Acquired Sperm DNA Modifications: Causes, Consequences, and Potential Solutions

[摘要] DNA of human spermatozoa can be subject to various kinds of modifications acquired throughout life. Put simply, two basic types of acquired sperm DNA modifications can be distinguished: genetic and epigenetic. Genetic modifications cause alterations of the DNA sequence and mainly result from the formation of breakpoints leading to sperm DNA fragmentation. Epigenetic modifications include a vast spectrum of events that influence the expression of different genes without altering their DNA sequence. Both the genetic and the epigenetic modifications of sperm DNA can negatively influence embryonic development, cause miscarriages, and be the origin of different health problems for the offspring. As to sperm DNA fragmentation, reliable diagnostic methods are currently available. On the other hand, the detection of potentially harmful epigenetic modifications in spermatozoa is a much more complicated issue. Different treatment options can be chosen to solve problems associated with sperm DNA fragmentation. Some are relatively simple and noninvasive, based on oral treatments with antioxidants and other agents, depending on the underlying cause. In other cases, the recourse to different micromanipulation-assisted in vitro fertilisation techniques is necessary to select spermatozoa with minimal DNA damage to be injected into oocytes. The treatment of cases with epigenetic DNA modifications is still under investigation. Preliminary data suggest that some of the techniques used in cases of extensive DNA fragmentation can also be of help in those of epigenetic modifications; however, further progress will depend on the availability of more reliable diagnostic methods with which it will be possible to evaluate the effects of different therapeutic interventions.

[学科分类] 经济地理

[关键词] Diagnosis and treatment;DNA fragmentation;DNA methylation;epigenetic modifications;embryonic;fetal and offspring health;genetic modifications;small RNA species;sperm DNA.