RESUMEN
Plants frequently encounter wounding and have evolved an extraordinary regenerative capacity to heal the wounds. However, the wound signal that triggers regenerative responses has not been identified. Here, through characterization of a tomato mutant defective in both wound-induced defense and regeneration, we demonstrate that in tomato, a plant elicitor peptide (Pep), REGENERATION FACTOR1 (REF1), acts as a systemin-independent local wound signal that primarily regulates local defense responses and regenerative responses in response to wounding. We further identified PEPR1/2 ORTHOLOG RECEPTOR-LIKE KINASE1 (PORK1) as the receptor perceiving REF1 signal for plant regeneration. REF1-PORK1-mediated signaling promotes regeneration via activating WOUND-INDUCED DEDIFFERENTIATION 1 (WIND1), a master regulator of wound-induced cellular reprogramming in plants. Thus, REF1-PORK1 signaling represents a conserved phytocytokine pathway to initiate, amplify, and stabilize a signaling cascade that orchestrates wound-triggered organ regeneration. Application of REF1 provides a simple method to boost the regeneration and transformation efficiency of recalcitrant crops.
Asunto(s)
Proteínas de Plantas , Regeneración , Transducción de Señal , Solanum lycopersicum , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Solanum lycopersicum/metabolismo , Regulación de la Expresión Génica de las Plantas , Péptidos/metabolismoRESUMEN
Flowering plants have evolved numerous intraspecific and interspecific prezygotic reproductive barriers to prevent production of unfavourable offspring1. Within a species, self-incompatibility (SI) is a widely utilized mechanism that rejects self-pollen2,3 to avoid inbreeding depression. Interspecific barriers restrain breeding between species and often follow the SI × self-compatible (SC) rule, that is, interspecific pollen is unilaterally incompatible (UI) on SI pistils but unilaterally compatible (UC) on SC pistils1,4-6. The molecular mechanisms underlying SI, UI, SC and UC and their interconnections in the Brassicaceae remain unclear. Here we demonstrate that the SI pollen determinant S-locus cysteine-rich protein/S-locus protein 11 (SCR/SP11)2,3 or a signal from UI pollen binds to the SI female determinant S-locus receptor kinase (SRK)2,3, recruits FERONIA (FER)7-9 and activates FER-mediated reactive oxygen species production in SI stigmas10,11 to reject incompatible pollen. For compatible responses, diverged pollen coat protein B-class12-14 from SC and UC pollen differentially trigger nitric oxide, nitrosate FER to suppress reactive oxygen species in SC stigmas to facilitate pollen growth in an intraspecies-preferential manner, maintaining species integrity. Our results show that SRK and FER integrate mechanisms underlying intraspecific and interspecific barriers and offer paths to achieve distant breeding in Brassicaceae crops.
Asunto(s)
Brassicaceae , Flores , Hibridación Genética , Proteínas de Plantas , Polinización , Brassicaceae/genética , Brassicaceae/metabolismo , Depresión Endogámica , Óxido Nítrico/metabolismo , Fosfotransferasas/metabolismo , Fitomejoramiento , Proteínas de Plantas/metabolismo , Polen/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Especificidad de la Especie , Flores/metabolismo , AutofecundaciónRESUMEN
Carotenoids perform a broad range of important functions in humans; therefore, carotenoid biofortification of maize (Zea mays L.), one of the most highly produced cereal crops worldwide, would have a global impact on human health. PLASTID TERMINAL OXIDASE (PTOX) genes play an important role in carotenoid metabolism; however, the possible function of PTOX in carotenoid biosynthesis in maize has not yet been explored. In this study, we characterized the maize PTOX locus by forward- and reverse-genetic analyses. While most higher plant species possess a single copy of the PTOX gene, maize carries two tandemly duplicated copies. Characterization of mutants revealed that disruption of either copy resulted in a carotenoid-deficient phenotype. We identified mutations in the PTOX genes as being causal of the classic maize mutant, albescent1. Remarkably, overexpression of ZmPTOX1 significantly improved the content of carotenoids, especially ß-carotene (provitamin A), which was increased by ~threefold, in maize kernels. Overall, our study shows that maize PTOX locus plays an important role in carotenoid biosynthesis in maize kernels and suggests that fine-tuning the expression of this gene could improve the nutritional value of cereal grains.
