Search Results (38)

The pituitary and gonads serve as central regulatory hubs and functional organs for gametogenesis and maturation. In this study, we performed single-cell RNA sequencing (scRNA-seq) of the pituitary and ovary in pre-spawning Pelteobagrus fulvidraco to elucidate the cellular landscape and regulatory pathways governing gonadal development and oocyte maturation. Pituitaries from four female fish (weight: 43.8 ± 3.2 g; length: 14.1 ± 0.7 cm) and four male fish (weight: 78.2 ± 11.2 g; length: 18.9 ± 1.1 cm) were subjected to single-cell transcriptomic analysis. A total of 17 distinct cell types were identified in the female pituitary, whereas 15 cell types were detected in the male pituitary. Both male and female pituitaries comprised multiple hormone-secreting endocrine populations, indicating a largely conserved cellular composition. However, sex-specific differences were observed in thyrotrope subtypes, suggesting potential sexual dimorphism in pituitary endocrine regulation. Examination of receptor gene expression revealed cell-type-specific regulatory capacities, highlighting gonadotropin, steroid, and neuropeptide responsiveness across pituitary populations. In the ovary, 10 cell types were identified, with granulosa cells (~22.9%) and theca cells (~8.6%) showing distinct transcriptional profiles. Follicle-stimulating hormone receptor (fshr) was highly expressed in granulosa cells, whereas luteinizing hormone receptor (lhcgr) and steroidogenic genes (hsd3b1, pgr) were predominantly localized in theca cells, indicating functional compartmentalization of gonadotropin and steroid signaling. Prostaglandin (PG) and melatonin (MT) pathways were implicated in paracrine regulation: the prostaglandin synthase ptgs2a was expressed in theca, germ, and immune cells, while ptger2a was expressed in granulosa cells; melatonin synthesis genes (aanat1, aanat2, asmtl) were confined to granulosa cells, with receptors (mtnr1ab) in germ cells. These findings suggest that ovarian paracrine signaling complements systemic endocrine control to modulate oocyte maturation and ovulation. This single-cell atlas provides a high-resolution framework of reproductive cell types and signaling networks in P. fulvidraco, offering insights for improving artificial breeding and reproductive management in aquaculture. Full article

Background/Objectives: Growing evidence indicates that melatonin contributes to kidney development and function, while disruptions of fetal circadian signaling have been linked to congenital anomalies of the kidney and urinary tract (CAKUT). This study aimed to characterize the developmental and spatial expression patterns of melatonin receptors MTNR1A and MTNR1B in normal human fetal kidneys and in CAKUT phenotypes. Methods: This study analyzed 40 human fetal kidney specimens, including healthy controls and CAKUT cases (horseshoe kidneys, duplex kidneys, and dysplastic kidneys), obtained from spontaneous abortions and pregnancy terminations. Samples were classified into developmental phases Ph2–Ph4 according to established morphological criteria. Immunofluorescence staining was used to visualize MTNR1A and MTNR1B expression. Quantitative analysis was performed using ImageJ, measuring the fluorescence area percentage. Statistical comparisons were conducted using a two-way ANOVA. Results: In control kidneys, MTNR1A expression was predominantly observed in glomeruli and interstitial cells and showed a descending trend across developmental stages, whereas MTNR1B was localized to glomeruli and strongly to the apical membranes of tubules, particularly distal tubules, without substantial developmental variation. CAKUT phenotypes exhibited higher expression of both receptors compared to controls. Significant phase-dependent differences in MTNR1A expression were observed in horseshoe, duplex, and dysplastic kidneys. MTNR1B expression decreased across developmental stages in dysplastic kidneys and differed significantly between Ph3 and Ph4 in duplex kidneys. At Ph3, duplex kidneys showed the highest MTNR1B expression. Conclusions: Altered developmental expression patterns of MTNR1A and MTNR1B in CAKUT suggest an association between melatonin signaling and abnormal human kidney development. Full article

Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication with significant short- and long-term consequences for mothers and offspring. While environmental factors, such as obesity and diet, contribute to the risk, genetic predisposition also plays a role in the pathogenesis of GDM. Genome-wide association studies have identified multiple susceptibility loci, including MTNR1B, CDKAL1, and IRS1, which represent mechanistically distinct pathways affecting β-cell function, insulin secretion, and peripheral insulin signaling. This review provides a unified mechanistic framework explaining why these three genes, despite individually modest effect sizes, offer complementary insights into GDM pathophysiology that extend beyond other established loci such as TCF7L2. We critically evaluate the current evidence for genetic risk scores in GDM prediction, acknowledging that their incremental predictive value beyond traditional clinical factors remains modest AUC improvement typically <0.05). The integration of genetic variants with epigenetic modifications is discussed, with careful attention to distinguishing causal mechanisms from correlative findings. We emphasize significant limitations in current research, including population stratification, winner’s curse effects, and the predominance of East Asian cohorts. While genetic insights may eventually inform risk stratification, substantial barriers remain before clinical implementation, including insufficient predictive accuracy, lack of cost-effectiveness data, and limited generalizability across diverse populations. Future directions include integrating multi-omics data, developing ethnically validated polygenic risk scores, and conducting pragmatic randomized controlled trials to establish the clinical utility of precision prevention strategies. Full article

Background: Gestational diabetes mellitus (GDM) poses a growing public health challenge worldwide due to its increasing prevalence, associated pregnancy complications, and long-term metabolic risks for both mothers and offspring. Genetic factors are known to contribute to GDM susceptibility, yet little is known about their relevance in ethnic Kazakh population. The primary objective of this study was to evaluate associations between selected candidate SNPs involved in β-cell function and the risk of GDM in a Kazakh cohort. Secondary objectives included the assessment of potential gene–gene interactions. Methods: We conducted a case–control study among 365 pregnant Kazakh women. Of these, 217 were diagnosed with GDM, and 148 had normal glucose tolerance. Clinical and genealogical data were collected. Eight candidate SNPs that were previously associated with GDM or glucose metabolism were genotyped. Logistic regression was used to assess associations between SNPs and GDM risk. Gene–gene interactions were evaluated using multifactor dimensionality reduction (MDR). Results: In univariate analysis, MTNR1B rs10830963 demonstrated a statistically significant association under the additive model (OR 0.61, 95% CI 0.42–0.89), indicating a potential protective effect of the C allele. However, this association was not statistically significant after multivariable adjustment (adjusted OR 0.58, 95% CI 0.32–1.03) and correction for multiple testing. In the adjusted analysis, TCF7L2 rs7903146 showed a significant association under the dominant model (adjusted OR 2.29, 95% CI 1.01–5.46); however, this finding did not remain significant following FDR correction. MDR analysis showed that the best two-locus model included IGF2BP2 rs4402960 and CDKAL1 rs7754840 (CVC = 6/10; testing accuracy = 0.558; permutation p < 0.001). The most stable interaction was observed for the three-locus model comprising IGF2BP2 rs4402960, MTNR1B rs10830963, and PPARG rs1801282 (CVC = 9/10; testing accuracy = 0.576; permutation p < 0.001). Conclusions: The findings suggest that common variants in IGF2BP2, CDKAL1, MTNR1B, TCF7L2, PPARG, and GCK do not exert strong individual effects on GDM susceptibility in this cohort of ethnic Kazakh women. Instead, the results are more consistent with a modest polygenic architecture characterized by small effect sizes and possible weak gene–gene interactions. MDR analysis identified statistically significant interaction models; however, their limited predictive accuracy indicates that these findings should be interpreted as exploratory. Full article

