Male subfertility is now an open subject and the more we know about it the better it can be treated.
The purity of DNA in sperm is essential for fertilisation, resulting in high quality embryo development, implantation, pregnancy and healthy babies. After fertilization occurs, a male and female pronucleus containing genetic material appears. The fusion of these pronuclei is followed by DNA replication and zygotic divisions. Zygotic transcription begins early in the developmental stage and is essential for normal embryonic development. DNA damage can result in errors in DNA replication which can lead to abnormalities in chromosomes and genetic variations. Hence, any DNA abnormalities can significantly affect the quality of the sperm, its motility, the fertilization process, embryo development and lead to implantation failures as well, thereby having a substantial impact on assisted reproduction techniques (ART).
DNA is a double-stranded spiral structure. SDF (sperm DNA fragmentation) can occur due to SSBs (single strand breaks) or DSBs (double strand breaks). Alteration or break at one of the strands is a SSB. DSB is where both strands are damaged or broken. From recent studies, it shows that the two types of sperm DNA breaks have different effects in clinical reproduction. Single strand breaks are more common and present as multiple breakpoints. They can be restored with a DNA repair mechanism. These are related to oxidative stress and may impact clinical pregnancy or increase the conception time. Double strand breaks are rare and usually relate to lack of innate DNA repair mechanisms. They have been found to raise the miscarriage risk, lower embryo quality and cause a higher risk of implantation failure.
There are various causes of DNA damage – apart from defective spermatogenesis, some of them are:
- Abortive apoptosis: Apoptosis is a type of cell death, which helps get rid of abnormal cells. Germ cell apoptosis accompanies spermatogenesis and is an important factor in retaining the best cells. Abortive apoptosis has been described as those damaged cells which escape the apoptosis process.
- Abnormalities in chromatin remodelling: Chromatin fibres form chromosomes and chromatin enables many cell processes to occur, such as DNA replication, repair, transcription, cell division and recombination. Abnormalities in the remodelling could result in DNA damage.
- Oxidative stress results in defective cells which cause DNA damage and lead to DNA fragmentation and cell death.
- Oxidative stress is formed when the ROS (reactive oxygen species) exceeds the antioxidant defences.
Lifestyle factors such as smoking, obesity, excessive exercise, exposure to chemicals and radiation and even age can impact the quality of DNA.
Tests for DNA damage:
Realisation of the impact that damaged DNA can have on sperm and ART has magnified the importance of testing the DNA quality. Some of the major tests being used for this purpose are the SCSA (sperm chromatin structure assay), TUNEL, Comet assay and SCD (sperm chromatin dispersion). Each uses a different method to analyse the sperm DNA quality. The identification of various levels of SDF and DNA damage can help the Infertility specialist to choose the most suitable sperm selection technique and appropriate ART treatment to raise the chances of a successful pregnancy.
Conclusion:
Breaks in single or double strand DNA can lead to errors in DNA Fragmentation test replication resulting in chromosomal abnormalities and genetic mutations which decrease fertility and affect fertility processes. DSBs can be repaired molecularly only in the early stages of spermatogenesis. Hence, the effect of DSBs on ART procedures is higher. More research is needed and is still ongoing to define the effect of SSBs and DSBs in sperm on reproductive processes.
Meanwhile, we at Andrology Center are proud to state that we are the only authorised laboratory in India to carry out the SCSA (sperm chromatin structure assay) test. Besides the regular semen analysis, the SDF test carried out by us guarantees accurate results, with the high technology methods and state-of-the-art equipment used. Such results will assist the specialist and patients in choosing procedures to improve the success rate of ART and lower the risk of adverse outcomes.
