Serum Kisspeptin Research Articles

Role of serum kisspeptin as a biomarker to detect miscarriage: a systematic review and meta-analysis.

Miscarriage is a common adverse pregnancy outcome with physical and emotional effects. Identifying predictive miscarriage biomarkers should improve early detection and management. Serum kisspeptin, known for its critical role in reproductive biology, has emerged as a potential biomarker for miscarriage. With this systematic review and meta-analysis, we aimed to assess the association between serum kisspeptin levels and the miscarriage risk. We systematically searched PubMed, Embase, and Cochrane Library databases for studies published up to February 2024, examining the association between serum kisspeptin levels and miscarriage. Eligible studies were observational designs that reported kisspeptin levels in women with and without miscarriage. We included 12 studies involving 2,050 participants. Pooled analysis demonstrated that low serum kisspeptin levels were significantly associated with an increased risk of miscarriage (standardized mean difference = -2.750; 95%CI: -4.357 to -1.143), with substantial heterogeneity (I2 = 98.7%). The pooled area under the curve from three studies indicated high diagnostic accuracy (AUC = 0.903; 95%CI: 0.860-0.946). Low serum kisspeptin levels are significantly associated with an increased miscarriage risk, suggesting that kisspeptin could serve as an effective biomarker for early detection. However, the significant heterogeneity among studies and the lack of standardized measurement protocols emphasize the necessity of further research before clinical implementation. SYSTEMATIC REVIEW REGISTRATION: (Registration ID: CRD42024520639).

Kisspeptin and DLK1 levels for monitoring treatment of girls with central precocious puberty.

Kisspeptin and delta-like 1 homolog (DLK1) are neuropeptides that reportedly play an important role in pubertal timing by activating and inhibiting the hypothalamic-pituitary-gonadal axis, respectively. Consequently, serum kisspeptin and DLK1 levels may be novel biomarkers for differentiating between central precocious puberty (CPP) and premature thelarche (PT) in girls and used to monitor CPP treatment. To compare baseline serum kisspeptin and DLK1 levels in girls with CPP at diagnosis and after treatment to age-matched girls with PT. This prospective longitudinal study included girls with precocious puberty and girls with PT who experienced breast development before 8 years of age and peak luteinizing hormone levels of ≥6 versus <6 IU/L after a gonadotropin-releasing hormone (GnRH) stimulation test. Serum kisspeptin and DLK1 levels were determined in both groups at baseline and after 6 months of GnRH analog treatment in the CPP group and analyzed by enzyme-linked immunosorbent assay. The study divided a total of 48 girls into CPP (n=24; mean age, 7.7±0.7 years) and PT (n=24; mean age, 7.4±0.8 years) groups. The baseline median serum kisspeptin levels were 50.5 pg/mL (range, 38.2-77 pg/mL) and 49.5 pg/mL (range, 39.7-67.6 pg/mL), respectively (P=0.89), while the baseline median serum DLK1 levels were 6.5 ng/mL (range, 5.9-7.5 ng/mL) and 6 ng/mL (4.4-14.4 ng/mL), respectively (P=0.68). After 6 months of GnRH analog treatment in the CPP group, the median serum kisspeptin level was lower (46.4 ng/mL; range, 37.1-60 ng/mL) than that at baseline (P=0.002), while the median serum DLK1 level was higher (7 ng/mL; range, 6.7-8.9) than that at baseline (P=0.002). Our findings suggest that baseline serum kisspeptin and DLK1 levels are not reliable biomarkers for differentiating between CPP and PT. However, significant changes in serum kisspeptin and DLK1 levels may be used to monitor CPP treatment.

Urinary phthalate/DINCH metabolites associations with kisspeptin and reproductive hormones in teenagers: A cross-sectional study from the HBM4EU aligned studies