Although the MTNR1B single nucleotide polymorphism rs10830963 has been strongly associated with the onset of type 2 diabetes (T2D), its association with the progression and prognosis of T2D has been understudied. We conducted this prospective analysis based on the UK Biobank cohort study. Microvascular complications (MIC) of T2D in this study included diabetic retinopathy, diabetic neuropathy, and diabetic kidney disease. Macrovascular complications (MAC) of T2D included diabetic coronary artery disease, diabetic cerebrovascular disease, and diabetic peripheral vascular disease. The multi-state model was used to analyze the association between the polymorphism of rs10830963 and the trajectory of T2D. The accelerated failure time (AFT) model was used to assess the association between rs10830963 and the onset of T2D and T2D comorbidities. A total of 283,531 middle- and old-age participants were included. During a median follow-up of 13.7 years, 11,947 participants developed T2D, 1556 participants developed MIC, 1797 participants developed MAC, and 618 participants died. In the additive model, the G risk allele of rs10830963 was significantly associated with an increased risk of the transition from T2D-free to T2D (HR = 1.050, 95% CI: 1.020, 1.079) and a decreased risk of the transition from T2D to MIC (HR = 0.918, 95% CI: 0.850, 0.992), particularly from T2D to diabetic retinopathy (HR = 0.882, 95% CI: 0.782, 0.995). Besides, the G risk allele of rs10830963 accelerated the transition from T2D-free to T2D (Time Ratio [TR] = 0.966, 95% CI: 0.947, 0.986) and slowed down the transition from T2D to MIC (TR = 1.067, 95% CI: 1.030, 1.105). The MTNR1B single nucleotide polymorphism rs10830963 was associated with an increased risk of T2D and a decreased risk of MIC, particularly diabetic retinopathy among T2D individuals. Our results highlight that rs10830963 might play differential roles in the onset and progression of T2D. Full article

Background: Polycystic ovary syndrome (PCOS) is a complex and multifactorial disorder affecting reproductive, endocrine, and metabolic functions in women of reproductive age. While environmental and lifestyle factors play a role, increasing evidence highlights the contribution of genetic and epigenetic mechanisms to its pathogenesis. Objective: This narrative review aims to provide an updated overview of the current evidence regarding the role of genetic variants, gene expression patterns, and epigenetic modifications in the etiopathogenesis of PCOS, with a focus on their impact on ovarian function, fertility, and systemic alterations. Methods: A comprehensive search was conducted across MEDLINE, EMBASE, PubMed, Web of Science, and the Cochrane Library using MeSH terms including “PCOS”, “Genes involved in PCOS”, and “Etiopathogenesis of PCOS” from January 2015 to June 2025. The selection process followed the SANRA quality criteria for narrative reviews. Seventeen studies published in English were included, focusing on original data regarding gene expression, polymorphisms, and epigenetic changes associated with PCOS. Results: The studies analyzed revealed a wide array of molecular alterations in PCOS, including the dysregulation of SIRT and estrogen receptor genes, altered transcriptome profiles in cumulus cells, and the involvement of long non-coding RNAs and circular RNAs in granulosa cell function and endometrial receptivity. Epigenetic mechanisms such as the DNA methylation of TGF-β1 and inflammation-related signaling pathways (e.g., TLR4/NF-κB/NLRP3) were also implicated. Some genetic variants—particularly in DENND1A, THADA, and MTNR1B—exhibit signs of positive evolutionary selection, suggesting possible ancestral adaptive roles. Conclusions: PCOS is increasingly recognized as a syndrome with a strong genetic and epigenetic background. The identification of specific molecular signatures holds promise for the development of personalized diagnostic markers and therapeutic targets. Future research should focus on large-scale genomic studies and functional validation to better understand gene–environment interactions and their influence on phenotypic variability in PCOS. Full article

