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Rosacea and autoimmune liver diseases (AILDs) are diseases closely associated with immune system abnormalities. AILDs primarily includes autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Currently, research on the association between these two conditions is limited. Therefore, this study employed the bidirectional Mendelian randomization (MR) method to investigate potential causal relationships between rosacea and AILDs based on genetic predictions. Summary data related to Rosacea, AIH, PSC, and PBC were obtained from public genome-wide association studies (GWAS). The inverse variance weighted (IVW) method was used as the primary analytical approach, supplemented by the MR-Egger, weighted mode method, weighted median, and simple mode. A series of sensitivity analyses were also conducted to identify heterogeneity and pleiotropy effects. The MR analysis results indicated a significant increase in the risk of rosacea being associated with PBC (OR = 1.09, 95% CI = 1.02-1.18, P = 0.014), but no such association was found with AIH or PSC. Furthermore, this study did not find a significant impact of rosacea on the risk of AILDs. This study represents the first in-depth exploration of the potential causal relationship between rosacea and AILDs using MR analysis. Thes findings suggest an increased risk of rosacea among PBC patients.
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Colangitis Esclerosante , Estudio de Asociación del Genoma Completo , Hepatitis Autoinmune , Cirrosis Hepática Biliar , Análisis de la Aleatorización Mendeliana , Rosácea , Humanos , Rosácea/genética , Rosácea/epidemiología , Rosácea/diagnóstico , Colangitis Esclerosante/genética , Colangitis Esclerosante/epidemiología , Cirrosis Hepática Biliar/genética , Cirrosis Hepática Biliar/epidemiología , Cirrosis Hepática Biliar/diagnóstico , Cirrosis Hepática Biliar/inmunología , Hepatitis Autoinmune/genética , Hepatitis Autoinmune/epidemiología , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/inmunología , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/epidemiologíaRESUMEN
Background: Lung cancer is a highly prevalent cancer on a global scale and its oncogenic process is driven by the accumulation of multiple pathological events. Epigenetics has gained significant recognition in recent years as a crucial contributor to the development of lung cancer. Epigenetics include processes such as DNA methylation, histone modification, chromatin remodeling, and RNA modification. These pathways lead to enduring alterations in genetic phenotypes, which are crucial in the advancement and growth of lung cancer. However, the specific mechanisms and roles of epigenetics in lung cancer still need to be further elucidated. Methods: We obtained publications from the Web of Science databases and applied a rigorous search method to filter them. Ultimately, we gathered high-quality publications that had received the highest 100 number of citations. The data were processed and visualized by various bibliometric tools. Results: The 100 papers had varying numbers of citations, with the lowest being 491 and the most being 6316. On average, each work received 1119 citations. A total of 1056 co-authors were involved in publishing these papers in 59 journals from 185 institutions in 27 countries. The majority of high-caliber research in the subject of lung cancer epigenetics is conducted in advanced countries, with the United States taking the lead in terms of both the quantity of articles produced and their academic influence. The study of DNA methylation has been a longstanding research priority in the discipline. With the development of next-generation sequencing technology in recent years, research related to non-coding RNA has become a research hotspot. Future research directions may focus more on exploring the mechanisms of action of messenger RNA and circular RNA and developing targeted treatment strategies based on non-coding RNA drugs. Conclusion: We analyzed 100 top lung cancer and epigenetics documents through various bibliometric analysis tools. This study provides a concise overview of the findings from prior research, anticipates future research directions, and offers potential avenues for additional investigation.