BackgroundExposure to phthalate/DINCH metabolites can induce human reproductive toxicity, however, their endocrine-disrupting mechanisms are not fully elucidated. ObjectiveTo investigate the association between concentrations of phthalate/DINCH metabolites, serum kisspeptin, and reproductive hormones among European teenagers from three of the HBM4EU Aligned Studies. MethodsIn 733 Belgian (FLEHS IV study), Slovak (PCB cohort follow-up), and Spanish (BEA study) teenagers, ten phthalate and two DINCH metabolites were measured in urine by high-performance liquid chromatography-tandem mass spectrometry. Serum kisspeptin (kiss54) protein, follicle-stimulating hormone (FSH), total testosterone (TT), estradiol (E2), and sex hormone-binding globulin (SHBG) levels were measured by immunosorbent assays. Free Androgen Index (FAI) was calculated as a proxy of free testosterone. Adjusted sex-stratified linear regression models for individual studies, mixed effect models (LME) accounting for random effects for pooled studies, and g-computation and Bayesian kernel machine regression (BKMR) models for the phthalate/DINCH mixture were performed. ResultsThe LME suggested that each IQR increase in ln-transformed levels of several phthalates was associated with lower kisspeptin [MnBP: %change (95%CI): −2.8 (−4.2;-0.4); MEHP: −1.4 (−3.4,0.2)] and higher FSH [∑DINP: 11.8 (−0.6;25.1)] levels in females from pooled studies. G-computation showed that the phthalates/DINCH mixture was associated with lower kisspeptin [−4.28 (−8.07;-0.34)] and higher FSH [22.13 (0.5;48.4)] also in females; BKMR showed similar although non-significant pattern. In males, higher phthalates metabolites [MEHP: −12.22 (−21.09;-1.18); oxo-MEHP: −12.73 (−22.34;-1.93)] were associated with lower TT and FAI, although higher DINCH [OH-MINCH: 16.31 (6.23;27.35), cx-MINCH: 16.80 (7.03;27.46), ∑DINCH: 17.37 (7.26;29.74)] were associated with higher TT levels. No mixture associations were found in males. ConclusionWe observed sex-specific associations between urinary concentrations of phthalate/DINCH metabolites and the panel of selected effect biomarkers (kisspeptin and reproductive hormones). This suggests that exposure to phthalates would be associated with changes in kisspeptin levels, which would affect the HPG axis and thus influence reproductive health. However, further research is needed, particularly for phthalate replacements such as DINCH.

The Relation between serum Kisspeptin level in PCO women and its metabolic and hormonal profiles, Case control study

The Relation between serum Kisspeptin level in PCO women and its metabolic and hormonal profiles, Case control study

Kisspeptin levels in polycystic ovary syndrome and its manifestations

Background: The altered luteinizing hormone to follicle-stimulating hormone (LH/FSH) ratio- an important component in the pathogenesis of polycystic ovary syndrome (PCOS), is regulated by a brain peptide kisspeptin. This study aimed to explore the association of serum kisspeptin levels with PCOS and its manifestations. Methods: This cross-sectional study included 80 participants with PCOS on the basis of International evidence-based guidelines, 2018, and 71 healthy matched controls. Along with clinical information, fasting blood was drawn to measure total testosterone, sex hormone binding globulin, thyroid stimulating hormone, prolactin, 17-hydroxyprogesterone, and kisspeptin in all, and glucose, lipids, insulin, LH, FSH in only PCOS participants in the follicular phase of the menstrual cycle. Kisspeptin was measured by sandwiched enzyme-linked immunosorbent assay method with a lower limit detection level of 0.01 pg/mL. Result: Kisspeptin levels were undetectable in 25 out of 80 and 16 out of 71 controls. Among the participants with detection levels (55 in each group), kisspeptin did not differ between PCOS and control [31.2 (19.2 – 43.1) vs. 40.4 (14.9 – 70.4), pg/mL, p=0.446]. Among participants with PCOS, kisspeptin levels had no significant associations or correlations with any manifestations (ns for all). ROC curve analysis showed kisspeptin as not an acceptable marker for PCOS [AUC (95% CI): 0.57 (0.46 – 0.68), p= 0.221]. Conclusion: Our study failed to show any association of kisspeptin levels with PCOS and its manifestations.

Correlation of serum kisspeptin and leptin with non-obstructive azoospermia: A cross-sectional study in a subset of Karachi population.