Background/Objective: The single-nucleotide polymorphism (SNP) rs10830963 in the melatonin receptor 1B (MTNR1B) gene influences insulin secretion and glucose metabolism and has been associated with an increased risk of type-2 diabetes. This study aimed to explore the interaction between dietary intake and the MTNR1B rs10830963 polymorphism on glycemic profiles in young Brazilian adults. Methods: This cross-sectional study assessed 200 healthy young adults (19–24 years), evaluating the MTNR1B rs10830963 genotype, anthropometric parameters, glycemic markers (fasting insulin, glucose, HOMA-IR, and HOMA-β), and dietary intake via three 24 h dietary recalls. Genotype–diet interactions were tested using multivariate linear regression models adjusted for confounders. Results: The carriers of the G allele exhibited a positive association with fasting insulin levels (p = 0.003), insulin/glucose ratio (p = 0.004), HOMA-IR (p = 0.003), and HOMA-β (p = 0.018). Energy-adjusted fiber intake showed a significant genotype-specific interaction only in carriers of the G allele, where higher dietary fiber intake was significantly associated with lower fasting insulin (p_interaction = 0.034) and HOMA-IR (p_interaction = 0.028). Conclusion: Our findings indicate that the MTNR1B rs10830963 polymorphism is associated with glycemic markers, and dietary fiber intake may attenuate the adverse effects of the MTNR1B rs10830963 G allele on glycemic profiles in young Brazilian adults. This highlights the potential role of fiber in improving health outcomes for individuals carrying this risk allele. To validate these results and assess the broader implications for the Brazilian population, further intervention studies and larger-scale research are essential. Full article

Hashimoto’s thyroiditis (HT) is an autoimmune disorder of the thyroid gland characterized by chronic inflammation, which in most cases results in hypothyroidism. The melatonin receptor MTNR1B is sporadically expressed in the thyroid gland. It modulates immune responses, and alterations in the melatonin–MTNR1B receptor signaling pathway may play a role in developing autoimmune diseases. Obesity worsens the severity and progression of some autoimmune diseases and reduces treatment efficacy. This study aimed to investigate the association of MTNR1B gene polymorphisms (rs10830963, rs1387153, and rs4753426) with HT with regards to the body mass index (BMI). Patients with HT were categorized into normal weight BMI ≤ 25 kg/m² and overweight/obese BMI > 25 kg/m² groups. This study included 115 patients with a clinical-, ultrasound-, and laboratory-confirmed diagnosis of HT (64 normal-weight patients and 51 overweight/obese patients) with a mean age of 43 ± 12 years. The results showed that specific MTNR1B polymorphisms are associated with obesity in HT patients. BMI was found to be associated with the rs10830963 polymorphism, and the G allele and GG genotype of the rs10830963 polymorphism were more common in overweight/obese HT patients. Furthermore, the results suggest that genetic factors associated with BMI play a role in developing HT and open new possibilities for personalized treatment approaches. Full article

Growth traits are crucial for poultry breeding and production. Marker-assisted selection (MAS) and genomic selection (GS) of growth traits require a substantial number of accurate genetic markers. A genome-wide association study (GWAS) for body size traits was performed on 248 Luning chickens to identify significant single-nucleotide polymorphisms (SNPs) and insertions and deletions (INDELs) related to the growth and development of chickens. A total of 30 significant SNPs and 13 INDELs were obtained for body size traits. Two notable regions, spanning from 43.072 to 43.219 Mb on chromosome 1 and from 4.751 to 4.800 Mb on chromosome 11, were found to be significantly associated with growth traits in the GWAS of both SNPs and INDELs. Some genes, including PPFIA2, KITLG, DUSP6, TOX3, MTNR1B, FAT3, PTPRR, VEZT, BBS9, and CYLD, were identified as important candidate genes for the growth of chickens. The results provide valuable information for understanding the genetic basis of growth traits which is beneficial for the subsequent selective breeding in Luning chickens. Full article

