RESUMO
The expression of interleukin-11 (IL-11) and its products STAT3 and phospho-STAT3 (p-STAT3) in patients with chronic superficial gastritis (CSG), chronic atrophic gastritis (CAG), and gastric cancer (GC) may provide insight into the diagnostic role of the IL-11/STAT3 signaling pathway in GC. Gastric mucosa specimens and serum samples were collected from 90 patients with CSG, CAG, and GC (30/group). The expression of IL-11, STAT3, and p-STAT3 was detected via immunohistochemistry and western blot. Additionally, serum levels of IL-11 were measured by enzyme-linked immunosorbent assay. For IL-11, 60% stained positive in CAG and 83.3% stained positive in GC, which were both higher than the value observed for CSG (33.3%). Moreover, the percent positive for IL-11 in GC was higher than that in CAG (P < 0.05). The percent positive for STAT3 in CAG (80%) and GC (83.3%) was higher than that in CSG (53.3%) (P < 0.05). Compared with CSG (36.7%), the percent positive for p-STAT3 in CAG (63.3%) and GC (86.7%) was also significantly higher. STAT3 expression was similar in GC and CAG, which was significantly higher than that in CSG. Expectedly, p-STAT3 expression gradually increased from CSG to CAG to GC. Furthermore, p-STAT3 levels were higher in GC tissues than in CAG (P < 0.01). Intriguingly, serum IL-11 levels gradually increased from CSG to CAG to GC, which coincided with disease severity. Together, these results suggest that the IL-11/STAT3 signaling pathway plays a critical role in human CAG, and may provide new targets to prevent and treat GC.
Assuntos
Gastrite Atrófica/genética , Interleucina-11/biossíntese , Fator de Transcrição STAT3/biossíntese , Neoplasias Gástricas/genética , Idoso , Feminino , Mucosa Gástrica/patologia , Gastrite Atrófica/patologia , Humanos , Interleucina-11/genética , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Fator de Transcrição STAT3/genética , Transdução de Sinais , Neoplasias Gástricas/patologiaRESUMO
We investigated azoospermia region microdeletions in male infertility patients with Klinefelter syndrome (KFS), as well as the association between azoospermia symptoms in patients with KFS and Y chromosome microdeletion polymorphisms. A total of 111 cases with male infertility confirmed to have KFS (47, XXY) and 94 fertile men were included in this study. Peripheral blood was drawn and DNA was extracted from these samples. Multiplex polymerase chain reaction was performed to screen the partial deletions of 25 sequence-tagged sites on the Y chromosome. In 111 cases with KFS, 1 case contained the AZFb+d+c deletion. The Gr/Gr deletion was identified in 12 KFS cases and 5 control cases. In addition, the b2/b3 deletion was identified in 13 KFS cases and 6 control cases. There were no significant differences in phenotype and genotype of the 2 partial AZFc deletions between patients and controls (P > 0.05). Our results suggest that patients with KFS may also have Y chromosome microdeletions to varying degrees and that the gr/gr deletion and b2/b3 deletion may not play a role in the susceptible genetic background of azoospermia in patients with KFS in the Sichuan population.
Assuntos
Síndrome de Klinefelter/genética , Proteínas de Plasma Seminal/genética , Azoospermia/genética , Deleção Cromossômica , Cromossomos Humanos Y/genética , Deleção de Genes , Loci Gênicos/genética , Humanos , Infertilidade Masculina/genética , Masculino , Fenótipo , Sitios de Sequências Rotuladas , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genéticaRESUMO
Previous studies have shown that genetic polymorphisms in exon7 of the NSUN7 gene can be used as an infertility marker in Iranian men with asthenospermia. However, there have been no equivalent studies in China. In the present study, we investigated the possible association between the genetic polymorphisms in exon7 of NSUN7 and asthenospermia in a Chinese Han population. We recruited 240 asthenospermic men as a patient group and 256 normospermic men as a control group, and analyzed the semen parameters on the basis of World Health Organization (WHO) guidelines. The genetic polymorphisms in exon7 of NSUN7 were detected by DNA sequence analysis. The results were analyzed statistically and a P value < 0.05 was considered significant. There were two genetic polymorphisms, c.906C>T and c.922T>G, in exon7 of NSUN7. We found relatively similar genotypes and allele frequencies between the two groups (P = 0.928, P = 0.928, respectively). The combined genotypes of the two polymorphisms did not identify a haplotype associated with asthenospermia (P = 0.824, P = 0.824, respectively). Our findings revealed that genetic polymorphisms in exon7 of the NSUN7 gene are not associated with asthenospermia in Chinese Han men.