Asunto(s)
Oxidorreductasas , Zea mays , Humanos , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , Zea mays/genética , Zea mays/metabolismo , Carotenoides/metabolismo , beta Caroteno/metabolismo , Grano Comestible/genética , Grano Comestible/metabolismo , Plastidios/genética , Plastidios/metabolismoRESUMEN
Several different mutations in the proteome of centriole 1 centriolar protein B (POC1B) have been linked to cone dystrophy or cone-rod dystrophy (CORD). However, mutations in POC1B that are associated with both CORD and oligoasthenoteratozoospermia (OAT) have not been reported previously. Here, whole-exome sequencing was performed to identify a homozygous frameshift variant (c.151delG) in POC1B in the two brothers who had been diagnosed with both CORD and OAT from a consanguineous family. Transcript and protein analyses of biological samples from the two patients carrying the variant showed that POC1B protein is lost in sperm cells. The system CRISPR/Cas9 was utilized to create poc1bc.151delG/c.151delG knock-in (KI) mice. Notably, poc1bc.151delG/c.151delG KI male mice presented with OAT phenotype. Additionally, testicular histology and transmission electron microscopy analysis of the testes and sperm indicated that Poc1b mutation results in abnormal formation of acrosomes and flagella. Collectively, according to our experimental data on human volunteers and animal models, biallelic mutations in POC1B can cause OAT and CORD in mice and humans.
Asunto(s)
Astenozoospermia , Distrofias de Conos y Bastones , Infertilidad Masculina , Oligospermia , Humanos , Masculino , Animales , Ratones , Oligospermia/genética , Infertilidad Masculina/genética , Astenozoospermia/genética , Semen/metabolismo , Mutación , Proteínas de Ciclo Celular/genéticaRESUMEN
The phytohormone auxin controls plant growth and development via TIR1-dependent protein degradation of canonical AUX/IAA proteins, which normally repress the activity of auxin response transcription factors (ARFs). IAA33 is a non-canonical AUX/IAA protein lacking a TIR1-binding domain, and its role in auxin signaling and plant development is not well understood. Here, we show that IAA33 maintains root distal stem cell identity and negatively regulates auxin signaling by interacting with ARF10 and ARF16. IAA33 competes with the canonical AUX/IAA repressor IAA5 for binding to ARF10/16 to protect them from IAA5-mediated inhibition. In contrast to auxin-dependent degradation of canonical AUX/IAA proteins, auxin stabilizes IAA33 protein via MITOGEN-ACTIVATED PROTEIN KINASE 14 (MPK14) and does not affect IAA33 gene expression. Taken together, this study provides insight into the molecular functions of non-canonical AUX/IAA proteins in auxin signaling transduction.
Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Ácidos Indolacéticos/farmacología , Proteínas Nucleares/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Arabidopsis/efectos de los fármacos , Arabidopsis/crecimiento & desarrollo , Proteínas de Arabidopsis/genética , Proteínas de Unión al ADN/genética , Proteínas Nucleares/genética , Fosforilación , Reguladores del Crecimiento de las Plantas/farmacología , Plantas Modificadas Genéticamente/efectos de los fármacos , Plantas Modificadas Genéticamente/crecimiento & desarrollo , Proteolisis , Transducción de SeñalRESUMEN
BACKGROUND: Prostate cancer is one of the most common cancers in men with a significant proportion of patients developing biochemical recurrence (BCR) after treatment. Programmed cell death (PCD) mechanisms are known to play critical roles in tumor progression and can potentially serve as prognostic and therapeutic biomarkers in PCa. This study aimed to develop a prognostic signature for BCR in PCa using PCD-related genes. MATERIALS AND METHODS: We conducted an analysis of 19 different modes of PCD to develop a comprehensive model. Bulk transcriptomic, single-cell transcriptomic, genomic, and clinical data were collected from multiple cohorts, including TCGA-PRAD, GSE58812, METABRIC, GSE21653, and GSE193337. We analyzed the expression and mutations of the 19 PCD modes and constructed, evaluated, and validated the model. RESULTS: Ten PCD modes were found to be associated with BCR in PCa, with specific PCD patterns exhibited by various cell components within the tumor microenvironment. Through Lasso Cox regression analysis, we established a Programmed Cell Death Index (PCDI) utilizing an 11-gene signature. High PCDI values were validated in five independent datasets and were found to be associated with an increased risk of BCR in PCa patients. Notably, older age and advanced T and N staging were associated with higher PCDI values. By combining PCDI with T staging, we constructed a nomogram with enhanced predictive performance. Additionally, high PCDI values were significantly correlated with decreased drug sensitivity, including drugs such as Docetaxel and Methotrexate. Patients with lower PCDI values demonstrated higher immunophenoscores (IPS), suggesting a potentially higher response rate to immune therapy. Furthermore, PCDI was associated with immune checkpoint genes and key components of the tumor microenvironment, including macrophages, T cells, and NK cells. Finally, clinical specimens validated the differential expression of PCDI-related PCDRGs at both the gene and protein levels. CONCLUSION: In conclusion, we developed a novel PCD-based prognostic feature that successfully predicted BCR in PCa patients and provided insights into drug sensitivity and potential response to immune therapy. These findings have significant clinical implications for the treatment of PCa.