To determine the association of serum kisspeptin, leptin, and other hormonal profile with non-obstructive azoospermia (NOA) in infertile male subjects. This cross-sectional study was conducted at Australian Concept Infertility Medical Center, and Ziauddin University, Karachi from March 2018 to March 2020. The duration of the study was two years. Serum samples of 106 azoospermic participants were taken. Division of the subjects was done on a histological basis into obstructive azoospermia (OA) n=36, NOA n=70 which were further divided into spermatid maturation arrest (SMA), n=41, and sertoli cell-only syndrome (SCOS) n=29. Serum kisspeptin and leptin were measured by ELISA (Cloud-Clone Corp). The follicle-stimulating hormone (FSH) (p<0.01), luteinizing hormone (LH) (p<0.01), thyroid-stimulating hormone (TSH) (p<0.01), and estradiol (p<0.01) was significantly high in the NOA group. However, kisspeptin was significantly decreased (p<0.01) in the NOA group. In the multivariate analysis after adjusting for other variables, the results showed that with the decrease in kisspeptin, the chances of being NOA were increased. Moreover, with the increase in Leptin, FSH, LH, and TSH the chances of being NOA were significantly enhanced. Serum kisspeptin, leptin, FSH, LH, TSH, and estradiol can be a potential marker for NOA in terms of better diagnosis, targeted therapeutic management, and the decision to proceed with surgical intervention.

#194 : Predictive Value of Serum Kisspeptin in Early First Trimester Pregnancy During IVF Treatment: A Prospective Study

Background and Aims: Kisspeptin is an emerging biomarker for the discrimination of viable pregnancy. The aim of the study is to determine whether serum kisspeptin can predict the first trimester miscarriage and compare it with serum hCG in the prediction of the first trimester miscarriage. Method: This study is a prospective case-control design including 178 women who had experienced early miscarriage (n = 21) and viable single pregnancy (n = 157), following frozen-thawed transfer (FET) from May 2019 to December 2019. Serum samples on 14 days, 21 days and 28 days after FET were collected for kisspeptin and hCG detection. Trial registration number: NCT03940495 Results: On day 21 after FET, serum kisspeptin levels were significantly lower in the early miscarriage group [0.260(0.185-0.375)] vs in the viable single pregnancy group [0.370(0.280–0.495)] (p=0.005). Similar results were showed on day 28 after FET, the serum kisspeptin levels were significantly lower in the early miscarriage group [0.27(0.2–0.33)] vs in the viable single pregnancy group [0.670(0.455–1.235)] (p&lt;0.001). But on day 14 after FET, serum kisspeptin levels were comparable in the early miscarriage group [0.260(0.210–0.325)] and in the viable single pregnancy group [0.280(0.215–0.340)] (p=0.551). Serum kisspeptin levels on day 21 and 28 have a poor predictive value of miscarriage compared with serum hCG levels. [Day 21: area under the curve = 0.687 (kisspeptin) and 0.816 (hCG); Day 28: area under the curve = 0.896 (kisspeptin) and 0.909 (hCG)]. Conclusion: Serum kisspeptin on day 14 failed to discriminate between miscarriage and ongoing pregnancies, and on day 21, 28 has a poor predictive value of miscarriage. Funding: This study was supported by the Special Project for Clinical Research in the Health Industry of the Shanghai Municipal Health Commission (20194Y0036).

A prospective study to evaluate whether serum kisspeptin is a marker predictive of the first-trimester miscarriage of women who conceive in IVF.

Kisspeptin is an emerging biomarker for the discrimination of viable pregnancy. The aim of the study is to determine whether serum kisspeptin can predict the first-trimester miscarriage and compare it with serum HCG in the prediction of the first-trimester miscarriage. This study is a prospective case-control design including 178 women who had experienced early miscarriage (n = 21) and viable single pregnancy (n = 157), following frozen-thawed embryo transfer (FET) from May to December 2019. Serum samples on 14days, 21days, and 28days after FET were collected for kisspeptin and HCG detection. NCT03940495. On day 21 after FET, serum kisspeptin levels were significantly lower in the early miscarriage group [0.260 (0.185-0.375)] vs in the viable single-pregnancy group [0.370 (0.280-0.495)] (p = 0.005). Similar results were shown on day 28 after FET, the serum kisspeptin levels were significantly lower in the early miscarriage group [0.270 (0.200-0.330)] vs in the viable single pregnancy group [0.670 (0.455-1.235)] (p < 0.001). But on day 14 after FET, serum kisspeptin levels were comparable in the early miscarriage group [0.260 (0.210-0.325)] and in the viable single-pregnancy group [0.280 (0.215-0.340)] (p = 0.551). Serum kisspeptin levels on days 21 and 28 have a poor predictive value of miscarriage compared with serum HCG levels. [Day 21: AUC = 0.687 (kisspeptin) and 0.816 (HCG); Day 28: AUC = 0.896 (kisspeptin) and 0.909 (HCG)]. Serum kisspeptin on day 14 failed to discriminate between miscarriage and ongoing pregnancies, and days 21 and 28 had poorpredictive values of miscarriage.

