Changes in Circulating Kisspeptin Levels During Each Trimester in Women With Antenatal Complications.
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ABSTRACT: Context
Antenatal complications such as hypertensive disorders of pregnancy (HDP), fetal growth restriction (FGR), gestational diabetes (GDM), and preterm birth (PTB) are associated with placental dysfunction. Kisspeptin has emerged as a putative marker of placental function, but limited data exist describing circulating kisspeptin levels across all 3 trimesters in women with antenatal complications.Objective
We aimed to assess whether kisspeptin levels are altered in women with antenatal complications.Methods
Women with antenatal complications (n = 105) and those with uncomplicated pregnancies (n = 265) underwent serial ultrasound scans and blood sampling at the Early Pregnancy Assessment Unit at Hammersmith Hospital, UK, at least once during each trimester (March 2014 to March 2017). The women with antenatal complications (HDP [n = 32], FGR [n = 17], GDM [n = 35], PTB [n = 11], and multiple complications [n=10]) provided 373 blood samples and the controls provided 930 samples. Differences in circulating kisspeptin levels were assessed.Results
Third-trimester kisspeptin levels were higher than controls in HDP but lower in FGR. The odds of HDP adjusted for gestational age, maternal age, ethnicity, BMI, smoking, and parity were increased by 30% (95% CI, 16%-47%; P < 0.0001), and of FGR were reduced by 28% (95% CI, 4-46%; P = 0.025), for every 1 nmol/L increase in plasma kisspeptin. Multiple of gestation-specific median values of kisspeptin were higher in pregnancies affected by PTB (P = 0.014) and lower in those with GDM (P = 0.020), but not significantly on multivariable analysis.Conclusion
We delineate changes in circulating kisspeptin levels at different trimesters and evaluate the potential of kisspeptin as a biomarker for antenatal complications.
SUBMITTER: Abbara A
PROVIDER: S-EPMC8684464 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The kiss system is known to regulate puberty and to be involved in the onset of reproduction, acting upstream of the Brain-Pituitary-Gonad axis in gonadotrophin releasing hormone neurons and stimulating secretion of GnRH. Kisspeptin has been proven to be a novel therapeutic for fertility disorders in humans. In fish, positive results have also observed the prospective of this hormone to induce gamete development. During the last two decades, support has been obtained describing the key role of microRNAs (miRNA) in regulating gene expression at the post-transcriptional level and they have been recommended as relevant biomarkers in reproductive studies. Senegalese sole is a marine flatfish species with high importance in the European aquaculture industry, due to its good growth rate and high market value. However, this species presents a bottleneck in terms of reproduction, which does not allow to close the cycle in captive conditions. Hence, this study aimed to observe the effect of a novel hormonal treatment using kisspeptin in miRNA expression related to reproductive performance in cultured Senegalese sole breeders. For this purpose, Senegalese sole F1 broodstock were held at CCMAR facilities in 4 tanks of 3m3 (n = 12/per tank, sex ratio 1:1) under natural photoperiod and temperature conditions. During the reproductive season, the animals from each 2 of the tanks were treated either with SSkiss2_v2 decapeptide in a single intramuscular injection, or with a PBS injection for control groups. After the treatment (2 and 4 days), all fish were anesthetized and sampled for blood collection. Afterwards, plasma was obtained to determine several parameters related to reproductive physiology (Fsh, Lh and sexual esteroids (T, 11-KT and E2)) and miRNAs regulation. After observing the high implication of this treatment in the gonadotrofins, above all in Fsh and sexual esteroids, above all in T, the RNA was extracted from blood plasma using miRNeasy Serum/Plasma Kit (Qiagen, Germany) and libraries were prepared using NEXTflex Small RNA-Seq kit v3 (Bioo Scientific, USA). Small RNA sequencing (sRNA-seq) (NextSeq 500) was performed on sole treated with kisspeptin (n = 16) and non-treated control fish (n = 14). A total of 1,467 unique miRNAs were expressed in Senegalese sole plasma. A multidimensional scaling (MDS) plot showed no clear clustering of the samples with the kisspeptin treatment. However, the differential expression analysis revealed one miRNA, miR-1-3p, to be highly up-regulated in both males and females treated with kisspeptin compared to control sole. This miRNA is linked with myogenesis and angiogenesis, and skeletal muscle development in fish. Three isomirs (let 7e, miR-199a-3p, miR-100-5p) were differentially expressed between females treated and control fish. MicroRNA let-7e is an important regulator of endothelial function and inflammation, related to testosterone pathway release; miR-199a-3p plays an important role in inflammation and women fertility and miR-100-5p might be implicated in the regulation of cell growth and oocytes maturation. In conclusion, kisspeptin treatment may affect gonad maturation in females and muscle growth in males. Our data support the possibility of using circulating miRNAs as less invasive physiological biomarkers in fish reproduction.
2020-12-16 | GSE153469 | GEO
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Project description:ObjectiveTo compare the performance of kisspeptin and beta human chorionic gonadotropin (βhCG), both alone and in combination, as biomarkers for miscarriage throughout the first trimester.DesignProspective, nested case-control study.SettingTertiary Centre, Queen Charlotte Hospital, London, United Kingdom.Patient(s)Adult women who had miscarriages (n = 95, 173 samples) and women with healthy pregnancies (n = 265, 557 samples).Intervention(s)The participants underwent serial ultrasound scans and blood sampling for measurement of plasma kisspeptin and βhCG levels during the first trimester.Main outcome measure(s)The ability of plasma kisspeptin and βhCG levels to distinguish pregnancies complicated by miscarriage from healthy pregnancies unaffected by miscarriage.Result(s)Gestation-adjusted levels of circulating kisspeptin and βhCG were lower in samples from women with miscarriages than in women with healthy pregnancies by 79% and 70%, respectively. The area under the receiver-operating characteristic curve for identifying miscarriage during the first trimester was 0.874 (95% confidence interval [CI] 0.844-0.904) for kisspeptin, 0.859 (95% CI 0.820-0.899) for βhCG, and 0.916 (95% CI 0.886-0.946) for the sum of the two markers. The performance of kisspeptin in identifying miscarriage improved with increasing length of gestation, whereas that of βhCG worsened. A decision matrix incorporating kisspeptin, βhCG, and gestational age had 83% to 87% accuracy for the prediction of miscarriage.Conclusion(s)Plasma kisspeptin is a promising biomarker for miscarriage and provides additional value to βhCG alone, especially during later gestational weeks of the first trimester.
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