RESUMO
Gonadotropin-regulated testicular RNA helicase (GRTH/DDX25) is a testis specific member of the DEAD-box family of RNA helicases expressed in meiotic and haploid germ cells which plays an essential role in spermatogenesis. There are two species of GRTH the 56 kDa non-phospho and 61 kDa phospho forms. Our early studies revealed a missense mutation (R242H) of GRTH in azoospermic men that when expressed in COS1-cells lack the phospho-form of GRTH. To investigate the role of the phospho-GRTH species in spermatogenesis, we generated a GRTH knock-in (KI) transgenic mice with the R242H mutation. GRTH-KI mice are sterile with reduced testis size, lack sperm with spermatogenic arrest at round spermatid stage and loss of the cytoplasmic phospho-GRTH species. Electron microscopy studies revealed reduction in the size of chromatoid bodies (CB) of round spermatids (RS) and germ cell apoptosis. We observed absence of phospho-GRTH in the CB of RS. Complete loss of chromatin remodeling and related proteins such as TP2, PRM2, TSSK6 and marked reduction of their respective mRNAs and half-lives were observed in GRTH-KI mice. We showed that phospho-GRTH has a role in TP2 translation and revealed its occurrence in a 3' UTR dependent manner. These findings demonstrate the relevance of phospho-GRTH in the structure of the chromatoid body, spermatid development and completion of spermatogenesis and provide an avenue for the development of a male contraceptive.
Assuntos
RNA Helicases DEAD-box/metabolismo , Infertilidade Masculina/genética , Mutação de Sentido Incorreto , Processamento de Proteína Pós-Traducional , Espermátides/metabolismo , Animais , Aspermia/genética , Aspermia/metabolismo , Aspermia/fisiopatologia , Montagem e Desmontagem da Cromatina , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/fisiologia , Regulação da Expressão Gênica , Infertilidade Masculina/metabolismo , Infertilidade Masculina/fisiopatologia , Masculino , Camundongos , Camundongos Knockout , Fosforilação , Protaminas/genética , Proteínas Serina-Treonina Quinases/genética , Espermátides/patologia , Espermátides/fisiologia , EspermatogêneseRESUMO
The associations between three single nucleotide polymorphisms (SNPs; rs3749897, rs16895863 and rs373341) of UBR2 gene and idiopathic aspermia or oligospermia were investigated in this study by a case-control experiment with 149 fertile and 316 infertile men, including 244 patients with idiopathic aspermia and 72 patients with severe oligospermia. The time-of-flight mass spectrometry (Sequenom MassARRAY® system) was used in this study. A significant difference between the oligospermia men (oligospermia group) and the fertile men (control group) was observed in this research (odds ratio [OR]: 2.764; 95% CI: 95% confidence interval [CI]: 1.171-6.525; P = 0.017), which could indicate that the combined AT-TC-CC genotype in the UBR2 gene (rs16895863, rs373341, rs3749897 respectively) is a possible risk of idiopathic oligospermia for men in Sichuan, China.
Assuntos
Aspermia/genética , Predisposição Genética para Doença , Oligospermia/genética , Polimorfismo de Nucleotídeo Único , Ubiquitina-Proteína Ligases/genética , Adulto , Alelos , China , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Adulto JovemRESUMO
A 41-years old male with short stature, abnormal male sex differentiation, aspermia and schizoid character disorder is described. The patient was studied from clinical, endocrinological and genetic perspectives. Cytogenetical analysis revealed a chromosomic mosaicism formed by two normal lines 45X and 46,XY qh-. Molecular studies on AZF region evidenced that it was conserved. The correlation of the symptoms with the cytogenetic finding is discussed.
Assuntos
Aspermia/genética , Cromossomos Humanos X , Cromossomos Humanos Y , Mosaicismo , Esquizofrenia/genética , Adulto , Aspermia/complicações , Humanos , Cariotipagem , Masculino , Esquizofrenia/complicações , Aberrações dos Cromossomos SexuaisRESUMO
It has been speculated that populations of aspermic Fasciola flukes in Korea and Japan have a close phylogenetic relationship. To evaluate this, we analyzed 33 Korean aspermic Fasciola flukes on the basis of nuclear ribosomal internal transcribed spacer 1 (ITS1) and mitochondrial NADH dehydrogenase subunit 1 (nad1) and cytochrome c oxidase 1 (cox1) sequences. Fh, Fg, and Fh/Fg types were detected in the ITS1 region and displayed the fragment patterns of F. hepatica, F. gigantica, and both species, respectively by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Additionally, three concatenated haplotypes of nad1 and cox1(nad1/cox1) were detected, and 2 of these, Kor1/Kor1 (Fsp1/Fsp1) haplotype and Kor2a/Kor2 (Fsp2/Fsp2) haplotype, were shared by Korean and Japanese aspermic flukes. The Fst value (0.019), calculated using the concatenated sequences, indicated that Korean and Japanese aspermic Fasciola populations were genetically undifferentiated. Interestingly, a combination of the Fh/Fg type and Kor1/Kor1 haplotype was found at the highest frequency in Korean aspermic flukes, whereas the Fg type and Fsp2/Fsp2 haplotype combination was found at a conspicuously high frequency in Japanese aspermic flukes. This indicates that a founder effect caused by the introduction of infected hosts may have played a key role in the introduction of aspermic Fasciola flukes from Korea into Japan.