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Mitochondria are essential organelles involved in various metabolic processes in eukaryotes. The imaging, targeting, and investigation of cell death mechanisms related to mitochondria have garnered significant interest. Small-molecule fluorescent probes have proven to be robust tools for utilizing light to advance the study of mitochondrial biology. In this study, we present the rational design of cationic Nile blue probes carrying a permanent positive charge for these purposes. The cationic Nile blue probes exhibit excellent mitochondrial permeability, unique solvatochromism, and resistance to oxidation. We observed weaker fluorescence in aqueous solutions compared to lipophilic solvents, thereby minimizing background fluorescence in the cytoplasm. Additionally, we achieved photoredox switching of the cationic Nile blue probes under mild conditions. This enabled us to demonstrate their application for the first time in single-molecule localization microscopy of mitochondria, allowing us to observe mitochondrial fission and fusion behaviors. Compared to conventional cyanine fluorophores, this class of dyes demonstrated prolonged resistance to photobleaching, likely due to their antioxidation properties. Furthermore, we extended the application of cationic Nile blue probes to the mitochondria-specific delivery of taxanes, facilitating the study of direct interactions between the drug and organelles. Our approach to triggering cell death without reliance on microtubule binding provides valuable insights into anticancer drug research and drug-resistance mechanisms.
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Gonadotropin-releasing hormone (GnRH) vaccines have been successfully used for the inhibition of gonadal development and function, but current GnRH-based vaccines often present variability in the response. Cross-reactive material 197 (CRM197) has been used as carrier molecules to enhance an immune response to associated antigens. So, the synthetic mammalian tandem-repeated GnRH hexamer (GnRH6) gene was integrated into the expression plasmid pET-21a. Recombinant GnRH6-CRM197 protein was subsequently overexpressed in Escherichia coli strain BL21 and purified through Nickel column affinity chromatography and the antigenicity and biological effects of GnRH6-CRM197 were evaluated in rats. Sixteen 4-month-old adult male rats were randomly divided into two groups: the GnRH6-CRM197 group (n = 8) and the control group (n = 8). The GnRH6-CRM197 group rats were subcutaneously immunized with 100 µg of GnRH6-CRM197, administered thrice at 2-week intervals with GnRH6-CRM197.The control group received only a white oil adjuvant. Following the initial immunization, the weights of animals were recorded, and blood samples were collected from the orbital sinus at 4, 4.5, 5, 5.5, 6, 6.5, and 7 months. Serum antibody titers and testosterone concentrations were quantified using ELISA and CLIA, respectively. Additionally, testicular tissues were collected for morphological examination. The results revealed a significant increase in serum GnRH antibody titers (p < 0.05), but a significant decrease in serum testosterone concentrations (p < 0.05), and the weight, length, width, and girth of the testis, and the number of spermatogonia cells, spermatocytes, and sperm cells in the immunized rats. Furthermore, seminiferous tubules revealed significant atrophy and no sperm were observed in the immunized animals. Thus, GnRH6-CRM197 may be an effective antigen and a potential immunocastration vaccine.
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Hormona Liberadora de Gonadotropina , Animales , Masculino , Hormona Liberadora de Gonadotropina/inmunología , Ratas , Testículo/efectos de los fármacos , Testosterona/sangre , Ratas Sprague-Dawley , InmunizaciónRESUMEN
Identity recognition as the first barrier of intelligent security plays a vital role, which is facing new challenges that are unable to meet the need of intelligent era due to low accuracy, complex configuration and dependence on power supply. Here, a finger temperature-driven intelligent identity recognition strategy is presented based on a thermogalvanic hydrogel (TGH) by actively discerning biometric characteristics of fingers. The TGH is a dual network PVA/Agar hydrogel in an H2O/glycerol binary solvent with [Fe(CN)6]3-/4- as a redox couple. Using a concave-arranged TGH array, the characteristics of users can be distinguished adequately even under an open environment by extracting self-existent intrinsic temperature features from five typical sites of fingers. Combined with machine learning, the TGH array can recognize different users with a high average accuracy of 97.6%. This self-powered identity recognition strategy is further applied to a smart lock, attaining a more reliable security protection from biometric characteristics than bare passwords. This work provides a promising solution for achieving better identity recognition, which has great advantages in intelligent security and human-machine interaction toward future Internet of everything.
