kastenmüller G, He Y et al. Differences between human plasma and serum metabolite profiles. PLoS One 2011; 6 (7): e21230. doi: 10.1371/journal.pone.0021230.

33. Braunthal S, Brateanu A. Hypertension in pregnancy: pathophysiology and treatment. SAGE Open Med 2019; 7 : 2050312119843700. doi: 10.1177/2050312119843700.

34. Wang PH, Yeh CC, Chen YJ et al. Maternal serum markers and preeclampsia. Taiwan J Obstet Gynecol 2015; 54 (4): 339–340. doi: 10.1016/j.tjog.2015.06.001.

35. Maguire JJ, Kirby HR, Mead EJ et al. Inotropic action of the puberty hormone kisspeptin in rat, mouse and human: cardiovascular distribution and characteristics of the kisspeptin receptor. PLoS One 2011; 6 (11): e27601. doi: 10.1371/journal.pone.0027601.

36. Sato K, Shirai R, Hontani M et al. Potent vasoconstrictor Kisspeptin-10 induces atherosclerotic plaque progression and instability: reversal by its receptor GPR54 antagonist. J Am Heart Assoc 2017; 6 (4): e005790. doi: 10.1161/JAHA.117.005790.

37. Cetković A, Miljic D, Ljubić A et al. Plasma kisspeptin levels in pregnancies with diabetes and hypertensive disease as a potential marker of placental dysfunction and adverse perinatal outcome. Endocr Res 2012; 37 (2): 78–88. doi: 10.3109/07435800.2011. 639319.

38. Arslan E, Görkem Ü, Toğrul C. Is there an association between kisspeptin levels and gestational diabetes mellitus? Gynecol Obstet Reprod Med 2020; 26 (3): 179–183. doi: 10.21613/GORM.2019.946.

39. Qiao C, Wang C, Zhao J et al. Elevated expression of KiSS-1 in placenta of Chinese women with early-onset preeclampsia. PLoS One 2012; 7 (11): e48937. doi: 10.1371/journal.pone.0048937.

40. Gomes VC, Sones JL. From inhibition of trophoblast cell invasion to proapoptosis: what are the potential roles of kisspeptins in preeclampsia? Am J Physiol Regul Integr Comp Physiol 2021; 321 (1): R41–R48. doi: 10.1152/ajpregu.00258.2020.

ORCID of authors

Ö. K. Günday 0000-0002-9249-679X

A. Vurmaz 0000-0002-1840-2900

M. Yılmazer 0000-0001-5445-6159

Submitted/Doručeno: 31. 10. 2024

Accepted/Přijato: 6. 1. 2025

Özlem Kayacık Günday, MD

Department of Obstetrics and Gynecology

Afyonkarahisar Health Sciences University

Zafer Sağlık Külliyesi

Dörtyol Mahallesi 2078 Sokak No: 3

Afyonkarahisar