RESUMEN
OBJECTIVES: To evaluate the efficacy of a novel approach to achieve the optimal penile erection during the penile doppler ultrasound (PDU) examination, which was oral sildenafil combined alprostadil injection. MATERIALS AND METHODS: A total of 60 ED patients were enrolled in our prospective study, and they were randomly assigned to two group with different PDU order. The approaches assisted the PDU included two models, mode A meaning injection of 15 µg alprostadil and model B meaning oral sildenafil 100 mg plus injection of 15 µg alprostadil. The PDU parameters were measured continuously before induced erection, and 5, 10, 15, 20, 25 min. RESULTS: Each group included 30 ED patients with similar clinical characteristics. After pooling the results together, the PSV, EDV, and RI were all improved significantly, when adding the oral sildenafil administration to assist PDU. Also, the clinical response of oral sildenafil administration plus alprostadil injection was better than that in alprostadil injection alone (p = 0.016). The arterial ED were decreased from 31.67% to 15.00% with the P value 0.031, and the mixed ED was also decreased statistically (23.33% vs 8.33%, p = 0.024). CONCLUSION: Oral sildenafil administration plus alprostadil injection could improve the diagnostic accuracy of PDU.
Asunto(s)
Disfunción Eréctil , Erección Peniana , Masculino , Humanos , Citrato de Sildenafil/farmacología , Erección Peniana/fisiología , Alprostadil , Disfunción Eréctil/tratamiento farmacológico , Disfunción Eréctil/diagnóstico , Estudios Prospectivos , Pene/diagnóstico por imagen , Ultrasonografía DopplerRESUMEN
BACKGROUND: Previous research has shown that testosterone deficiency (TD) increases the risk of anemia, but it is unclear whether anemia affects testosterone levels. This study investigated the influence of anemia on testosterone levels. METHODS: Utilizing data from six NHANES cycles, including demographic, testosterone levels, and hemoglobin concentrations, we employed multivariable-adjusted logistic regression to investigate the relationship between anemia and testosterone levels. Moreover, a two-sample Mendelian randomization (MR) study employing genome-wide association study (GWAS) data examined the causal relationship. Kaplan-Meier survival estimation was used to compared the overall survival (OS) of anemic and nonanemic patients with low testosterone and normal testosterone levels. RESULTS: The inclusion of 21,786 participants (2318 with anemia and19,468 without anemia) revealed that nonanemic patients exhibited higher testosterone levels than did anemic patients (ß = 22.616, 95% CI: 3.873-41.359, p = 0.01807). MR analysis confirmed anemia as a cause of TD (OR = 1.045, 95% CI: 1.020-1.071, p < 0.001). Anemic males with low testosterone had reduced OS compared to those with normal levels (p < 0.001). CONCLUSIONS: Anemia emerged as a potential risk factor for TD, highlighting a bidirectional relationship between these conditions. Additional prospective investigations are essential for the validation and reinforcement of our findings.
Asunto(s)
Anemia , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Encuestas Nutricionales , Testosterona , Humanos , Testosterona/sangre , Testosterona/deficiencia , Masculino , Anemia/genética , Anemia/epidemiología , Persona de Mediana Edad , Adulto , Anciano , Factores de RiesgoRESUMEN
OBJECTIVE: Shift work and Shift Work Sleep Disorder (SWSD) are known to affect the secretion of several neurotransmitters and hormones associated with premature ejaculation (PE). However, their specific influence on the regulation of male ejaculation remains unclear. This study explores the relationship between shift work, SWSD, and PE. METHODS: From April to October 2023, a cross-sectional survey was conducted across five regions of China to explore the work schedules, sleep quality, and sexual function of male workers. Participants' sleep quality was evaluated using a validated SWSD questionnaire, and their erectile function and ejaculatory control were assessed with the International Inventory of Erectile Function (IIEF-5) scores and Premature Ejaculation Diagnostic Tool (PEDT) scores, respectively. Univariate and multivariate linear regression analyses were employed to identify risk factors associated with PE. Confounders were controlled using multiple regression models, and clinical prediction models were developed to predict PE onset and assess the contribution of risk factors. RESULTS: The study included 1239 eligible participants, comprising 840 non-shift workers and 399 shift workers (148 with SWSD and 251 without SWSD). Compared to non-shift working males, those involved in shift work (ß 1.58, 95% CI 0.75 - 2.42, p < 0.001) and those suffering from SWSD (ß 2.86, 95% CI 1.86 - 3.85, p < 0.001) they had significantly higher PEDT scores. Additionally, we identified daily sleep of less than six hours, depression, anxiety, diabetes, hyperlipidemia, frequent alcohol consumption (more than twice a week), and erectile dysfunction as risk factors for PE. The predictive model for PE demonstrated commendable efficacy. CONCLUSION: Both shift work and SWSD significantly increase the risk of premature ejaculation, with the risk magnifying in tandem with the duration of shift work. This study reveals the potential impact of shift work and SWSD on PE and provides new theoretical foundations for the risk assessment and prevention of this condition.
