RESUMO
This review provides up-to-date information on the molecular basis of the pathogenesis of male infertility at the cellular and subcellular levels. The emphasis is on the importance of new next-generation sequencing technologies as a high-performance tool for studying the genome and epigenomic mechanisms, transcriptome, proteome and metabolome of ejaculate, and organs of the reproductive system. This methodology made it possible to identify differentially expressed metabolic and signaling pathways in fertile and infertile men that combine the genotype and phenotype of a particular individual into a single whole. The current ideas about the relationship between oxidative stress and imbalance of redox systems with DNA damage in spermatozoa as the leading mechanism for the development of idiopathic infertility are summarized. The role of miRNAs, methyloma aberrations, deficiency of phospholipase C zeta in spermatozoa in the pathology of fertility is given. Deciphering the molecular profile and molecular phenotypes of infertility as a result of the interaction of genetic and environmental factors is a necessary condition for screening the most informative biomarkers, assessing their stratification potential, and validating new molecules as potential targets for targeted therapy.
Assuntos
Infertilidade Masculina , MicroRNAs , Fertilidade , Humanos , Infertilidade Masculina/etiologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Estresse Oxidativo/genética , Espermatozoides/metabolismoRESUMO
The distribution of polychlorobiphenyls (environmental pollutants) in the reproductive organs and fatty tissues of rats was analyzed and selective accumulation of the toxicants in the epididymis, but not in the ovaries, was demonstrated. Reduction of the fertilizing activity of the ejaculate after chronic exposure to polychlorobiphenyls was detected. Mechanisms of spermatogenic dysfunction under conditions of high technogenic load are discussed.