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Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) play key roles in regulating testosterone secretion and spermatogenesis in male mammals, respectively, and they maintain the fertility of male animals by binding to their corresponding receptors. We designed and prepared a recombinant LH receptor (LHR) subunit vaccine and a recombinant FSH receptor (FSHR) subunit vaccine and used male Sprague Dawley (SD) rats as a model to examine their effects on testicular development, spermatogenesis, and testosterone secretion in prepubertal and pubertal mammals. Both vaccines (LHR-DTT and FSHR-DTT) significantly decreased the serum testosterone level in prepubertal rats (p < 0.05) but had no effect on the testosterone secretion in pubertal rats; both vaccines decreased the number of cell layers in the seminiferous tubules and reduced spermatogenesis in prepubertal and pubertal rats. Subunit vaccine FSHR-DTT decreased the sperm density in the epididymis in both prepubertal and pubertal rats (p < 0.01) and lowered testicular index and sperm motility in pubertal rats (p < 0.05), whereas LHR-DTT only reduced the sperm density in the epididymis in pubertal rats (p < 0.05). These results indicate that the FSHR subunit vaccine may be a promising approach for immunocastration, but it still needs improvements in effectiveness.
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Puberty is considered a prerequisite for affecting reproductive performance and productivity. Little was known about molecular changes in pubertal goat ovaries. Therefore, we measured and performed a correlation analysis of the mRNA and proteins changes in the pre-pubertal and pubertal goat ovaries. The results showed that only six differentially expressed genes and differentially abundant proteins out of 18,139 genes and 7550 proteins quantified had significant correlations. CNTN2 and THBS1, discovered in the mRNA-mRNA interaction network, probably participated in pubertal and reproductive regulation by influencing GnRH receptor signals, follicular development, and ovulation. The predicted core transcription factors may either promote or inhibit the expression of reproductive genes and act synergistically to maintain normal reproductive function in animals. The interaction between PKM and TIMP3 with other proteins may impact animal puberty through energy metabolism and ovarian hormone secretion. Pathway enrichment analyses revealed that the co-associated key pathways between ovarian genes and proteins at puberty included calcium signalling pathway and olfactory transduction. These pathways were associated with gonadotropin-releasing hormone synthesis and secretion, signal transmission, and cell proliferation. In summary, these results enriched the potential molecules and signalling pathways that affect puberty and provided new insights for regulating and promoting the onset of puberty. SIGNIFICANCE: This study conducted the first transcriptomic and proteomic correlation analysis of pre-pubertal and pubertal goat ovaries and identified six significantly correlated molecules at both the gene and protein levels. Meanwhile, we were drawn to several molecules and signalling pathways that may play a regulatory role in the onset of puberty and reproduction by influencing reproductive-related gene expression, GnRH receptor signals, energy metabolism, ovarian hormone secretion, follicular development, and ovulation. This information contributed to identify potential biomarkers in pubertal goat ovaries, which was vital for predicting the onset of puberty and improving livestock performance.
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Cabras , Ovario , Proteómica , Maduración Sexual , Animales , Femenino , Cabras/genética , Maduración Sexual/fisiología , Ovario/metabolismo , Proteómica/métodos , Perfilación de la Expresión Génica , TranscriptomaRESUMEN
The study aimed to investigate the effect of Grid1, encoding the glutamate ionotropic receptor delta type subunit 1 (GluD1), on puberty onset in female rats. Grid1 mRNA and protein expression was detected in the hypothalamus of female rats at prepuberty and puberty. The levels of Grid1 mRNA in the hypothalamus, the fluorescence intensity in the arcuate nucleus and paraventricular nucleus of the prepubertal rats was significantly lower than pubertal. Additionally, the expression of Grid1 was suppressed in primary hypothalamus cells and prepubertal rat. Finally, investigated the effect of Grid1 knockdown on puberty onset and reproductive performance. Treatment of hypothalamic neurons with LV-Grid1 decreased the level of Grid1 and Rfrp-3 (encoding RFamide-related peptide 3) mRNA expression, but increased the Gnrh (encoding gonadotropin-releasing hormone) mRNA levels. After an ICV injection, the time for the rat vaginal opening occurred earlier. Moreover, Gnrh mRNA expression was increased, whereas Rfrp-3 mRNA expression was decreased in the hypothalamus. The concentration of progesterone (P4) in the serum was significantly decreased compare with control group. Ovary hematoxylin-eosin staining revealed that the LV-Grid1 group mainly contained primary and secondary follicles. The reproductive performance of the rats was not affected by the Grid1 knockdown. Therefore, Grid1 may aï¬ect the onset of puberty in female rats by regulating the levels of Gnrh, and Rfrp-3 in the hypothalamus, as well as the concentrations of P4, but not reproduction performance.