Prospective Study on the Association Between Serum Kisspeptin Levels, Vasomotor Symptoms, and Hormonal Profile in Perimenopausal and Early Postmenopausal Women

Prospective Study on the Association Between Serum Kisspeptin Levels, Vasomotor Symptoms, and Hormonal Profile in Perimenopausal and Early Postmenopausal Women

Serum kisspeptin is higher in hypertensive than non-hypertensive female subjects and positively correlated with systolic blood pressure.

Kisspeptin has a major role in reproductive regulation. Furthermore, it is also involved in metabolic and cardiovascular regulation as well as is a potent vasoconstrictor. This study aimed to: 1) determine correlations between serum kisspeptin levels with obesity/metabolic parameters; 2) compare parameters between non-hypertensive ([non-HT] N.=15) and hypertensive ([HT] N.=15) female subjects; and 3) determine correlations between leptin, systolic blood pressure (SBP) or diastolic blood pressure (DBP) with obesity and metabolic factors. Clinical parameters and fasting blood and adipose tissue samples were collected from women undergoing open abdominal surgery. Serum kisspeptin was not correlated with obesity parameters but was positively correlated with only SBP (P<0.05). Serum kisspeptin, SBP, DBP, body weight, waist circumference, hip circumference, plasma glucose, plasma insulin, the homeostatic model assessment for insulin resistance (HOMA-IR), and height of visceral adipocytes (VA) were higher but the Quantitative Insulin Sensitivity Check Index (QUICKI) was lower in hypertensive compared to non-hypertensive female subjects (P<0.05). Leptin was positively correlated with obesity and metabolic paramters including area, width, and perimeter of subcutaneous adipocytes, and area, width, height, and perimeter of VA (P<0.05) but was negatively correlated the QUICKI (P<0.001). SBP had positive correlations with insulin, glucose, HOMA-IR, and kisspeptin, but had a negative correlation with QUICKI (P<0.05). DBP had positive correlations with body weight, BMI, waist circumference, hip circumference, insulin, glucose, HOMA-IR, and width of VA (P<0.05), but had a negative correlation with the QUICKI (P<0.05). Kisspeptin, obesity especially visceral adiposity, and insulin resistance might contribute to increased blood pressure. Further studies are required to reveal the underlying mechanism of kisspeptin on metabolic and cardiovascular regulation.

Relationship between kisspeptin levels in the third trimester and late-onset fetal growth restriction: A case-control study

IntroductionWe aimed to investigate whether maternal serum kisspeptin levels are associated with late-onset FGR and contribute to adverse perinatal outcomes. MethodIn this case-control study, a total of 90 pregnant women admitted to the perinatology clinic were enrolled. Forty-five of them were diagnosed with FGR and 45 women with healthy pregnancies formed the control group. Maternal serum levels of kisspeptin 1 were compared. ResultsMedian kisspeptin1 serum levels were higher in the group of patients with FGR according to gestational age than in the control group [79.4(3.9–230.2) pg/mL vs. 39.8(0.4–188.3) pg/mL; p = 0.001]. The optimal cut-off value for kisspeptin1 was 30.32 pg/mL, with a positive predictive value of 64.6% (95% CI; 0.54–0.86), negative predictive value of 87.5% (95% CI; 0.44–0.72), positive likelihood ratio 1.75 (95% CI; 1.31–2.32), negative likelihood ratio 0.14 (95% CI; 0.04–0.44). DiscussionKisspeptin1 differed significantly in late-onset FGR compared with the control group. This difference from the control group can be used to estimate late-onset FGR.

P-691 Does serum Kisspeptin levels discriminate between fertile and infertile women with polycystic ovary syndrome?