Asunto(s)
Eyaculación Prematura , Horario de Trabajo por Turnos , Trastornos del Sueño del Ritmo Circadiano , Humanos , Masculino , Eyaculación Prematura/epidemiología , Adulto , Estudios Transversales , Horario de Trabajo por Turnos/efectos adversos , China/epidemiología , Trastornos del Sueño del Ritmo Circadiano/epidemiología , Persona de Mediana Edad , Factores de Riesgo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Polystyrene nanoplastics (PS-NPs), emerging and increasingly pervasive environmental contaminants, have the potential to cause persistent harm to organisms. Although previous reports have documented local accumulation and adverse effects in a variety of major organs after PS-NPs exposure, the impact of PS-NPs exposure on erectile function remains unexplored. Herein, we established a rat model of oral exposure to 100â¯nm PS-NPs for 28 days. To determine the best dose range of PS-NPs, we designed both low-dose and high-dose PS-NPs groups, which correspond to the minimum and maximum human intake doses, respectively. The findings indicated that PS-NPs could accumulate within the corpus cavernosum and high dose but not low dose of PS-NPs triggered erectile dysfunction. Moreover, the toxicological effects of PS-NPs on erectile function include fibrosis in the corpus cavernous, endothelial dysfunction, reduction in testosterone levels, elevated oxidative stress and apoptosis. Overall, this study revealed that PS-NPs exposure can cause erectile dysfunction via multiple ways, which provided new insights into the toxicity of PS-NPs.
Asunto(s)
Disfunción Eréctil , Estrés Oxidativo , Pene , Poliestirenos , Ratas Sprague-Dawley , Animales , Disfunción Eréctil/inducido químicamente , Masculino , Poliestirenos/toxicidad , Ratas , Estrés Oxidativo/efectos de los fármacos , Pene/efectos de los fármacos , Testosterona/sangre , Nanopartículas/toxicidad , Apoptosis/efectos de los fármacos , Contaminantes Ambientales/toxicidadRESUMEN
Cultivating high-yield wheat under limited water resources is crucial for sustainable agriculture in semiarid regions. Amid water scarcity, plants activate drought response signaling, yet the delicate balance between drought tolerance and development remains unclear. Through genome-wide association studies and transcriptome profiling, we identified a wheat atypical basic helix-loop-helix (bHLH) transcription factor (TF), TabHLH27-A1, as a promising quantitative trait locus candidate for both relative root dry weight and spikelet number per spike in wheat. TabHLH27-A1/B1/D1 knock-out reduced wheat drought tolerance, yield, and water use efficiency (WUE). TabHLH27-A1 exhibited rapid induction with polyethylene glycol (PEG) treatment, gradually declining over days. It activated stress response genes such as TaCBL8-B1 and TaCPI2-A1 while inhibiting root growth genes like TaSH15-B1 and TaWRKY70-B1 under short-term PEG stimulus. The distinct transcriptional regulation of TabHLH27-A1 involved diverse interacting factors such as TaABI3-D1 and TabZIP62-D1. Natural variations of TabHLH27-A1 influence its transcriptional responses to drought stress, with TabHLH27-A1Hap-II associated with stronger drought tolerance, larger root system, more spikelets, and higher WUE in wheat. Significantly, the excellent TabHLH27-A1Hap-II was selected during the breeding process in China, and introgression of TabHLH27-A1Hap-II allele improved drought tolerance and grain yield, especially under water-limited conditions. Our study highlights TabHLH27-A1's role in balancing root growth and drought tolerance, providing a genetic manipulation locus for enhancing WUE in wheat.