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Hormona Liberadora de Gonadotropina , Hormonas Hipotalámicas , Hipotálamo , Maduración Sexual , Animales , Femenino , Ratas , Hormona Liberadora de Gonadotropina/metabolismo , Hormona Liberadora de Gonadotropina/genética , Hipotálamo/metabolismo , Neuronas/metabolismo , Neuropéptidos/metabolismo , Neuropéptidos/genética , Progesterona/sangre , Progesterona/metabolismo , Ratas Sprague-Dawley , ARN Mensajero/metabolismo , ARN Mensajero/genética , Maduración Sexual/fisiologíaRESUMEN
Copper oxides nanoparticles (CuO NPs) are widely used for a variety of industrial and life science applications. In addition to cause neurotoxicity, hepatotoxicity, immunotoxicity, CuO NPs have also been reported to adversely affect the reproductive system in animals; However, little is known about the effects and potential mechanism of CuO NPs exposure on oocyte quality, especially oocyte maturation. In the present study, we reported that CuO NPs exposure impairs the oocyte maturation by disrupting meiotic spindle assembly and chromosome alignment, as well as kinetochore-microtubule attachment. In addition, CuO NPs exposure also affects the acetylation level of α-tubulin in mice oocyte, which hence impairs microtubule dynamics and organization. Besides, CuO NPs exposure would result in the mis-localization of Juno and Ovastacin, which might be one of the critical factors leading to the failure of oocyte maturation. Finally, CuO NPs exposure impairs the mitochondrial distribution and induced high levels of ROS, which led to the accumulation of DNA damage and occurrence of apoptosis. In summary, our results indicated that CuO NPs exposure had potential toxic effects on female fertility and led to the poor oocyte quality in female mice.
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Nanopartículas del Metal , Enfermedades Mitocondriales , Nanopartículas , Femenino , Ratones , Animales , Cobre/farmacología , Especies Reactivas de Oxígeno/metabolismo , Estrés Oxidativo , Oocitos , Meiosis , Óxidos , Nanopartículas del Metal/toxicidadRESUMEN
BACKGROUND: Pregnancy toxemia is a common disease, which occurs in older does that are pregnant with multiple lambs in the third trimester. Most of the sick goats die within a few days, which can seriously impact the economic benefits of goat breeding enterprises. The disease is believed to be caused by malnutrition, stress, and other factors, that lead to the disorder of lipid metabolism, resulting in increased ketone content, ketosis, ketonuria, and neurological symptoms. However, the changes in gut microbes and their metabolism in this disease are still unclear. The objective of this experiment was to evaluate the effect of toxemia of pregnancy on the fecal microbiome and metabolomics of does. RESULTS: Eight pregnant does suspected of having toxemia of pregnancy (PT group) and eight healthy does during the same pregnancy (NC group) were selected. Clinical symptoms and pathological changes at necropsy were observed, and liver tissue samples were collected for pathological sections. Jugular venous blood was collected before morning feeding to detect biochemical indexes. Autopsy revealed that the liver of the pregnancy toxemia goat was enlarged and earthy yellow, and the biochemical results showed that the serum levels of aspartate aminotransferase (AST) and ß-hydroxybutyric acid (B-HB) in the PT group were significantly increased, while calcium (Ca) levels were significantly reduced. Sections showed extensive vacuoles in liver tissue sections. The microbiome analysis found that the richness and diversity of the PT microbiota were significantly reduced. Metabolomic analysis showed that 125 differential metabolites were screened in positive ion mode and enriched in 12 metabolic pathways. In negative ion mode, 100 differential metabolites were screened and enriched in 7 metabolic pathways. CONCLUSIONS: Evidence has shown that the occurrence of pregnancy toxemia is related to gut microbiota, and further studies are needed to investigate its pathogenesis and provide research basis for future preventive measures of this disease.