Abstract Study question Does serum Kisspeptin (KP) levels discriminate between fertile and infertile women with polycystic ovary syndrome (PCOS)? Summary answer Serum KP levels can be used as a potential discriminatory biomarker for infertility in women with PCOS. What is known already PCOS is the most common cause of anovulatory infertility and not fully elucidated pathology. A persistent rapid gonadotropin-releasing hormone (GnRH) pulse frequency in patients with PCOS exist throughout ovulatory cycle. KP is a neuropeptide that increases GnRH pulsatile release during ovulation. Therefore, KP may have a key role as a central regulator of fertility in PCOS patients. Although, recent studies showed that the KP concentration is higher in PCOS patients, the evidence is limited as to whether serum KP levels determine infertility in PCOS. Study design, size, duration This was a single center prospective cohort study conducted at Goztepe Prof. Dr. Suleyman Yalcin City Hospital Affiliated to Istanbul Medeniyet University, Istanbul, Turkey between January 2023 to February 2023. Our study enrolled 30 fertile and 30 infertile women with PCOS, who were aged between 18 and 45 years. PCOS was defined according to the criteria of the Rotterdam ESHRE- ASRM sponsored consensus group (2004). Participants/materials, setting, methods Venous blood samples from the participants were obtained after fasting and between 8 a.m. and 10 a.m. on days 2-5 of the menstrual cycle. Samples were thawed, and a human KISS1 (Kisspeptin 1) ELISA kit (Elabscience, USA,lot no:E-EL-H5618) was applied to measure KP serum concentrations. Patient characteristics and KP concentrations were compared among the two groups. Statistical analysis was performed by Mann-Whitney, Spearman correlations, and linear regression analysis. A p-value &amp;lt;0.05 was considered significant. Main results and the role of chance The mean age of the patients was 27.57±5.39 years in the fertile PCOS group and 26.80± 4.85 years in the infertile PCOS group (p = 0.63). There was no significant difference among the groups in terms of body mass index (BMI), duration of infertility, serum FSH, LH, LH-to-FSH ratio, E2, antimullerian hormone (AMH), TSH, prolactin, 17OHP, total testosterone, SHBG, HbA1c, HOMA-IR, neutrophil–lymphocyte ratio levels and antral follicle count (AFC). DHEA-S was significantly higher in the infertile PCOS group (306.73±94.869 mcg/ dL), compared to the fertile PCOS group (258.08±84.29 mcg/ dL, p = 0.037). The mean KP level was significantly higher in the infertile PCOS group (444.80±136.61 ng/ mL), compared to the fertile PCOS group (333.02±131.10 ng/ mL, p = 0.001). The KP level was positively correlated with AFC, AMH, and total testosterone levels (R = 0.495, R = 0.548, R = 0.362, p &amp;lt; 0.05, respectively) in the infertile PCOS group. Furthermore, ROC analysis showed that the optimal cut-point value was found to be 285.59. When this cut-off value of serum KP levels was taken, the sensitivity was 0.96 and the specificity was 0.50. Linear regression analysis revealed that AMH was positively associated with KP levels (p = 0.022). Limitations, reasons for caution Due to the limited number of women with available samples, we were not able to analyze KP serum levels according to specific PCOS phenotypes Wider implications of the findings Serum KP levels are higher in infertile women with PCOS compared to fertile women with PCOS. Infertility caused by PCOS can be predicted by serum KP levels. In the future identification, KP in PCOS may be applied to develop potential therapeutic agents. Trial registration number Not applicable

Correlation between kisspeptin and biochemical markers in obese and non-obese women with polycystic ovary syndrome

Introduction The purpose of this study was to determine the association between kisspeptin levels and obesity in patients with polycystic ovary syndrome (PCOS) or in healthy controls and to explore the correlation between levels of kisspeptin and various endocrine and metabolic indices in each group. Methods From August 2020 to December 2021, the clinical data of 78 patients with polycystic ovary syndrome and 78 healthy individuals were collected. The two groups were further divided into obese and non-obese groups based on a BMI cutoff of 25. Serum kisspeptin levels were measured using enzyme linked immunosorbent assay (ELISA). Pearson’s correlation analysis was used to determine the correlation between PCOS and kisspeptin levels. Results The weight, body mass index (BMI), and waist circumference (WC), estradiol (E2), and testosterone (T) of the obese PCOS group were significantly higher than those of the study group (p < .05). WC, kisspeptin, triglycerides (TG), glucose (GLU), alanine amiotransferase (ALT), blood urea nitrogen (BUN), uric acid (UA), E2, luteinizing hormone (LH), prolactin (PRL), and T in the non-obese PCOS group were higher than those in the control group, and the difference was statistically significant (p < .05). Levels of E2 and TG in the obese PCOS group were significantly higher than those in the non-obese PCOS group (p < .05). Kisspeptin levels in the PCOS group exhibited a significant positive correlation with LH, T, and AMH levels; kisspeptin level positively correlated with T in the non-obese PCOS group and with anti-Müllerian hormone (AMH) in the obese PCOS group. Conclusion Serum kisspeptin levels are associated with hormone levels in patients with PCOS. Kisspeptin correlates with distinct biochemical indices in obese versus non-obese groups, indicating that kisspeptin may play a role in the prognostication, treatment, and clinical evaluation of patients with varying BMI.