Asunto(s)
Sequías , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Raíces de Plantas , Triticum , Agua , Triticum/genética , Triticum/crecimiento & desarrollo , Triticum/fisiología , Triticum/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Agua/metabolismo , Sitios de Carácter Cuantitativo/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Estrés Fisiológico/genética , Estudio de Asociación del Genoma Completo , Resistencia a la SequíaRESUMEN
BACKGROUND: There are several investigations that have revealed that cerebral dopamine (DA) plays a pivotal role in the occurrence of premature ejaculation (PE). Although tyrosine hydroxylase (TH) is an essential enzyme for the synthesis of DA, only few investigations have described the role of TH in regulation mechanisms for ejaculation till now. To investigate whether there is a correlation between TH expression level in the brain and different ejaculation behavior in rats. Then explore whether the TH expression in the brain will change after acute dapoxetine treatment in rats with Rapid ejaculation. METHODS AND RESULTS: Rats (male, S-D rats, 6-8 weeks) were separated into three groups based on their ejaculation frequency: Rapid, Normal, and Sluggish. Expression level of DA in the brain was determined by enzyme-linked immune sorbent assay (ELISA) kit, TH expression level in the brain was determined by immunohistochemistry and Western Blot (WB) techniques. Among the three groups, DA and TH expression level were the highest in the Rapid ejaculation group, while the lowest was the Sluggish ejaculation group. The results also showed that TH level was positively associated with ejaculation frequency (r = 0.8038, P < 0.001) and negatively associated with ejaculation latency (r=-0.6199, P = 0.018). Furthermore, acute dapoxetine therapy in rats with Rapid ejaculation downregulated TH level in the brain. CONCLUSION: Changes in ejaculation behavior were significantly linked with TH level. Upregulated TH in selected brain regions related with ejaculation could cause rapid ejaculation. The effect of dapoxetine in prolonging ejaculation could be related to TH downregulation within the brain.
Asunto(s)
Eyaculación Prematura , Humanos , Masculino , Ratas , Animales , Eyaculación Prematura/tratamiento farmacológico , Tirosina 3-Monooxigenasa , Resultado del Tratamiento , Inhibidores Selectivos de la Recaptación de SerotoninaRESUMEN
Maize is an important crop worldwide, as well as a valuable model with vast genetic diversity. Accurate genome and annotation information for a wide range of inbred lines would provide valuable resources for crop improvement and pan-genome characterization. In this study, we generated a high-quality de novo genome assembly (contig N50 of 15.43 Mb) of the Chinese elite inbred line RP125 using Nanopore long-read sequencing and Hi-C scaffolding, which yield highly contiguous, chromosome-length scaffolds. Global comparison of the RP125 genome with those of B73, W22, and Mo17 revealed a large number of structural variations. To create new germplasm for maize research and crop improvement, we carried out an EMS mutagenesis screen on RP125. In total, we obtained 5818 independent M2 families, with 946 mutants showing heritable phenotypes. Taking advantage of the high-quality RP125 genome, we successfully cloned 10 mutants from the EMS library, including the novel kernel mutant qk1 (quekou: "missing a small part" in Chinese), which exhibited partial loss of endosperm and a starch accumulation defect. QK1 encodes a predicted metal tolerance protein, which is specifically required for Fe transport. Increased accumulation of Fe and reactive oxygen species as well as ferroptosis-like cell death were detected in qk1 endosperm. Our study provides the community with a high-quality genome sequence and a large collection of mutant germplasm.
Asunto(s)
Genoma de Planta/genética , Zea mays/genética , Productos Agrícolas , Endospermo/genética , Endospermo/metabolismo , Endogamia , Mutación , Fenotipo , Fitomejoramiento , Banco de Semillas , Semillas/genética , Semillas/metabolismo , Almidón/metabolismo , Zea mays/metabolismoRESUMEN
Maize height is determined by the number of nodes and the length of internodes. Node number is driven by intercalary meristem formation and internode length by intercalary cell elongation, respectively. However, mechanisms regulating establishment of nodes and internode growth are unclear. We screened EMS-induced maize mutants and identified a dwarf mutant zm66, linked to a single base change in TERMINAL EAR 1 (ZmTE1). Detailed phenotypic analysis revealed that zm66 (zmte1-2) has shorter internodes and increased node numbers, caused by decreased cell elongation and disordered intercalary meristem formation, respectively. Transcriptome analysis showed that auxin signalling genes are also dysregulated in zmte1-2, as are cell elongation and cell cycle-related genes. This argues that ZmTE1 regulates auxin signalling, cell division, and cell elongation. We found that the ZmWEE1 kinase phosphorylates ZmTE1, thus confining it to the nucleus and probably reducing cell division. In contrast, the ZmPP2Ac-2 phosphatase promotes dephosphorylation and cytoplasmic localization of ZmTE1, as well as cell division. Taken together, ZmTE1, a key regulator of plant height, is responsible for maintaining organized formation of internode meristems and rapid cell elongation. ZmWEE1 and ZmPP2Ac-2 might balance ZmTE1 activity, controlling cell division and elongation to maintain normal maize growth.