Melatonin is a critical regulator of biological rhythms across organisms, transducing light signals into neuroendocrine signals that facilitate reproductive regulation in response to environmental cues. However, the precise mechanisms through which melatonin regulates reproduction in fish require further investigation. In this study, we employed molecular and organizational biological techniques to examine the expression patterns of melatonin and its five receptor subtypes (LcMTNR1A1, LcMTNR1A2, LcMTNR1B1, LcMTNR1B2, and LcMTNR1C) in various tissues of the large yellow croaker (Larimichthys crocea). Our results revealed significant expression of all receptors in the pituitary and testes, with distinct gender differences, including a lack of expression in the ovary. Moreover, our data indicate that melatonin and its receptors are primarily expressed during stage III, highlighting their role in sexual maturity. Enzyme- linked immunosorbent assay (ELISA) results further demonstrated that in vitro melatonin incubation in the brain of L. crocea influenced gonadotropin-releasing hormone (GnRH) and testosterone secretion in a dose-dependent manner, suggesting actions beyond the classical hypothalamic–pituitary–gonadal (HPG) axis. Overall, our findings provide new evidence supporting the role of the melatonin system in reproductive regulation in marine teleosts. Full article

Obesity has emerged as a major risk factor for human health, exacerbated by aging and changes in dietary habits. It represents a significant health challenge, particularly for older people. While numerous studies have examined the effects of obesity and aging on fat metabolism independently, research on their combined effects is limited. In the present study, the protective action against white fat accumulation after a high-fat diet (HFD) exerted by exogenous melatonin, a circadian hormone endowed with antioxidant properties also involved in fat metabolism, was investigated in a mouse model. For this purpose, a battery of tests was applied before and after the dietary and melatonin treatments of the animals, including epididymal white adipose tissue (eWAT) histological evaluations, transcriptomic and lipidomic analyses, real-time PCR tests, immunofluorescence staining, Western blot, the appraisal of serum melatonin levels, and transmission electron microscopy. This study found that aged mice on a high-fat diet (HFD) showed increased lipid deposition, inflammation, and reduced antioxidant glutathione (GSH) levels compared to younger mice. Lipidomic and transcriptomic analyses revealed elevated triglycerides, diglycerides, ceramides, and cholesterol, along with decreased sphingomyelin and fatty acids in eWAT. The genes linked to inflammation, NF-κB signaling, autophagy, and lipid metabolism, particularly the melatonin and glutathione pathways, were significantly altered. The aged HFD mice also exhibited reduced melatonin levels in serum and eWAT. Melatonin supplementation reduced lipid deposition, increased melatonin and GSH levels, and upregulated AANAT and MTNR1A expression in eWAT, suggesting that melatonin alleviates eWAT damage via the MTNR1A pathway. It also suppressed inflammatory markers (e.g., TNF-α, NLRP3, NF-κB, IL-1β, and CEBPB) and preserved mitochondrial function through enhanced mitophagy. This study highlights how aging and HFD affect lipid metabolism and gene expression, offering potential intervention strategies. These findings provide important insights into the mechanisms of fat deposition associated with aging and a high-fat diet, suggesting potential intervention strategies. Full article

Introduction. Melatonin and serotonin can influence certain aging processes in the ovaries. The main melatonin receptors are represented by types MT1 and MT2. The goal of investigation. Here, we evaluated the expression of genes and synthesis of MT1 and MT2 receptors, as well as serotonin synthesis in the ovaries during ontogenesis. Methods. We analyzed histological material obtained from the ovaries of infants, women of younger and older reproductive age, premenopausal, menopausal, and postmenopausal women. For the analysis of MT1 and MT2 receptors and serotonin expression and synthesis, RT-PCR and immunohistochemistry were used. Results. We found that the synthesis of serotonin, as well as MT1 and MT2 receptors in the ovaries significantly decrease in ontogenesis. The sharpest drop in these molecules was observed in samples obtained from one-year-old infants, as well as from pubescent girls and menopausal women. A statistically significant 2.3–7.6-fold decrease in the expression of MTNR1A and MTNR1B genes in the ovaries was also observed in one-year-old infants, in adolescents, and in middle-aged women. Conclusions. These data are crucial to understanding the fundamental mechanisms of aging of the female reproductive system and the search for molecules predicting its aging. Full article

