The Role of Kisspeptin in the Pathogenesis of Pregnancy Complications: A Narrative Review
Abstract
:1. Introduction
2. Scope and Methodology
3. The KISS-1 Gene, Kisspeptin and Its Signaling
4. Kisspeptin Level throughout Pregnancy
5. Role of Kisspeptin in Gestational Diabetes Mellitus—A Placenta-Pancreas Crosstalk
6. Role of Kisspeptin in the Pathogenesis of Disorders from the Spectrum of Impaired Implantation and Placentation
6.1. Implantation and Kisspeptin-Induced Miscarriages
6.2. Kisspeptin in Placentation and Pathophysiology of Placental Diseases
6.2.1. Kisspeptin and Preeclampsia
6.2.2. Kisspeptin and Fetal Growth Restriction
7. Kisspeptin and Neonatal Outcomes
8. Conclusions and Future Perspectives
Disorder | KISS Derivatives | Ethnicity (Country) | Sample Type | Trimester of Pregnancy | Model (Number) of the Study Groups | Description of Findings | Authors |
---|---|---|---|---|---|---|---|
KISS | Mixed (White, Black, Asian, Other) | plasma | All trimester | PE (20): mild (7), severe (13) PIH (12) CG (265) | ↑ KISS level in HDP women vs. CG The rate of rise in KISS with gestation ↑ in pregnancies affected by HDP than in CG OR of HDP increased by 30% (95% CI, 16–47%; p < 0.0001) for every 1 nmol/L increase in plasma kisspeptin | Abbara et al., 2022 [11] | |
KISS-1 | Asian (Turkey) | plasma | <34. hbd ≥34. hbd | early-onset PE (20) vs. CG (20) late-onset PE (45) vs. CG (40) | No difference ↑ level of KISS-1 in late-onset PE vs. CG | Ibanoglu et al., 2022 [121] | |
KISS-1 | Asian (China) | serum | Second Third | PE women (25) CG (25) | ↑ levels of KISS-1 and TGF-β1 in PE women vs. CG | Fang et al., 2022 [48] | |
KISS-1 | Asian (China) | human trophoblast cell line placenta serum | Second Third | PE women (17) CG (16) | EGF downregulated KISS-1 by activating EGFR-mediated PI3K/AKT signaling pathway ↓ EGF and ↑ KISS-1 level in PE women vs. CG | Fang et al., 2021 [111] | |
KISS-10 | Asian (Jordan) | plasma | Second Third | PE women (60) CG (40) | ↓ KISS-10 level in PE women vs. CG KISS-10 levels correlate positively with β-hCG and negatively with LH, and FSH in PE women in the third trimester | Al-Kaabi et al., 2020 [112] | |
KISS-10 | Asian (Iraq) | plasma | Second Third | PE women (60) Mild form (39) Severe form (21) CG (40) | ↓ KISS-10 level in PE vs. CG ↓ KISS-10 level in severe PE vs. mild one ↓ KISS-10 level in severe PE during the second trimester vs. the third one | Ziyaraa et al., 2016 [114] | |
KISS-10 GPR-54 | European (UK) | placenta serum (maternal, umbilical cord blood | Third | PE women (19) CG (30) | ↑ KISS expression in PE placenta vs. CG No differences in KISS-1 and GPR-54 mRNA expressions in placentas ↓ KISS-10 level in serum in SG vs. CG No significant distinctions in KISS-10 levels in cord blood between SG and CG | Matjila et al., 2016 [116] | |
KISS-1KISS-1R | European (UK) | placenta | First Third | First trimester (10) PE women at delivery (10) CG (10) | ↓ KISS-1 and KISS-1R expression between early and term pregnancy PE vs. normal pregnancy placental samples: ↓ KISS-1 expression and ↑ expression of KISS-1R | Cartwright et al., 2012 [55] | |
KISS | European (UK) | plasma | 16. hbd 28. hbd 36. hbd | Obese women with PE (11) Uncomplicated pregnancy in obese women (158) Lean pregnant women—CG (48) | Maternal KISS levels ↑ during pregnancy ↓ KISS level in obese women with PE at 16. hbd compared to obese pregnant women without PE and CG Optimal cut-off concentration of KISS at 16. hbd to predict PE—596 pmol/L (sensitivity: 85.7%; specificity: 71.4%) | Logie et al., 2012 [127] | |
KISS-1 GPR-54 | Asian (China) | placenta | 23+0–33+6. hbd 34+0–39+0. hbd | early-onset PE (36) vs. CG (40) late-onset PE (40) vs. CG (40) | ↑ KISS-1 mRNA expression in early-onset SG vs. CG No differences in KISS-1 mRNA expression in late-onset PE No differences in GPR-54 expression | Qiao et al., 2012 [118] | |
KISS-54 | Asian (Turkey) | serum | First | Women who developed PE (31) CG (30) | ↓ KISS-54 level in SG vs. CG (AUC: 0.797 to predict PE) | Madazli et al., 2012 [115] | |
KISS-54 | Asian (Turkey) | plasma | Third | Mild PE (15) Severe PE (24) CG (50) | ↓ KISS-54 level in PE vs. CG No differences between mild and severe PE | Adali et al., 2012 [113] | |
KISS-54 KISS-14 KISS-10 | European (Serbia) | plasma | Second Third | PE (28) GH (18) CG (25) | ↓ KISS-54 level in PE vs. CG No differences in KISS level between GH and CG | Cetković et al., 2012 [68] | |