Asunto(s)
Meristema , Zea mays , Ciclo Celular , Regulación de la Expresión Génica de las Plantas/genética , Ácidos Indolacéticos , Meristema/genética , Zea mays/genéticaRESUMEN
The heavy metal cadmium is proposed to be one of the environmental endocrine disruptors of spermatogenesis. Cadmium-induced inhibition of spermatogenesis is associated with a hormone secretion disorder. Letrozole is an aromatase inhibitor that increases peripheral androgen levels and stimulates spermatogenesis. However, the potential protective effects of letrozole on cadmium-induced reproductive toxicity remain to be elucidated. In this study, male mice were administered CdCl2 (4 mg/kg BW) orally by gavage alone or in combination with letrozole (0.25 mg/kg BW) for 30 days. Cd exposure caused a significant decreases in body weight, sperm count, motility, vitality, and plasma testosterone levels. Histopathological changes revealed extensive vacuolization and decreased spermatozoa in the lumen. However, in the Cd + letrozole group, letrozole treatment compensated for deficits in sperm parameters (count, motility, and vitality) induced by Cd. Letrozole treatment significantly increased serum testosterone levels, which were reduced by Cd. Histopathological studies revealed a systematic array of all germ cells, a preserved basement membrane and relatively less vacuolization. For a mechanistic examination, RNA-seq was used to profile alterations in gene expression in response to letrozole. Compared with that in the Cd-treated group, RNA-Seq analysis showed that 214 genes were differentially expressed in the presence of letrozole. Gene ontology (GO) enrichment analysis and KEGG signaling pathway analysis showed that steroid biosynthetic processes were the processes most affected by letrozole treatment. Furthermore, we found that the expression of the testosterone synthesis-related genes LHCGR (luteinizing hormone/choriogonadotropin receptor) and Hsd3b6 (3 beta- and steroid delta-isomerase 6) was significantly downregulated in Cd-treated testes, but these genes maintained similar expression levels in letrozole-treated testes as those in the control group. However, the transcription levels of inflammatory cytokines, such as IL-1ß and IL-6, and oxidative stress-related genes (Nrf2, Nqo1, and Ho-1) showed no changes. The present study suggests that the potential protective effect of letrozole on Cd-induced reproductive toxicity might be mediated by the upregulation of LHCGR and Hsd3b6, which would beneficially increase testosterone synthesis to achieve optimum protection of sperm quality and spermatogenesis.
Asunto(s)
Cadmio , Letrozol , Espermatogénesis , Testosterona , Animales , Masculino , Ratones , Cadmio/toxicidad , Citoprotección/efectos de los fármacos , Citoprotección/genética , Letrozol/farmacología , Redes y Vías Metabólicas/efectos de los fármacos , Redes y Vías Metabólicas/genética , Ratones Endogámicos ICR , Sustancias Protectoras/farmacología , Receptores de HL/efectos de los fármacos , Receptores de HL/genética , Receptores de HL/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Espermatogénesis/efectos de los fármacos , Espermatogénesis/genética , Espermatozoides/efectos de los fármacos , Espermatozoides/metabolismo , Esteroide Isomerasas/efectos de los fármacos , Esteroide Isomerasas/genética , Esteroide Isomerasas/metabolismo , Testículo/efectos de los fármacos , Testículo/metabolismo , Testosterona/biosíntesisRESUMEN
BACKGROUND: Non-obstructive azoospermia (NOA) is the most severe type of male infertility, affecting 1% of men worldwide. Most of its etiologies remain idiopathic. Although genetic studies have identified dozens of NOA genes, monogenic mutations can also account for a small proportion of idiopathic NOA cases. Hence, this genetic study was conducted to explore the causes of monogenic variants of NOA in a cohort of Chinese patients. METHODS: Following the screening using chromosomal karyotyping, Y chromosome microdeletion analyses, and sex hormone assessments, subsequent whole-exome sequencing analysis was performed in 55 unrelated idiopathic NOA patients with male infertility to explore potential deleterious variants associated with spermatogenesis. We also performed Sanger sequencing to demonstrate the variants. Testicular biopsy or microsurgical testicular sperm extraction was also performed to confirm the diagnosis of NOA and identify spermatozoa. Hematoxylin and eosin staining was performed to assess the histopathology of spermatogenesis. RESULTS: Abnormal testicular pathological phenotypes included Sertoli cell-only syndrome, maturation arrest, and hypospermatogenesis. Using bioinformatics analysis, we detected novel variants in two recessive genes, FANCA (NM_000135, c.3263C > T, c.1729C > G) and SYCE1 (NM_001143763, c.689_690del); one X-linked gene, TEX11 (NM_031276, c.466A > G, c.559_560del); and two dominant genes, DMRT1 (NM_021951, c.425C > T, c.340G > A) and PLK4 (NM_001190799, c.2785A > G), in eight patients, which corresponded to 14.55% (8/55) of the patients. CONCLUSION: This study presented some novel variants of known pathogenic genes for NOA. Further, it expanded the variant spectrum of NOA patients, which might advance clinical genetic counseling in the future.