Decreased neurokinin B as a risk factor of functional hypothalamic amenorrhea

Background Neurokinin B (NKB) belongs to the tachykinin family of proteins who’s regulation is essential for proper function of the reproductive system. It has been shown that patients with functional hypothalamic amenorrhea (FHA) exhibit decreased levels of serum kisspeptin. As kisspeptin secretion is regulated by NKB signaling, it is reasonable to suspect that patients with FHA will also have abnormal NKB secretion. Aim To assess NKB levels in patients with FHA and to determine whether NKB signaling is affected in these patients. We hypothesized that decreased NKB signaling is a factor contributing to the development of the FHA. Materials and methods A total of 147 patients with FHA and 88 healthy age-matched controls were enrolled. Baseline blood samples were drawn from both groups to measure serum concentrations of NKB, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin (PRL), thyroid-stimulating hormone (TSH), free thyroxine (fT4), cortisol, dehydroepiandrosterone sulfate (DHEA-S), testosterone (T), glucose, and insulin. Results Mean serum NKB levels were found to be decreased significantly in the FHA group when compared with the control group (628.35 ± 324.92 vs. 721.41 ± 337.57 ng/L, respectively p = 0.002). No statistical difference was observed in NKB-1 levels within the FHA group when selecting for normal and decreased body mass index. Conclusions Patients with FHA were found to have decreased serum NKB concentrations when compared to healthy controls. Abnormal NKB secretion is likely a key factor contributing to development of FHA.

Role of kisspeptin in polycystic ovarian syndrome: A metabolomics study.

Polycystic ovary syndrome (PCOS) is a pathophysiological disease affecting reproductive and metabolic indicators. Research has shown that kisspeptin might be involved in the regulation of pituitary hormone secretion and energy metabolism. The aim of this study was to investigate the relationship between serum kisspeptin levels and abnormal metabolism in PCOS. Fifty patients with PCOS and 50 control patients were recruited for this study. Serum kisspeptin levels were measured via ELISA. High-performance liquid chromatography-tandem mass spectrometry metabolomics was used to study the changes in serum metabolism between the PCOS and control groups. Serum kisspeptin levels were significantly elevated in individuals with PCOS compared with those in healthy controls (p = 0.011) and positively correlated with LH, T, FFA, BA, and LEP levels (p < 0.05). Significantly dysregulated expression of several metabolites was observed in the intergroup comparisons of the high-kisspeptin PCOS, low-kisspeptin PCOS, and healthy control groups. These primarily consisted of lipid, amino acid, and carbohydrate metabolites, among which palmitic acid and N-formylkynurenine levels were lower in the high-kisspeptin group than in controls. Metabolite set enrichment analysis was also performed based on metabolites in the KEGG database. The results showed that owing to the differences in kisspeptin concentrations in individuals with PCOS, there was a significant difference in amino acid and pyruvate metabolism. Kisspeptin could be a potential biomarker for the diagnosis of PCOS and plays an important role in metabolic regulation in individuals with PCOS. In addition, metabolomics provides a promising method for the study of metabolic abnormalities in individuals with PCOS, which might contribute to our understanding of its mechanisms.

Serum kisspeptin, neurokinin Band inhibin B levels can be used as alternative parameters to distinguish idiopathic CPP from premature thelarche in the early stages of puberty.