KISS-1 | Asian (China) | placenta human trophoblast cell line | Third | PE women (47) CG (30) Human trophoblast cell line transfected (SG) and non-transfected one (CG) with KISS-1 vector | ↑ KISS-1 mRNA and protein expression in PE women vs. CG ↓ MMP-9, MMP-2 mRNA, and protein expression in PE vs. CG No differences in cell proliferation between SG and CG ↓ invasion ability in SG compared to CG | Zhang et al., 2011 [119] | |
KISS-1 | Amerindian (Mexico) | placenta | Third | PE women (27) CG (27) | ↑ KISS-1 expression in SG vs. CG | Vazquez-Alaniz et al., 2011 [120] | |
KISS-54 | European (UK) | plasma | Third | PE women (8) PIH (19) CG (78) | No differences | Nijher et al., 2010 [136] | |
KISS-54 | European (UK) | serum | Second | PE women (57) CG (317) | ↓ KISS-54 level in PE individuals vs. CG | Armstrong et al., 2009 [117] | |
KISS-1 | European (Italy) | whole blood | Third | PE (6) CG (30) | ↓ KISS-1 mRNA expression in PE vs. CG | Farina et al., 2006 [137] | |
Fetal Growth Restriction | KISS | Mixed (White, Black, Asian, Other) | plasma | All trimester | FGR or SGA (17) CG (265) | ↓ KISS level in FGR vs. CG (especially in the late first and third trimester) Lower increase in KISS level during gestation in FGR vs. CG KISS in diagnosis FGR: OR 0.72 (0.54–0.96), p = 0.025 | Abbara et al., 2022 [11] |
KISS-10 | Asian (Iraq) | plasma | Second Third | PE women (60) Mild form (39) Severe form (21) CG (40) | Positive correlation between KISS level in the third trimester and EFW (r = 0.395, p = 0.012) in CG, and in the second (r = 0.760, p = 0.001), third (r = 0.920, p = 0.0001) trimesters in severe PE Negative correlation between KISS level in the third trimester and FBW in CG (r = −0.410, p = 0.009) | Ziyaraa et al., 2016 [114] | |
KISS-1 | Mixed (Australia) | Whole blood (maternal) | 26–30 hbd | Late-onset FGR (40) CG (80) | ↑ KISS-1 expression in FGR vs. CG AUC for KISS01 as a discriminative marker for FGR: 0.64, p = 0.01 (FGR: 0.19 (0.08–0.81) vs. CG: 0.96 (0.13–2.85) | Whitehead et al., 2016 [138] | |
KISS-1 KISS-1R | Animal model (rat) | Placenta | 16. and 22. day of gestation | Dexamethasone-induced FGR (6) CG (6) | ↑ KISS-1 mRNA expression in FGR vs. CG ↑ KISS-1R mRNA expression in 16. day of gestation and ↓ in 22. day of gestation in FGR vs. CG | Mark et al., 2013 [139] | |
KISS-54 KISS-14 KISS-10 | European (Serbia) | plasma | Second Third | PE (28) GH (18) CG (25) | No correlation between KISS-54, placental, and birth weight at delivery in all groups | Cetković et al., 2012 [68] | |
KISS | European (UK) | plasma | 16. hbd 28. hbd 36. hbd | Obese women with PE (11) Uncomplicated pregnancy in obese women (158) Lean pregnant women—CG (48) | Lower KISS levels at 16. hbd were associated with lower birth weight (r = 0.16, p = 0.06) | Logie et al., 2012 [127] | |
KISS-1 | Mixed (Australia) | Whole blood Placenta | Third (<34. hbd) | FGR (20) Preterm Birth (15—blood samples, 8—placenta) Term Birth (8—placenta) | ↑ KISS-1 RNA expression in maternal blood in FGR vs. women with preterm delivery ↑ KISS-1 RNA expression in the placenta in FGR vs. women with preterm and term delivery | Whitehead et al., 2012 [140] | |
KISS-10 | Asian (Turkey) | Plasma | First | Women with early pregnancy bleeding (20) CG (20) | ↓ KISS-10 level in the first trimester in SG and was associated with an increased risk of IUGR (10% vs. 0%) | Kavvasoglu et al., 2012 [83] | |
KISS-54 | European (UK) | Serum | Second | FGR (118) CG (317) | ↓ KISS-54 level in FGR vs. CG | Armstrong et al., 2009 [117] | |
KISS-54 | European (Netherlands) | Plasma | 8–14 hbd. | SGA (31) CG (31) | ↓ KISS-54 level in SGA vs. CG | Smets et al., 2008 [128] |
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Szydełko-Gorzkowicz, M.; Poniedziałek-Czajkowska, E.; Mierzyński, R.; Sotowski, M.; Leszczyńska-Gorzelak, B. The Role of Kisspeptin in the Pathogenesis of Pregnancy Complications: A Narrative Review. Int. J. Mol. Sci. 2022, 23, 6611. https://doi.org/10.3390/ijms23126611
Szydełko-Gorzkowicz M, Poniedziałek-Czajkowska E, Mierzyński R, Sotowski M, Leszczyńska-Gorzelak B. The Role of Kisspeptin in the Pathogenesis of Pregnancy Complications: A Narrative Review. International Journal of Molecular Sciences. 2022; 23(12):6611. https://doi.org/10.3390/ijms23126611
Chicago/Turabian StyleSzydełko-Gorzkowicz, Magdalena, Elżbieta Poniedziałek-Czajkowska, Radzisław Mierzyński, Maciej Sotowski, and Bożena Leszczyńska-Gorzelak. 2022. "The Role of Kisspeptin in the Pathogenesis of Pregnancy Complications: A Narrative Review" International Journal of Molecular Sciences 23, no. 12: 6611. https://doi.org/10.3390/ijms23126611