Topology of chromosome centromeres in human sperm nuclei with high levels of DNA damage.

Ewa Wiland,Maciej Kurpisz,Monika Fraczek,Marta Olszewska

doi:10.1038/srep31614

Ewa Wiland, Maciej Kurpisz + Show 2 more

Open Access

https://doi.org/10.1038/srep31614

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Abstract

Several studies have shown that the ‘poor’ sperm DNA quality appears to be an important factor affecting male reproductive ability. In the case of sperm cells from males with the correct somatic karyotype but with deficient spermatogenesis, resulting in a high degree of sperm DNA fragmentation, we observed changes in the preferential topology of the chromosome 7, 9, 15, 18, X and Y centromeres. The changes occurred in radial localization and may have been directly linked to the sperm chromatin damage. This conclusion is mainly based on a comparison of FISH signals that were observed simultaneously in the TUNEL-positive and TUNEL-negative sperm cells. The analyzed cells originated from the same ejaculated sample and FISH was performed on the same slides, after in situ TUNEL reaction. Based on the observed changes and previous data, it appears that the sperm nucleus architecture can be disrupted by a variety of factors and has a negative influence on spermatogenesis at the same time. Often, these factors coexist (e.g. chromosomal translocations, aneuploidies, a higher DNA fragmentation, abnormal seminology), but no direct correlations between the factors were observed.

Highlights

A meta-analysis has shown that a high-degree sperm of DNA fragmentation has a detrimental effect on in vitro fertilization (IVF)/ICSI outcome: high sperm DNA damage was associated with low pregnancy rates in IVF but not in ICSI cycles but was associated with high miscarriage rates in ref
The aim of this study was to determine whether the deficient spermatogenesis that is manifested by ‘poor’ sperm DNA/chromatin quality may interfere with chromosome topology changes in sperm cells
Numerous cut offs associated with the level of DNA damage have been reported in the literature

Summary

Introduction

It has been suggested that the described intranuclear architecture is of considerable importance for the correct decondensation of chromatin in the male pronucleus[16,17]. It appears that the chronology of the zygotic genome activation is more dependent on the changes in the chromatin structure than on transcription factor activation[18,19]. Few studies have described the changes in the sperm cell chromosomes topology in men with reproductive failures and the correct somatic karyotype[21,22,23,24,25,26]. Sperm DNA integrity can be disrupted by at least three mechanisms: defective chromatin packaging, apoptosis and oxidative stress[33,36]

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