There is controversial results about serum kisspeptin, neurokinin-B (NKB), anti-Müllerian hormone (AMH)and inhibin B (INHB) levels in girls with central precocious puberty (CPP). Aim of this study is to evaluate serum levels of these four peptides in patients presented with early pubertal signs, and to evaluate their diagnostic validity in the diagnosis of CPP. Cross-sectional study. Study included 99 girls (51 CPP, 48 premature thelarche [PT]) whose breast development started before 8 years and 42 age-matched healthy prepubertal girls. Clinical findings, antropometric measurements, laboratory and radiological findings were recorded. Gonadotropin-releasing hormone (GnRH) stimulation test was performed in all cases with early breast development. Kisspeptin, NKB, INHBand AMH levels were measured in fasting serum samples using enzyme-linked immunosorbent assay method. There was no statistically significant difference between mean ages of girls with CPP (7.1 ± 1.2 years), PT (7.2 ± 1.3 years)and prepubertal controls (7.0 ± 1.0 years). Serum kisspeptin, NKBand INHB levels were higher in CPP group compared to PT and control groups, while serum AMH level was lower in CPP group. Serum kisspeptin, NKB, and INHB were all positively correlated with bone age (BA) advancement, and peak luteinizing hormonein GnRH test. Multiple stepwise regression analysis revealed that the most important factors used to differentiate CPP from PT were advanced BA, serum kisspeptin, NKB and INHB levels (AUC: 0.819, p < .001). We, firstshowed in the same patients' group that serum kisspeptin, NKB and INHB were higher in patients with CPP and can be used as alternative parameters to distinguish CPP from PT.

Correlation of serum kisspeptin levels, ovarian kisspeptin expression, and ovarian BMP15 expression in rat model of polycystic ovarian syndrome

Background: Kisspeptin is a neuropeptide that has an important role in the female reproductive cycle which is indicated by its role in regulating the hypothalamic-pituitary-gonadal axis (HPG axis). Aims: To analyze the correlation between serum kisspeptin levels, ovarian kisspeptin expression, and ovarian BMP15 expression in PCOS model rats. Methods: The research was true experimental research with post-test design only control group, was carried out from August to October 2022 at the Faculty of Veterinary Medicine Universitas Airlangga. 32 Rattus novergicus rats were divided into a control group and PCOS model group. Blood serum and ovaries were obtained from all groups. Blood serum was examined for kisspeptin levels by ELISA technique, kisspeptin expression, and BMP15 Ovaries were examined immunihistochemically. Results: Serum kisspeptin levels and ovarian kisspeptin expression of the PCOS model group were not significantly higher than those of the control group (p&gt;0.05, p&gt;0.05). The ovarian BMP15 expression of the PCOS model group was not significantly lower (p&gt;0.05) than that of the control group. Ovarian kisspeptin expression and ovarian BMP15 expression did not have a significant correlation with serum kisspeptin levels (p&gt;0.05). In contrast, there was a significant correlation (p&lt;0.05) between ovarian kisspeptin expression and ovarian BMP15 expression. Conclusion: Serum kisspeptin levels and ovarian kisspeptin expression of the PCOS model group were not higher than those of the control group and the ovarian BMP15 expression of the PCOS model group was not lower than that of the control group. There was no correlation between serum kisspeptin levels with ovarian kisspeptin expression and ovarian BMP15 expression. A significant correlation was found between ovarian kisspeptin expression and ovarian BMP15 expression.

Effects of obesity on the serum BMP15, GDF9, and kisspeptin concentrations in women of reproductive age.

As BMP15, GDF9, and kisspeptin all play critical roles in folliculogenesis and fertilization, investigating the possible relationship between obesity and these three factors could prove crucial in relation to understanding the role of obesity in infertility. Thus, the present study sought to determine the effects of obesity on the serum BMP15, GDF9, and kisspeptin concentrations in women of reproductive age. Ninety female participants were equally divided into three groups: class-1 obese (n=30), class-2 obese (n=30), and normal weight (control; n=30). The participants' serum BMP15, GDF9, and AMH concentrations were measured. Moreover, the serum kisspeptin concentrations were evaluated in the class-1 obese and control groups by means of the enzyme-linked immunosorbent assay (ELISA) method while the participants were in their menstrual period. The serum BMP15 and kisspeptin concentrations were found to be much higher in the control group than in both obese groups (p=0.001 and p=0.01, respectively). While the GDF9 concentration exhibited a statistically significant positive correlation with age, the BMP15 concentration exhibited a positive correlation with the kisspeptin and LH concentrations in the control group. In addition, a positive correlation was identified between the BMP15 concentration and both age and the glucose level and a negative correlation with the insulin level in both the obese groups. Obesity appears to reduce the serum BMP15 and kisspeptin concentrations in obese women of reproductive age. This reduction may represent a milestone in reproductive dysfunction and may be used to predict the success of infertility treatment in obese women.