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Enfermedades de las Cabras , Microbiota , Preeclampsia , Enfermedades de las Ovejas , Toxemia , Femenino , Embarazo , Ovinos , Animales , Preeclampsia/veterinaria , Cabras/metabolismo , Toxemia/veterinaria , Metaboloma , Metabolómica , Oveja Doméstica/metabolismo , ARN Ribosómico 16SRESUMEN
Prothioconazole (PTC), a novel broad-spectrum triazole fungicide, has attracted widespread concern due to its wide use and toxicological effects on non-target organisms. However, little is known about the impact of PTC on oocyte quality and female fertility, especially on oocyte maturation and fertilization. In the present study, we reported that PTC exposure affects the oocyte developmental competence and oocyte fertilization ability to weaken female fertility. Firstly, PTC compromises oocyte development ability by disrupting spindle morphology and chromosome alignment, as well as decreasing acetylation level of α-tubulin and disrupting kinetochore-microtubule attachments. In addition, PTC compromises oocyte fertilization ability by weakening the sperm binding ability and impairing the dynamics of Juno, Cortical granule and Ovastacin. Finally, single-cell transcriptome analysis revealed that PTC exposure has potentially toxic effects on oocyte development and fertilization, which is caused by the mitochondrial dysfunction and the occurrence of oxidative stress and apoptosis. In summary, our results indicated that PTC exposure had potentially toxic effects on female fertility and led to poor oocyte quality in female mice.
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Enfermedades Mitocondriales , Semen , Masculino , Femenino , Ratones , Animales , Oocitos/metabolismo , Triazoles , Estrés Oxidativo , Fertilización , Apoptosis , Enfermedades Mitocondriales/metabolismoRESUMEN
OBJECTIVE: To evaluate the blood pressure (BP) lowering ability of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), in individuals with type-2 diabetes (T2D). METHODS: Randomized controlled trials (RCTs) comparing subcutaneous or oral semaglutide with placebo or other antihyperglycemic agents (AHAs) in T2D patients were identified by searching PubMed, Embase, Web of Science, ClinicalTrials.gov and Cochrane Library. These screened studies included the outcomes of interest: systolic and/or diastolic BP. Weighted mean differences (WMDs) and 95 % confidence intervals (CIs) were used to present the meta-analysis results. Pooled and sensitivity analyses were performed, and the risk of bias was evaluated. RESULTS: Twenty-nine RCTs with a total of 26985 participants were recruited in the final analysis. The WMD in change from baseline in systolic BP (SBP) of semaglutide versus placebo or other AHAs was -2.31 mmHg (95% CI: -3.11 to -1.51), while that for diastolic BP (DBP) was 0.09 mmHg (95% CI: -0.16 to 0.33). It also reduced glycated hemoglobin A1c (HbA1c) by 0.75% (95% CI: -0.92 to -0.58) and body weight loss by 2.80 kg (95% CI: -3.51 to -2.08). The reduction in SBP was similar for subcutaneous and oral administration of semaglutide, with -2.36 (95% CI: -3.38 to -1.35) and -2.50 (95% CI: -3.48 to -1.53), respectively. CONCLUSIONS: In T2D, SBP decreased significantly in the semaglutide group compared with placebo or other active controls. According to the efficacy results from this meta-analysis, subcutaneous and oral semaglutide have similar SBP-reducing effects. Therefore, the treatment of T2D patients with subcutaneous semaglutide or oral preparations is beneficial for reducing SBP.
