Performance of plasma kisspeptin as a biomarker for miscarriage improves with gestational age during the first trimester

Abbara, Ali; Al‐Memar, M.; Phylactou, Maria; Kyriacou, C.; Eng, Pei Chia; Nadir, Rans; Izzi‐Engbeaya, Chioma; Clarke, Sophie; Mills, Edouard; Daniels, Elisabeth; Huo, Lechun; Pacuszka, Ewa; Yang, Lisa; Patel, Bijal; Tan, Tricia; Bech, Paul; Comninos, Alexander N; Fourie, H.; Kelsey, Tom; Bourne, Tom; Dhillo, Waljit

doi:10.1016/j.fertnstert.2021.04.031

Cited by 17 publications

(16 citation statements)

References 56 publications

(79 reference statements)

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“…Expression of kisspeptin and its receptor is high during early pregnancy and declines as the placenta matures, thus highlighting kisspeptin’s role in placentation ( 14 ). Interestingly, circulating kisspeptin levels increase linearly with advancing gestation and kisspeptin-54 immunoreactivity dramatically rises from 1230 pmol/L during the first trimester to 9590 pmol/L during the third trimester and returns to non-pregnant levels (<100 pmol/L) soon after birth (8 pmol/L) ( 6 , 7 , 20 ).…”

Section: Kisspeptin In Healthy Pregnancymentioning

confidence: 99%

Section: Kisspeptin In Healthy Pregnancymentioning

confidence: 99%

“…Circulating kisspeptin levels are affected by several variables in healthy pregnancy ( 20 ). Whilst gestational and maternal age are associated with raised kisspeptin levels, Afro-Caribbean ethnicity, smoking during pregnancy, and high body mass index (BMI) are associated with reduced kisspeptin levels ( 20 ). Additionally, kisspeptin levels have been shown to be lower in serum compared to plasma samples, and are influenced by pre-analytical factors such as collection tube type, processing time and time to sample storage ( 49 ).…”

Section: Kisspeptin In Healthy Pregnancymentioning

confidence: 99%

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Kisspeptin in the Prediction of Pregnancy Complications

et al. 2022

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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).

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Section: Kisspeptin In Healthy Pregnancymentioning

confidence: 99%

Section: Kisspeptin In Healthy Pregnancymentioning

confidence: 99%

Section: Kisspeptin In Healthy Pregnancymentioning

confidence: 99%

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Kisspeptin in the Prediction of Pregnancy Complications

et al. 2022

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“…Plasma and serum samples were collected as per the assay manufacturer’s guidelines and were stored at –20°C until analysis. Plasma kisspeptin levels were measured using an established manual radioimmunoassay (RRID:AB_2905628, https://scicrunch.org/resources/Any/search?q=AB_2905628&l=AB_2905628 ) ( 15 ), with intra- and interassay coefficients of variation of 8.2% and 10.2%, respectively ( 39 ). LH (RRID:AB_2813909, https://scicrunch.org/resources/Any/search?q=AB_2813909&l=AB_2813909 ), FSH (RRID:AB_2813910, https://scicrunch.org/resources/Any/search?q=AB_2813910&l=AB_2813910 ), and testosterone (RRID:AB_2848165, https://scicrunch.org/resources/Any/search?q=AB_2848165&l=AB_2848165 ) levels were analyzed using automated chemiluminescent immunoassays (Abbott Diagnostics).…”