Melatonin, noted for its anti-cancer properties in various malignancies, including cutaneous melanoma, shows promise in Uveal melanoma (UM) treatment. This study aimed to evaluate melatonin receptor expression in primary UM and its association with UM-related mortality and prognostic factors. Immunohistochemical analysis of 47 primary UM tissues showed low expression of melatonin receptor 1A (MTNR1A) and melatonin receptor 1B (MTNR1B), with MTNR1A significantly higher in patients who succumbed to UM. Analysis of TCGA data from 80 UM patients revealed RNA expression for MTNR1A, retinoic acid-related orphan receptor alpha (RORα), and N-ribosyldihydronicotinamide:quinone oxidoreductase (NQO2), but not MTNR1B or G protein-coupled receptor 50 (GPR50). Higher MTNR1A RNA levels were observed in patients with a BRCA1 Associated Protein 1 (BAP1) mutation, and higher NQO2 RNA levels were noted in patients with the epithelioid tumor cell type. However, Kaplan–Meier analysis did not show distinct survival probabilities based on receptor expression. This study concludes that UM clinical samples express melatonin receptors, suggesting a potential mechanism for melatonin’s anti-cancer effects. Despite finding higher MTNR1A expression in patients who died of UM, no survival differences were observed. Full article

Seasonality in sheep reproduction and related limitations make milk production challenging throughout the year. In the present study, we investigated the response to estrus induction treatments in three indigenous breeds, Florina, Chios, and Karagouniko, as well as the melatonin receptor 1A gene variants in relation to this response. The three distinct synchronization methods were A: intravaginal sponges, B: GNRH use, and C: male effect. In group A, fertility was 85%, and Florina ewes expressed estrus at 90% in July. Ewes from Karagouniko and Chios had fecundity rates of 95% and 99%, respectively, and 100% estrus expression. The Florina ewes in group B expressed estrus at a percentage of 60%, with a fecundity rate of 57%, the Karagouniko ewes at a percentage of 65%, with a fecundity rate of 54%, and the Chios breed animals at a percentage of 87%, with a fecundity rate of 85%. Twenty to twenty-five days after ram induction, 68% of the Florina breed in group C showed signs of estrus, compared to 84% and 94% of Karagouniko and Chios breeds, respectively. In both Florina and Karagouniko breeds, all treatments showed a substantial difference in the frequency of the four identified SNPs in the MTNR1A gene between ewes who expressed estrus and ewes who did not. The genetic improvement based on the alleles analyzed in the current study is expected to decrease seasonality rates in indigenous sheep breeds. Full article

Pregnancy is a highly intricate and delicate process, where inflammation during early stages may lead to pregnancy loss or defective implantation. Melatonin, primarily produced by the pineal gland, exerts several pharmacological effects. N6-methyladenosine (m6A) is the most prevalent mRNA modification in eukaryotes. This study aimed to investigate the association between melatonin and m6A during pregnancy and elucidate the underlying protective mechanism of melatonin. Melatonin was found to alleviate lipopolysaccharide (LPS)-induced reductions in the number of implantation sites. Additionally, it mitigated the activation of inflammation, autophagy, and apoptosis pathways, thereby protecting the pregnancy process in mice. The study also revealed that melatonin regulates uterine m6A methylation levels and counteracts abnormal changes in m6A modification of various genes following LPS stimulation. Furthermore, melatonin was shown to regulate m6A methylation through melatonin receptor 1B (MTNR1B) and subsequently modulate inflammation, autophagy, and apoptosis through m6A. In conclusion, our study demonstrates that melatonin protects pregnancy by influencing inflammation, autophagy, and apoptosis pathways in an m6A-dependent manner via MTNR1B. These findings provide valuable insights into the mechanisms underlying melatonin’s protective effects during pregnancy and may have implications for potential therapeutic strategies in managing pregnancy-related complications. Full article