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Diabetes Mellitus Tipo 2 , Humanos , Presión Sanguínea , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Péptidos Similares al Glucagón/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Puberty marks the end of childhood and achieve sexual maturation and fertility. The role of hypothalamic proteins in regulating puberty onset is unclear. We performed a comprehensive differential proteomics and phosphoproteomics analysis in prepubertal and pubertal goats to determine the roles of hypothalamic proteins and phosphoproteins during the onset of puberty. RESULTS: We used peptide and posttranslational modifications peptide quantification and statistical analyses, and identified 69 differentially expressed proteins from 5,057 proteins and 576 differentially expressed phosphopeptides from 1574 phosphorylated proteins. Combined proteomic and phosphoproteomics, 759 correlated proteins were identified, of which 5 were differentially expressed only at the protein level, and 201 were only differentially expressed at the phosphoprotein level. Pathway enrichment analyses revealed that the majority of correlated proteins were associated with glycolysis/gluconeogenesis, Fc gamma R-mediated phagocytosis, focal adhesion, GABAergic synapse, and Rap1 signaling pathway. These pathways are related to cell proliferation, neurocyte migration, and promoting the release of gonadotropin-releasing hormone in the hypothalamus. CTNNB1 occupied important locations in the protein-protein interaction network and is involved in focal adhesion. CONCLUSION: The results demonstrate that the proteins differentially expression only at the protein level or only differentially expressed at the phosphoprotein level and their related signalling pathways are crucial in regulating puberty in goats. These differentially expressed proteins and phosphorylated proteins may constitute the proteomic backgrounds between the two different stages.
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Cabras , Proteómica , Animales , Femenino , Humanos , Cabras/metabolismo , Hipotálamo/metabolismo , Pubertad , Maduración Sexual/fisiología , Hormona Liberadora de Gonadotropina/metabolismo , Fosfoproteínas/metabolismoRESUMEN
Maternal age at childbearing has continued to increase in recent decades. However, whether and how it influences offspring adult traits are largely unknown. Here, using adult body size as the primary readout, we reveal that maternal rather than paternal age has an evolutionarily conserved effect on offspring adult traits in humans, Drosophila, and Caenorhabditis elegans. Elucidating the mechanisms of such effects in humans and other long-lived animals remains challenging due to their long life course and difficulties in conducting in vivo studies. We thus employ the short-lived and genetically tractable nematode C. elegans to explore the mechanisms underlying the regulation of offspring adult trait by maternal aging. By microscopic analysis, we find that old worms transmit aged mitochondria with a donut-like shape to offspring. These mitochondria are rejuvenated in the offspring's early life, with their morphology fully restored before adulthood in an AMPK-dependent manner. Mechanistically, we demonstrate that early-life mitochondrial dysfunction activates AMPK, which in turn not only alleviates mitochondrial abnormalities but also activates TGFß signaling to increase offspring adult size. Together, our findings provide mechanistic insight into the ancient role of maternal aging in shaping the traits of adult offspring.
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Proteínas Quinasas Activadas por AMP , Caenorhabditis elegans , Animales , Humanos , Adulto , Anciano , Envejecimiento/fisiología , Tamaño Corporal , MitocondriasRESUMEN
This study investigated how lncRNA Meg3 affects the onset of puberty in female rats. We determined Meg3 expression in the hypothalamus-pituitary-ovary axis of female rats at the infancy, prepubertal, pubertal, and adult life stages, using quantitative reverse transcription polymerase chain reaction (qRT-PCR). We also assessed the effects of Meg3 knockdown on the expression levels of puberty-related genes and Wnt/ß-catenin proteins in the hypothalamus, time of puberty onset, levels of reproductive genes and hormones, and ovarian morphology in female rats. Meg3 expression in the ovary varied significantly between prepuberty and puberty (P < 0.01). Meg3 knockdown decreased the expression of Gnrh, and Kiss1 mRNA (P < 0.05) and increased the expression of Wnt (P < 0.01) and ß-catenin proteins (P < 0.05) in the hypothalamic cells. Onset of puberty in Meg3 knockdown rats was delayed compared to the control group (P < 0.05). Meg3 knockdown decreased Gnrh mRNA levels (P < 0.05) and increased Rfrp-3 mRNA levels (P < 0.05) in the hypothalamus. The serum concentrations of progesterone (P4) and estradiol (E2) of Meg3 knockdown rats were lower than those in the control animals (P < 0.05). Higher longitudinal diameter and ovary weight were found in Meg3 knockdown rats (P < 0.05). These findings suggest that Meg3 regulates the expression of Gnrh, Kiss-1 mRNA and Wnt/ß-catenin proteins in the hypothalamic cells, and Gnrh, Rfrp-3 mRNA of the hypothalamus and the serum concentration of P4 and E2, and its knockdown delays the onset of puberty in female rats.
