RESUMEN
Androgen receptor (AR) mediates androgen activities such as the growth of accessory sex organs, and initiation and promotion of spermatogenesis. There are two trinucleotide polymorphisms (CAG and GGN repeats) in the first exon of AR gene that their association with infertility is still controversial. The variants of both polymorphic repeats were investigated by PCR-Sequencing in 220 infertile men (80 azoospermic, 60 oligospermic and 80 asthenospermic) and 80 healthy fertile controls. AR Expression level was quantified by RT-qPCR on 30 patients (20 patients with nonobstructive azoospermia (NOA) and 10 obstructive azoospermia patients as controls). Our results demonstrated that the medians of CAG and GGN repeats length in infertile group were significantly higher than fertile men (p < 0.05). AR expression results showed a significant increase in SCOS group compared to control (p < 0.05). Long stretches of tandem repeats of AR gene may negatively affect the function of the gene and consequently lead to male infertility. In patients with SCOS, AR expression increases because of the lack of germ cells. Therefore, with increasing AR expression, the probability of SCOS occurrence is also increased. It can be concluded that increasing AR expression in testes tissue decreases the probability of sperm presence.
Asunto(s)
Astenozoospermia/genética , Azoospermia/genética , Oligospermia/genética , Receptores Androgénicos/genética , Síndrome de Sólo Células de Sertoli/genética , Adulto , Azoospermia/patología , Estudios de Casos y Controles , Voluntarios Sanos , Humanos , Irán/epidemiología , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Receptores Androgénicos/metabolismo , Síndrome de Sólo Células de Sertoli/epidemiología , Síndrome de Sólo Células de Sertoli/patología , Recuento de Espermatozoides , Testículo/patología , Repeticiones de Trinucleótidos/genéticaRESUMEN
OBJECTIVE: To investigate the expressions of fibroblast growth factor 9 (FGF9) in normal testes and in testes with Sertoli cell-only syndrome (SCOS), explore the biological function of testicular FGF9, and identify the sequence variants of FGF9 gene in patients with SCOS. DESIGN: Retrospective case study. SETTING: University reproductive clinic. PATIENT(S): Forty-one patients with SCOS, seven with normal spermatogenesis, and 100 controls. INTERVENTION(S): Protein expressions of testicular FGF9 and sequence variants of FGF9 gene in normal controls and patients with SCOS were studied. The biological function and regulation of testicular FGF9 were assessed in vitro. MAIN OUTCOME MEASURE(S): Expression profiles of testicular FGF9, effects of FGF9 on germ cell proliferation, and sequence variants of the FGF9 gene. RESULT(S): FGF9 was predominately expressed in the cytoplasm of Leydig cells of normal testis; its expression was significantly decreased in patients with SCOS. Conditioned medium of FGF9-treated Leydig cells stimulated germ cell proliferation. A promoter polymorphism (c.-712CâT) of the FGF9 gene attenuated the promoter activity, which contributes to one of the causes of its low expression. CONCLUSION(S): In addition to the role of sex determination, FGF9 is expressed in postnatal Leydig cells and is involved in cell-to-cell interaction of testicular function. Aberrant expression of testicular FGF9 is associated with SCOS.
Asunto(s)
Factor 9 de Crecimiento de Fibroblastos/genética , Marcadores Genéticos/genética , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Síndrome de Sólo Células de Sertoli/epidemiología , Síndrome de Sólo Células de Sertoli/genética , Procesos de Determinación del Sexo/genética , Estudios de Asociación Genética , Humanos , Incidencia , Masculino , Mutación/genética , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo , Taiwán/epidemiologíaRESUMEN
OBJECTIVE: To assess the association between genetic variants in the ETV5 gene with nonobstructive azoospermia (NOA) associated with Sertoli cell-only (SCO) syndrome. DESIGN: Genetic association study. SETTING: University. PATIENT(S): Australian men (65 SCO, 53 NOA, and 242 fertile men) and American men (86 SCO and 54 fertile men). INTERVENTION(S): Paraffin-embedded human testicular tissue was sectioned and processed for immunofluorescence. Direct DNA sequencing and polymerase chain reaction-based SNP detection were performed to define genetic variants in the ETV5 gene. MAIN OUTCOME MEASURE(S): The localization of ETV5 in the human testis and the presence of ETV5 genetic variants in fertile and infertile men. RESULT(S): ETV5 is localized to the cytoplasm and nucleus of Sertoli and germ cells in adult human testes. We identified six previously reported and six new genetic variants in the ETV5 gene. Of these, the allele frequency of the homozygous +48845 G>T (TT allele) variant was significantly higher in the SCO and NOA Australian men compared with fertile men. CONCLUSION(S): The homozygous +48845 G>T (TT allele) variant confers a higher risk for male infertility associated with NOA and SCO in Australian men.
Asunto(s)
Azoospermia/genética , Proteínas de Unión al ADN/genética , Fertilidad/genética , Variación Genética/genética , Síndrome de Sólo Células de Sertoli/genética , Factores de Transcripción/genética , Adulto , Empalme Alternativo/genética , Australia/epidemiología , Azoospermia/epidemiología , Azoospermia/patología , Secuencia de Bases , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Datos de Secuencia Molecular , Precursores del ARN/genética , Factores de Riesgo , Síndrome de Sólo Células de Sertoli/epidemiología , Síndrome de Sólo Células de Sertoli/patología , Espermatogonias/patología , Espermatogonias/fisiología , Testículo/patología , Testículo/fisiologíaRESUMEN
Exposure to ubiquitous, environmental chemicals (ECs) has been hypothesized as a cause for declining male reproductive health. Understanding the long-term effects of EC exposure on reproductive health in humans requires animal models and exposure to 'real life', environmentally relevant, mixtures during development, a life stage of particular sensitivity to ECs. The aim of this study was to evaluate the effects of in utero and post-natal exposure to environmentally relevant levels of ECs, via sewage sludge application to pasture, on the adult male sheep testis. Hormones, liver concentrations of candidate ECs and Sertoli and germ cell numbers in testes of adult rams that were exposed to ECs in sewage sludge in utero, and until weaning via maternal exposure, and post-weaning via grazing pastures fertilized with sewage sludge, were quantified. Evaluated as a single group, exposure to sludge ECs was without significant effect on most parameters. However, a more detailed study revealed that 5 of 12 sludge-exposed rams exhibited major spermatogenic abnormalities. These consisted of major reductions in germ cell numbers per testis or per Sertoli cell and more Sertoli cell-only tubules, when compared with controls, which did not show any such changes. The sludge-related spermatogenic changes in the five affected animals were significantly different from controls (p < 0.001); Sertoli cell number was unaffected. Hormone profiles and liver candidate EC concentrations were not measurably affected by exposure. We conclude that developmental exposure of male sheep to real-world mixtures of ECs can result in major reduction in germ cell numbers, indicative of impaired sperm production, in a proportion of exposed males. The individual-specific effects are presumed to reflect EC effects on a heterogeneous population in which some individuals may be more susceptible to adverse EC effects. Such effects of EC exposure in humans could have adverse consequences for sperm counts and fertility in some exposed males.