Assuntos
Povo Asiático/genética , Astenozoospermia/genética , Éxons , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Estudos de Casos e Controles , China , Frequência do Gene , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA , Adulto JovemRESUMO
We examined the association between the methionine synthase reductase (MTRR A66G), methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), and methionine synthase (MS A2756G) genotypes and non-obstructive male infertility in a Chinese population. This case-control study included 162 infertile Chinese patients with azoospermia (N = 100) or oligoasthenozoospermia (N = 62) and 120 fertile men as controls. The polymorphisms MTRR A66G, MTHFR C677T, A1298C, and MS A2756G were identified by direct DNA sequencing and the results were statistically analyzed. We found no association between the incidence of any of these variants in azoospermia patients and control populations. The frequency of the MTRR66 polymorphic genotypes (AG, AG+GG) was significantly higher in the oligoasthenozoospermia group compared to the controls (P = 0.013, 0.012). Our findings revealed an association between the single-nucleotide polymorphism A66G in the MTRR gene and male infertility, particularly in oligoasthenozoospermia males, suggesting that this polymorphism is a genetic risk factor for male infertility in Chinese men.
Assuntos
Ferredoxina-NADP Redutase/genética , Predisposição Genética para Doença/genética , Infertilidade Masculina/genética , Polimorfismo de Nucleotídeo Único , Alelos , Povo Asiático/genética , Azoospermia/etnologia , Azoospermia/genética , Sequência de Bases , Estudos de Casos e Controles , China , Análise Mutacional de DNA , Frequência do Gene , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Infertilidade Masculina/etnologia , MasculinoRESUMO
We investigated the molecular genetic mechanism of sex reversal by exploring the relationship between mutations in the sex-determining genes SRY, SOX9, and DAX1 with genetic sex reversal disease. Mutations in the three key genes were detected by polymerase chain reaction (PCR) and sequencing after karyotype analysis. The mutations detected were then aligned with a random sample of 100 normal sequences and the NCBI sequence database in order to confirm any new mutations. Furthermore, the copy number of SOX9 was measured by fluorescence quantitative PCR. Seven of the 10 male sex reversal patients (46, XX) contained an excess copy of the SRY gene, while one of the eight female sex reversal patients (46, XY) was lacking the SRY gene. Additionally, a new mutation (T-A, Asp24Lys) was detected in one female sex reversal patient (46, XY). No other mutation was detected in the analysis of SOX9 and DAX1, with the exception of an insertion mutation (c.35377791insG) found in the testicular-specific enhancer (TESCO) sequences in an SRY-positive female sex reversal patient (46, XY). Eight of the 18 sex reversal cases (44.4%) showed obvious connections with SRY gene translocations, mutations, or deletions, which was significantly higher than that reported previously (33.3%), indicating a need to further expand the range of sample collection. Overall, these results indicated that the main mechanism of sex reversal are not associated with mutations in the coding regions of SOX9 and DAX1 or copy number variations of SOX9, which is consistent with results of previous studies.
Assuntos
Transtornos Testiculares 46, XX do Desenvolvimento Sexual/genética , Receptor Nuclear Órfão DAX-1/genética , Transtornos do Desenvolvimento Sexual/genética , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOXB1/genética , Transtornos Testiculares 46, XX do Desenvolvimento Sexual/patologia , Adulto , China , Variações do Número de Cópias de DNA/genética , Transtornos do Desenvolvimento Sexual/patologia , Feminino , Humanos , Masculino , Mutação , Processos de Determinação SexualRESUMO
Chromosome abnormalities, Y-chromosome microdeletions, and androgen receptor gene CAG and GGN repeat polymorphisms in infertile Chinese men featuring severe oligospermia and azoospermia were analyzed. Ninety-six fertile men and 189 non-obstructive infertile men, including 125 patients with azoospermia and 64 with severe oligozoospermia, were studied. Seventeen infertile men (9.0%) carried a chromosome abnormality. Twenty (10.6%) carried a Y-chromosome microdeletion. In the remainder of the patients and controls, GGN and CAG repeats were sequenced. Short GGN repeats (n < 23) appeared to be associated with defective spermatogenesis, with the number of GGN repeats strongly correlated with sperm counts. No significant difference in CAG repeats was found between patients and controls, nor were CAG repeats correlated with sperm counts. However, for CAG repeats ranging between 24 and 25, there was a >2.5-fold risk (OR = 2.539, 95%CI = 1.206-5.344, P < 0.05) of severe oligospermia and azoospermia. Our results confirmed the significant role of chromosome abnormalities, Y-chromosome microdeletions, and GGN repeats in Chinese male infertility.