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ARN Largo no Codificante , Ratas , Femenino , Animales , ARN Largo no Codificante/metabolismo , Ratas Sprague-Dawley , Hormona Liberadora de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Kisspeptinas/metabolismo , Maduración Sexual/fisiología , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: Age at puberty is an important factor affecting goat fertility, with endocrine and genetic factors playing a crucial role in the onset of puberty. To better understand the relationship between endocrine and genetic factors and mechanisms underlying puberty onset in goats, reproductive hormone levels were analyzed by ELISA and ultraperformance liquid chromatography-multiple reaction monitoring-multistage/mass spectrometry and RNA sequencing was performed to analyze ovarian genes. RESULTS: Serum follicle stimulating hormone, luteinizing hormone, estradiol, 11-deoxycortisol, 11-deoxycorticosterone, corticosterone, cortisone, and cortisol levels were found to be higher but progesterone were lower in pubertal goats as compared to those in prepubertal goats (P < 0.05). A total of 18,139 genes were identified in cDNA libraries, and 75 differentially expressed genes (DEGs) were identified (|log2 fold change|≥ 1, P ≤ 0.05), of which 32 were significantly up- and 43 were down-regulated in pubertal goats. Gene ontology enrichment analyses indicated that DEGs were mainly involved in "metabolic process," "signaling," "reproduction," and "growth." Further, DEGs were significantly enriched in 91 Kyoto Encyclopedia of Genes and Genomes pathways, including estrogen signaling pathway, steroid hormone biosynthesis, and cAMP signaling pathway. Bioinformatics analysis showed that PRLR and THBS1 were highly expressed in pubertal ovaries, and ZP3, ZP4, and ASTL showed low expression, suggesting their involvement in follicular development and lutealization. CONCLUSIONS: To summarize, serum hormone changes and ovarian DEGs expression were investigated in our study. Further studies are warranted to comprehensively explore the functions of DEGs in goat puberty.
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Cabras , Ovario , Animales , Femenino , Ovario/metabolismo , Cabras/genética , Hormona Luteinizante , Hormona Folículo Estimulante , Estradiol , Perfilación de la Expresión GénicaRESUMEN
MicroRNA21 (MIR21) abundance in porcine oocytes and cumulus cells increases during in vitro maturation. The mechanism by which MIR21 regulates oocyte maturation and the effect on the developmental competence of subsequent embryos remains unclear. The objective of this study was to assess the function of MIR21 during porcine oocyte maturation and its effect on embryonic development. Treatment with peptide nucleic acid MIR21 inhibitor (MIR21-PNA), designed to specifically bind to and prevent MIR21 activity during in vitro oocyte maturation, decreased cumulus cell expansion, and the oocyte ability to achieve metaphase II maturation stage when compared to control groups. Following parthenogenetic activation, the cleavage rate at 48 h in the MIR21-PNA group was decreased (p ≤ 0.03) relative to the control groups. Additionally, liquid chromatography-mass spectrometry (LC-MS/MS) of oocyte and cumulus cell total protein following MIR21-PNA treatment during in vitro maturation identified changes in signaling pathways with primary involvement of glucose metabolism (GM) pathways. Furthermore, there was no difference (p = 0.21) in oocyte maturation of control and MIR21-PNA treated oocytes when cultured in pyruvate lacking medium. Finally, MIR21-PNA treatment decreased (p = 0.04) glutathione and increased (p = 0.07) reactive oxygen species production in the oocyte. These data suggest that MIR21 influences porcine oocyte maturation by regulating GM pathways in the cumulus-oocyte complex.
