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Influence of sperm DNA fragmentation on early embryo development

Grant number: 21/03753-6
Support type:Scholarships in Brazil - Master
Effective date (Start): October 01, 2021
Effective date (End): July 31, 2023
Field of knowledge:Health Sciences - Medicine
Principal researcher:Ricardo Pimenta Bertolla
Grantee:Mika Alexia Miyazaki
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Seminal parameters such as concentration, motility and morphology are widely used to study male infertility. However, recent years it has been observed that genetic and epigenetic abnormalities have negatively influenced reproductive outcomes and contributed to the diagnosis of idiopathic male infertility. Among them, we highlight the sperm DNA fragmentation, a common phenomenon but when it is increased leads to a lower male reproductive capacity. Among the main causes of DNA fragmentation we can mention oxidative stress, irregularities in protamination, abortive apoptosis and elevated testicular and epididymal temperatures. Studies have shown that the paternal genome plays a fundamental role in events at the beginning of embryo development, such as epigenetic regulation, cleavage, implantation and mainly in the formation of the placenta and extra-embryonic tissues, since they undergo genomic imprinting, an event which the expression of an allele of the gene depends on its parenteral origin. We highlight PEG1, PEG3, PEG9, PEG10 and PEG11, genes that undergo paternal imprinting and are fundamental to placenta development. Their absence can result in placental abnormalities and fetal growth restriction. This study aims to evaluate the effect of the degree of fragmentation on the expression of these genes in sperm. For this, quantitative PCR, Comet Alkaline Assay and TUNEL Test will be performed, using the animal model of rats exposed to high temperatures and induced to varicocele. In addition, to verify the results in in vitro reproduction, the fertilization, cleavage and blastocyst formation rates will be calculated.

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