Assuntos
Cariótipo Anormal , Azoospermia/genética , Deleção Cromossômica , Variações do Número de Cópias de DNA , Oligospermia/genética , Receptores Androgênicos/genética , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual , Adulto , Estudos de Casos e Controles , China , Cromossomos Humanos Y , Humanos , Infertilidade Masculina , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Contagem de Espermatozoides , Espermatogênese/genéticaRESUMO
The non-recombining portion of the Y-chromosome contains numerous polymorphisms; therefore, it is now the most informative haplotyping system with wide-ranging applications. Idiopathic azoospermia and oligospermia are among the most important causes of male infertility. Different haplogroups may have different genetic backgrounds, which may be either susceptible or unsusceptible to idiopathic azoospermia or oligospermia. This study investigated the possible association between Y-chromosome haplogroup distribution and susceptibility to spermatogenic impairment. Peripheral blood was collected from 193 men with normozoospermia, 193 men with idiopathic azoospermia and 105 men with idiopathic oligospermia. All of the subjects underwent karyotyping, azoospermia factor (AZF) deletion analysis by 15 AZF-specific sequence-tagged sites and Y-chromosome haplotype analysis by 17 binary markers. Excluding men with AZF deletions and abnormal karyotypes, the remainder of these 3 groups was named Group i, Group ii, and Group iii, respectively. The comparisons of 17 Y-haplogroup distributions between Group i and Group ii, Group iii or Group ii + iii were performed with the SPSS V.18.0 software. Significantly different Y-haplogroup distributions were observed between Group i and Group ii in N1* (P = 0.002), between Group i and Group iii in F*, K*, P*, and O3* (P = 0.002, 0.001, 0.004, and 0.007, respectively), and between Group i and Group ii + iii in K*, N1* and O3* (P = 0.008, 0.012, and 0.009, respectively). These results suggest that Y-chromosome haplogroups play a role in spermatogenic impairment.
Assuntos
Povo Asiático/genética , Azoospermia/genética , Cromossomos Humanos Y , Infertilidade Masculina/genética , Espermatogênese/genética , China , Deleção Cromossômica , Predisposição Genética para Doença , Haplótipos , Humanos , Cariotipagem/métodos , Masculino , Oligospermia/genéticaRESUMO
The purpose of this study was to detect chromosomal aberrations and azoospermia factor (AZF) microdeletions in male patients with reproductive problems and to summarize related clinical features to provide reliable information for evaluating prenatal and preimplantation diagnoses. A large cohort of 5083 men with various phenotypes of male infertility was analyzed via G-banding karyotyping, and Origin 8.0 was used to analyze the prevalence of abnormalities. Additionally, patients with azoospermia, oligozoospermia, and oligoasthenozoospermia were analyzed using multiplex polymerase chain reaction to detect microdeletion in the AZF. We identified 387 patients with abnormal karyotypes, and the ratio was 7.61%. Among them were 175 patients with Klinefelter's syndrome, which was the most common numerical chromosomal abnormality and accounted for 45.22% of all chromosomal aberrations. The frequencies of increased satellites, balanced translocations, and Robertsonian translocations were 6.47, 7.00, and 3.62%, respectively. Multiplex polymerase chain reaction performed in 810 cases with azoospermia, oligozoospermia, and oligoasthenozoospermia found a ratio of AZF microdeletions of 4.94%. The finding suggests that chromosomal abnormalities and AZF deletion are main factors that result in male infertility. Detecting these common genetic variations is necessary in infertile men seeking assisted reproductive technology.
Assuntos
Azoospermia/genética , Infertilidade Masculina/genética , Síndrome de Klinefelter/genética , Oligospermia/genética , Aberrações dos Cromossomos Sexuais , China/epidemiologia , Cromossomos Humanos Y/genética , Proteínas de Ligação a DNA/genética , Humanos , Infertilidade Masculina/epidemiologia , Cariotipagem , Masculino , Reação em Cadeia da Polimerase , Diagnóstico Pré-Natal , Técnicas de Reprodução Assistida , Deleção de Sequência/genéticaRESUMO
Primed in situ labeling (PRINS) technique is an alternative to in situ hybridization for rapid chromosome screening. We employed triple-color PRINS technique to detect chromosomal abnormalities in Klinefelter syndrome patients diagnosed by G-banding karyotype analysis. Among 1034 infertile male patients, 134 were found to be cytogenetically abnormal, including 70 with chromosomal number abnormalities and 64 with chromosomal structure abnormalities. Among these cytogenetically abnormal patients, 56 were diagnosed as having Klinefelter syndrome. PRINS technique was used on cultured lymphocyte metaphase cells of the Klinefelter syndrome patients; the same result was obtained with G-banding karyotype analysis. PRINS proved to be a rapid and reliable method to detect numerical chromosome abnormalities in peripheral blood lymphocytes in metaphase.
Assuntos
Bandeamento Cromossômico , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Marcação in Situ com Primers/métodos , Adulto , Aberrações Cromossômicas , Humanos , MasculinoRESUMO
In order to analyze male sterility caused by deletion of SRY and DAZ, we examined the accuracy and cost-effectiveness of a modified primed in situ labeling (PRINS) technique for detection of single-copy genes. Peripheral blood samples were collected from 50 healthy men; medium-term cultured lymphocytes from these samples were suspended in fixative solution and then spread on clean slides. We used four primers homologous to unique regions of the SRY and DAZ regions of the human Y-chromosome and incorporated reagents to increase polymerase specificity and to enhance the hybridization signal. PRINS of SRY and DAZ gave bands at Yp11.3 and Yq11.2, respectively, in all 50 metaphase spreads. The PRINS SRY signals were as distinct as those obtained using traditional fluorescence in situ hybridization (FISH). This new method is ideal for rapid localization of single-copy genes or small DNA segments, making PRINS a cost-effective alternative to FISH. Further enhancement of PRINS to increase its speed of implementation may lead to its wide use in the field of medical genetics.