Section: Methodsmentioning

confidence: 99%

Acute Effects of Kisspeptin Administration on Bone Metabolism in Healthy Men

Comninos

Hansen

Courtney

et al. 2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Osteoporosis results from disturbances in bone formation and resorption. Recent non-human data suggests that the reproductive hormone, kisspeptin, directly stimulates osteoblast differentiation in vitro and thus could have clinical therapeutic potential. However, the effects of kisspeptin on human bone metabolism are currently unknown. Objective To assess the effects of kisspeptin on human bone metabolism in vitro and in vivo. Design In vitro study: Mono- and co-cultures of human osteoblasts and osteoclasts treated with kisspeptin. Clinical study: Randomized, placebo-controlled, double-blind, two-way crossover clinical study in twenty-six men investigating the effects of acute kisspeptin administration (90 minutes) on human bone metabolism, with blood sampling every 30 minutes to +90 minutes. Participants In vitro study: Twelve male blood donors and eight patients undergoing hip replacement surgery. Clinical Study: Twenty-six healthy eugonadal men (age 26.8±5.8 years). Intervention Kisspeptin (versus placebo). Main Outcome Measures Changes in bone parameters and turnover markers. Results Incubation with kisspeptin in vitro increased alkaline phosphatase levels in human bone marrow mesenchymal stem cells by 41.1% (P=0.0022), and robustly inhibited osteoclastic resorptive activity by up to 53.4% (P<0.0001), in a dose-dependent manner. Kisspeptin administration to healthy men increased osteoblast activity, as evidenced by a 20.3% maximal increase in total osteocalcin (P=0.021) and 24.3% maximal increase in carboxylated osteocalcin levels (P=0.014). Conclusions Collectively, these data provide the first human evidence that kisspeptin promotes osteogenic differentiation of osteoblast progenitors and inhibits bone resorption in vitro. Furthermore, kisspeptin acutely increases the bone formation marker osteocalcin but not resorption markers in healthy men, independent of downstream sex-steroid levels. Kisspeptin could therefore have clinical therapeutic application in the treatment of osteoporosis.

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“…Furthermore, the latest prospective, nested case-control study results are consistent with the previous ones. Its authors underlined that plasma kisspeptin level seems to be a promising biomarker for miscarriage during the first trimester with the area under the receiver-operating characteristic curve of 0.874 (95% confidence interval [CI] 0.844–0.904) [ 84 ]. Unlike previous studies, the results of only one research available in the literature are inconclusive [ 85 ].…”

Section: Role Of Kisspeptin In the Pathogenesis Of Disorders From The...mentioning

confidence: 99%

The Role of Kisspeptin in the Pathogenesis of Pregnancy Complications: A Narrative Review

Szydełko-Gorzkowicz

Poniedziałek‐Czajkowska

Mierzyński

et al. 2022

IJMS

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Kisspeptins are the family of neuropeptide products of the KISS-1 gene that exert the biological action by binding with the G-protein coupled receptor 54 (GPR54), also known as the KISS-1 receptor. The kisspeptin level dramatically increases during pregnancy, and the placenta is supposed to be its primary source. The role of kisspeptin has already been widely studied in hypogonadotropic hypogonadism, fertility, puberty disorders, and insulin resistance-related conditions, including type 2 diabetes mellitus, polycystic ovary syndrome, and obesity. Gestational diabetes mellitus (GDM), preeclampsia (PE), preterm birth, fetal growth restriction (FGR), or spontaneous abortion affected 2 to 20% of pregnancies worldwide. Their occurrence is associated with numerous short and long-term consequences for mothers and newborns; hence, novel, non-invasive predictors of their development are intensively investigated. The study aims to present a comprehensive review emphasizing the role of kisspeptin in the most common pregnancy-related disorders and neonatal outcomes. The decreased level of kisspeptin is observed in women with GDM, FGR, and a high risk of spontaneous abortion. Nevertheless, there are still many inconsistencies in kisspeptin concentration in pregnancies with preterm birth or PE. Further research is needed to determine the usefulness of kisspeptin as an early marker of gestational and neonatal complications.

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Performance of plasma kisspeptin as a biomarker for miscarriage improves with gestational age during the first trimester

Abstract: Objective: To compare the performance of kisspeptin and beta human chorionic gonadotropin (bhCG), both alone and in combination, as biomarkers for miscarriage throughout the first trimester. Design: Prospective, nested case-control study.

Cited by 17 publications

References 56 publications

Kisspeptin in the Prediction of Pregnancy Complications

Kisspeptin in the Prediction of Pregnancy Complications

Acute Effects of Kisspeptin Administration on Bone Metabolism in Healthy Men

The Role of Kisspeptin in the Pathogenesis of Pregnancy Complications: A Narrative Review

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