Asunto(s)
Azoospermia , Infertilidad Masculina , Oligospermia , Azoospermia/diagnóstico , Humanos , Infertilidad Masculina/genética , Infertilidad Masculina/patología , Masculino , Proteínas Serina-Treonina Quinasas , Espermatogénesis/genética , Testículo/patologíaRESUMEN
BACKGROUND: Many studies have reported a possible strong relationship between poor sleep quality, sleep disruption, sleep disorders, and erectile dysfunction (ED). AIM: This study aimed to investigate the relationship between sleep quality and ED. METHODS: Patients diagnosed with ED by the International Index of Erectile Function-5 (IIEF-5) questionnaire and 72 healthy adult men were included. Participants completed the questionnaire, underwent a detailed physical examination, and provided blood samples. All enrolled subjects then wore the Fitbit Charge 2 that monitored sleep throughout the night. OUTCOMES: Primary outcome measures included scores on the IIEF-5, General Anxiety Disorder-7 (GAD-7) scale, Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and sleep monitoring parameters obtained from Fitbit Charge 2. RESULTS: Finally, a total of 107 ED patients and 72 healthy adult men were enrolled in this study. Univariate analysis indicated that the GAD-7 (P < .001), PHQ-9 (P < .001), and PSQI scores (P < .001) significantly differed according to the presence/absence of ED. Further multiple logistic regression analysis showed that the PHQ-9 (odds ratio [OR]: 1.227, 95% confidence interval [CI]: 1.070-1.407; P = .003) and PSQI scores (OR: 1.220, 95%CI: 1.116-1.334; P < .001) were independent risk factors for ED. Analysis of objective sleep monitoring parameters showed that total sleep time (TST) (P = .001), sleep onset latency (SOL) (P = .026), deep sleep (N3) duration (P = .011) and rapid eye movement (REM) sleep duration (P < .001) were significantly differed between the 2 groups, with durations in the ED group significantly lower than those in the non-ED group. In addition, receiver operating characteristic (ROC) curve analysis indicated that the REM sleep duration had the highest area under the curve (AUC: 0.728) of all sleep parameters, with a P value < .001, a sensitivity of 72.2% and a specificity of 73.8%. CLINICAL IMPLICATIONS: Urologists and andrologists should be aware of impacted sleep quality and depression in ED patients. STRENGTHS & LIMITATIONS: The strength of this study is that the relationship between sleep quality and ED was assessed with both a subjective scale and an objective sleep monitoring tool. However, our study only described an association between sleep quality and ED and did not establish a causal relationship. CONCLUSION: Sleep parameters are strongly associated with ED, indicating that poor sleep quality may increase the likelihood of ED. Wu X, Zhang Y, Zhang W, et al. The Association Between Erectile Dysfunction and Sleep Parameters: Data from a Prospective, Controlled Cohort. J Sex Med 2022;19:1387-1396.
