Defective sperm
The insidious epigenome is guilty
Sergey Syrov, XX2 century
One in eight couples faces the problem of conceiving a child, and almost a quarter of these cases are "unexplained" male infertility. Over the past decade, studies have linked such infertility to defective spermatozoa, which during spermatogenesis cannot get rid of proteins known as histones. But the mechanisms behind this process, both in the normal and pathological development of the male germ cell, remained unclear.
An article written by specialists of the University of Pennsylvania School of Medicine (University of Pennsylvania School of Medicine) published in the journal Developmental Cell (Luense et al., Gcn5-Mediated Histone Acetylation Governs Nucleosome Dynamics in Spermiogenesis). It reports on the results of a genetic study revealing both the localization of the remaining "extra" histones and the key protein responsible for their removal.
Epigenetic factors play an important role in the formation of sperm and eggs. It is very important to be able to track their influence – both in order to find ways to treat male infertility, and to control hereditary diseases that are not transmitted through DNA.
Healthy spermatozoa lose 90 to 95 percent of histones, the main chromatin proteins that serve to "package" DNA and turn genes on and off. Histones are replaced by smaller protamine proteins, which allows the DNA to be repackaged correctly into tiny spermatozoa. Considering the role of preserved histones in infertility and disorders of embryonic development, it is important to identify the genomic loci associated with them – potential targets of therapy.
Past studies on the location of histones have yielded contradictory results.
"There were disagreements in trying to understand these contradictory data," says the first author of the study, Professor Lacey J. Luense. – We found that both of the previously described models are correct. We find histones on genes that seem important for embryo development, but we also find them on repetitive elements, places that need to be turned off and prevent the expression of these regions in the embryo."
What will knowledge about epigenetic inheritance bring to mankind? Perhaps it will reduce the pressure on women a little – after all, they are often perceived as the main carriers of reproductive health.
"Currently, the burden of IVF and other assisted reproductive technologies falls on women. Even if the problem is on the man's side, women should still undergo hormone therapy and procedures," notes another author of the study, Professor Shelley L. Berger. – And now imagine that you can apply epigenetic therapy to change the level of histones and protamines in men before embryogenesis. This is one of the issues that we want to explore, and the results we have achieved allow us to move in this direction."
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