RESUMO
Alterations affecting the mitochondrial genome and chromatin integrity of spermatozoa impair male reproductive potential. This study aimed to evaluate the impact of mitochondrial DNA (mtDNA) copy number alterations on sperm motility and on the molecular mechanism regulating the number of mtDNA copies, through analysis of mitochondrial transcription factor A (TFAM) gene expression. It also investigated any correlation between mtDNA copy number and sperm DNA fragmentation (SDF). Sixty-three asthenozoospermic semen samples (Group A) and 63 normokinetic semen samples (Group N) were analysed according to WHO (WHO laboratory manual for the examination and processing of human semen, World Health Organization, Geneva, 2010). Sperm mtDNA copy number and TFAM gene expression were quantified by real time quantitative polymerase chain reaction. SDF was evaluated using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay. The mtDNA copy number was higher in asthenozoospermic semen samples and was negatively correlated with sperm concentration, total sperm number and total motile spermatozoa. The caseload showed a global negative correlation of TFAM gene expression with total motile sperm and a positive correlation with abnormal forms, SDF and mtDNA copy number, but this was not confirmed within each subgroup. SDF was significantly increased in asthenozoospermic samples and correlated with abnormal forms. No correlation was found between SDF and mtDNA copy number. Our results suggest a potential role of mtDNA content as an indicator of semen quality and support the hypothesis that dysregulation of TFAM expression is accompanied by a qualitative impairment of spermatogenesis. Since mtDNA copy number alterations and impaired chromatin integrity could affect reproductive success, these aspects should be evaluated in relation to assisted reproductive techniques.
Assuntos
DNA Mitocondrial/genética , Proteínas de Ligação a DNA/genética , Proteínas Mitocondriais/genética , Motilidade dos Espermatozoides/genética , Fatores de Transcrição/genética , Adulto , Astenozoospermia/genética , Variações do Número de Cópias de DNA , Fragmentação do DNA , Proteínas de Ligação a DNA/metabolismo , Expressão Gênica/genética , Humanos , Masculino , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Sêmen/metabolismo , Análise do Sêmen/métodos , Motilidade dos Espermatozoides/fisiologia , Espermatogênese , Espermatozoides/metabolismo , Fatores de Transcrição/metabolismoRESUMO
We describe a dispersion-enabled, ultra-low power realization of super-resolution in an integrated Mach-Zehnder interferometer. Our scheme is based on a Vernier-like effect in the coincident detection of frequency correlated, non-degenerate photon pairs at the sensor output in the presence of group index dispersion. We design and simulate a realistic integrated refractive index sensor in a silicon nitride on silica platform and characterize its performance in the proposed scheme. We present numerical results showing a sensitivity improvement upward of 40 times over a traditional sensing scheme. The device we design is well within the reach of modern semiconductor fabrication technology. We believe this is the first metrology scheme that uses waveguide group index dispersion as a resource to attain super-resolution.