Asunto(s)
Disfunción Eréctil , Adulto , Estudios de Cohortes , Humanos , Masculino , Estudios Prospectivos , Factores de Riesgo , SueñoRESUMEN
BACKGROUND: A connection between multiple sclerosis (MS) and erectile dysfunction (ED) has been debatable. AIM: To assess the pooled prevalence of ED among men with MS and whether MS was a risk factor for ED. METHODS: A systematic review of the literature was conducted in PubMed, Scopus, Web of Science, and the Cochrane Library to find relevant English-language studies published up to February 2022 that assessed the prevalence of ED in MS patients. Two authors independently evaluated the full text of the enrolled studies to determine eligibility, and if there was disagreement, the decision was made by a third author after discussion. Assessment tools adapted for prevalence studies were used to evaluate the quality of cross-sectional studies, and the quality of case-control studies was assessed by Newcastle-Ottawa scale. The relative risk (RR) and its 95% confidence interval (CI) were used to assess the strength of association between MS and the risk of ED. The sources of heterogeneity were investigated by subgroup analysis. Sensitivity analysis was conducted to evaluate the stability of the results. OUTCOMES: The pooled prevalence of ED in MS patients as well as 95% CIs were estimated, and the RR and its 95% CI were used to assess the strength of association between MS and the risk of ED. RESULTS: Sixteen studies included collectively gave information about ED in 2,760 MS men, resulting in a pooled prevalence of 49% (95% CI = 42-56%) for ED with a large heterogeneity. Synthesis of results revealed that MS was significantly associated with an increased risk of ED (RR = 3.17, 95% CI = 2.31-4.36, P < .001; heterogeneity: I2 = 0.0%, P = .716). The pooled prevalence estimates of ED were 55, 63, and 57% in the age >40, IIEF diagnostic tool, and mean disease duration >10 years subgroups, respectively. CLINICAL IMPLICATIONS: The present meta-analysis indicates that MS patients had a significantly increased risk of ED, which should raise awareness of the potential association between MS and ED by clinicians. STRENGTHS & LIMITATIONS: This is the first meta-analysis to provide the global prevalence of ED in MS patients and to demonstrate that MS is a risk factor for ED. However, all enrolled studies were observational in design, which may reduce the robustness of this evidence. CONCLUSION: Results of this meta-analysis showed that ED was highly prevalent in adult men with MS and MS was a potential risk factor for ED development. Wu X, Zhang Y, Zhang W, et al. Erectile Dysfunction in Multiple Sclerosis: A Prevalence Meta-Analysis and Systematic Review. J Sex Med 2022;19:1255-1268.
Asunto(s)
Disfunción Eréctil , Esclerosis Múltiple , Adulto , Niño , Estudios Transversales , Disfunción Eréctil/epidemiología , Disfunción Eréctil/etiología , Humanos , Masculino , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/epidemiología , Prevalencia , Factores de RiesgoRESUMEN
BACKGROUND: Erectile dysfunction (ED) may be common in patients with inflammatory bowel disease (IBD), but its prevalence and risk factors still remain debatable. AIM: To evaluate the prevalence of ED in the IBD population and the potential role of risk factors in the development of ED. METHODS: An extensive search in the PubMed, Cochrane Library, and Web of Science was performed to identify relevant English-language articles published up to December 2021 that evaluated the prevalence of ED on IBD patients. The included studies were evaluated by 2 independent reviewers for eligibility. We used an adapted Assessment Tool for Prevalence Studies to evaluate the quality of enrolled studies. Data were analyzed and graphed using the STATA software (version 16.0; Stata Corporation, College Station, TX, USA). The ORs with 95% CIs were pooled using a fixed or random-effects model according to heterogeneity. Subgroup analysis was performed to explore the source of heterogeneity. Sensitivity analysis was conducted to evaluate the stability of the results. OUTCOMES: The pooled prevalence of ED in IBD patients was calculated, and the OR value and 95% CIs were used to assess the strength of the association between IBD-related risk factors and ED. RESULTS: Fourteen studies included 32,858 individuals totally were enrolled for this meta-analysis. The overall pooled prevalence estimate of ED in IBD patients was 27% (95% CI: 20-34%). Operation (OR 1.28; 95% CI: 1.17-1.39; P < .00001; I2 = 0.0%), disease activity (OR 2.06; 95% CI: 1.07-3.05; P < .00001), and depression (crude OR 3.31; 95% CI: 1.08-5.54; P = .004; I2 = 0.0%) significantly increase the risk of ED in people with IBD. The association of depression and ED was further confirmed by calculating the pooled estimates of adjusted OR (1.58; 95% CI: 0.05-3.12; P < .05; I2 = 0.0%). The pooled prevalence estimates of ED were 30, 33, and 17% in the age <40, IIEF diagnostic tool, and IPAA surgery subgroups, respectively. CLINICAL IMPLICATIONS: IBD patients had a significantly increased prevalence of ED, indicating that erectile function in men with IBD should be concerned by clinicians. STRENGTHS & LIMITATIONS: The strength of this study is that this is the first meta-analysis to assess the global prevalence and risk factors of ED in IBD patients. A limitation is that the results after pooling the included articles showed significant heterogeneity. CONCLUSION: The results of our meta-analysis and systematic review provide evidence of the high prevalence and risk factors of ED in IBD patients. Wu X, Zhang Y, Zhang W, et al. The Prevalence and Associated Risk Factors of Erectile Dysfunction in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. J Sex Med 2022;19:950-960.