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Ácidos Nucleicos de Péptidos , Embarazo , Femenino , Porcinos , Animales , Especies Reactivas de Oxígeno/metabolismo , Ácidos Nucleicos de Péptidos/metabolismo , Ácidos Nucleicos de Péptidos/farmacología , Cromatografía Liquida , Espectrometría de Masas en Tándem , Técnicas de Maduración In Vitro de los Oocitos/métodos , Células del Cúmulo/metabolismo , Oocitos/metabolismo , Desarrollo Embrionario , Glutatión/metabolismo , Glucosa/farmacología , Glucosa/metabolismo , Redes y Vías Metabólicas , Piruvatos/metabolismo , Piruvatos/farmacologíaRESUMEN
BACKGROUND: Changes in the abundance of ovarian proteins play a key role in the regulation of reproduction. However, to date, no studies have investigated such changes in pubescent goats. Herein we applied isobaric tags for relative and absolute quantitation (iTRAQ) and liquid chromatography-tandem mass spectrometry to analyze the expression levels of ovarian proteins in pre-pubertal (n = 3) and pubertal (n = 3) goats. RESULTS: Overall, 7,550 proteins were recognized; 301 (176 up- and 125 downregulated) were identified as differentially abundant proteins (DAPs). Five DAPs were randomly selected for expression level validation by Western blotting; the results of Western blotting and iTRAQ analysis were consistent. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that DAPs were enriched in olfactory transduction, glutathione metabolism, and calcium signaling pathways. Besides, gene ontology functional enrichment analysis revealed that several DAPs enriched in biological processes were associated with cellular process, biological regulation, metabolic process, and response to stimulus. Protein-protein interaction network showed that proteins interacting with CDK1, HSPA1A, and UCK2 were the most abundant. CONCLUSIONS: We identified 301 DAPs, which were enriched in olfactory transduction, glutathione metabolism, and calcium signaling pathways, suggesting the involvement of these processes in the onset of puberty. Further studies are warranted to more comprehensively explore the function of the identified DAPs and aforementioned signaling pathways to gain novel, deeper insights into the mechanisms underlying the onset of puberty.
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Cabras , Proteómica , Animales , Femenino , Glutatión , Ovario , Proteómica/métodos , Maduración SexualRESUMEN
Insulin-like growth factor-binding protein-5 (IGFBP-5) has recently been shown to alter the reproductive capacity by regulating insulin-like growth factor (IGF) bioavailability or IGF-independent effects. The present study aimed to investigate the effect and mechanism of IGFBP-5 on the onset of puberty in female rats. Immunofluorescence and real-time quantitative PCR were used to determine the expression and location of IGFBP-5 mRNA and protein distribution in the infant's hypothalamus-pituitary-ovary (HPO) axis prepuberty, peripuberty, puberty and adult female rats. Prepubertal rats with IGFBP-5 intracerebroventricular (ICV) were injected to determine the puberty-related genes expression and the concentrations of reproductive hormones. Primary hypothalamic cells were treated with IGFBP-5 to determine the expression of puberty-related genes and the Akt and mTOR proteins. Results showed that Igfbp-5 mRNA and protein were present on the HPO axis. The addition of IGFBP-5 to primary hypothalamic cells inhibited the expression of Gnrh and Igf-1 mRNAs (P < 0.05) and increased the expression of AKT and mTOR protein (P < 0.01). IGFBP-5 ICV-injection delayed the onset of puberty, reduced Gnrh, Igf-1, and Fshß mRNAs, and decreased the concentrations of E2, P4, FSH,serum LH levels and the ovaries weight (P < 0.05). More corpus luteum and fewer primary follicles were found after IGFBP-5 injection (P < 0.05).