Serum kisspeptin levels mainly depend on ovarian expression of Kiss1 mRNA in female rats.

The hypothalamic kisspeptin/KISS1 receptor system is essential for puberty onset and reproductive development. Although serum kisspeptin might be associated with puberty, its levels, according to developmental stage, and its origin still remain unclear. This study evaluated the changes in serum kisspeptin levels during puberty and the corresponding Kiss1 mRNA and protein expression in various organs of female rats to identify the source of serum kisspeptin. Tissues from several organs, including the ovaries and anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) in the hypothalamus, were obtained for assessing Kiss1 mRNA and protein expressions. Serum kisspeptin levels progressively increased with developmental stages until the peripubertal stage. The ovaries showed the highest Kiss1 expression among the organs examined. Next, we explored the changes in serum kisspeptin levels and hypothalamic Kiss1 expression in ovariectomized and estradiol-treated ovariectomized rats. Serum kisspeptin levels decreased regardless of estradiol treatment; Kiss1 expression was enhanced by ovariectomy and estradiol treatment in the ARC, while it was decreased by ovariectomy and enhanced by estradiol in the AVPV, suggesting that serum kisspeptin may be associated with pubertal development and mainly depended on ovarian Kiss1 expression. Thus, serum kisspeptin levels are associated with puberty and may serve as a downstream marker of ovarian reproductive function.

Follicular Dynamics and Endocrine Profile during Normal Estrous Cycle and Early Pregnancy in Surti Buffaloes

The study was conducted on Surti buffaloes for follicular dynamics and endocrine profile during normal estrous cycle (n=6) and early pregnancy (n=6). In cyclic and early pregnant buffaloes, one-wave (33.33% vs. 50.00%) and two-waves (66.66% vs. 50.00%) follicular development was recorded, without three-wave pattern. In cyclic buffalo, the length of estrous cycle and duration of inter-ovulatory interval were little shorter in one wave cycles than in two wave cycles (22.50±0.50 and 23.25±0.25 days). The number of follicles differed non-significantly within and between cyclic and early pregnant buffaloes. The mean maximum diameter of dominant follicle of second wave was significantly larger in cyclic than early pregnant animals for two wave pattern (1.09±0.02 vs 0.73±0.02 cm). In cyclic buffaloes, the mean maximum CL size recorded was 1.21±0.02 and 1.52±0.05 cm (P&lt;0.05) in one- and two-wave cycles, respectively, whereas in early pregnant buffaloes, the corresponding CL size was 1.50±0.04 and 1.55±0.07 cm without significant difference. Thus the mean maximum CL size of early pregnant buffaloes was significantly larger than the cyclic buffaloes with one-wave cycle (1.50±0.04 vs. 1.21±0.02 cm). In the normal cyclic animals, the CL size increased gradually up to day 8 (1.30±0.04 cm) and then remained stable up to day 18 (1.26±0.15 cm), followed by regression and display of next estrus between day 19 and 21, whereas in early pregnant animals the CL size gradually increased up to day 10 (1.48±0.07 cm) and then it was maintained till day 22 (1.46±0.04 cm) of monitoring. The mean diameter of largest follicle recorded was on the day of estrus (0.98±0.07 cm) with variable development of follicles during metestrus to diestrus phase with a new follicles developed during proestrus to estrus phase reaching maximum diameter of ovulatory size (0.99±0.09 cm) between days 19 and 21, whereas in early pregnant animals, the diameter of larger follicle (0.76±0.05 cm) was not recorded up to ovulatory size. The mean concentrations of serum progesterone were lowest during peri-estrus phase, increased through early-luteal phase to a maximum concentration during mid-luteal phase (4.50±0.88 to 4.67±0.95 ng/ml) and then gradually declined through late-luteal phase of diestrus in normal cyclic animals with inverse trend in estradiol profile. However, in early pregnant animals the progesterone levels gradually increased initially and then were maintained higher (6.17±0.32 to 8.13±0.55 ng/ml) with basal estradiol throughout the luteal phase. The serum progesterone/estradiol levels were in harmony with the ovarian dynamics in both cyclic and early pregnant buffaloes. The mean concentrations of serum FSH, LH and kisspeptin in normal cyclic and early pregnant animals did not vary statistically between periods within the status or between reproductive status of animals at any of the periods. The concentration of serum kisspeptin dropped significantly in advanced pregnancy as compared to first and second trimester.