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Molecular approach to male infertility

[BioNews, London]

Research carried out at the University of Pennsylvania School of Medicine suggests that the packaging of DNA affects the production of sperm and could explain some cases of male infertility.

The production of sperm and eggs (gametes) involves a specialized form of cell division called meiosis, which is tightly regulated by molecular signals in the cell. In a process referred to as 'epigenetics', the expression of genes can be altered without changing the DNA itself. DNA is wrapped around proteins called histones. By chemically changing the histones, DNA is encouraged to bind more or less tightly: this effects the copying of DNA and gene expression.

It is known that sperm and egg formation is influenced strongly by epigenetic mechanisms and the team, led by Professors Shelley Berger and Jerome Govin, set out to identify the importance of histone modification in fertility. The researchers used yeast as an experimental model and developed a way of systematically mutating histone proteins. They screened all the yeast cells to find mutants that were unable to form spores - a process that is analogous to sperm formation in humans.

Their analysis showed that sites on histone proteins H3 and H4 were important. One critical modification site is threonine-11 on histone H3 (H3T11), the phosphorylation of which is required to complete meiosis. They also found a trio of lysines on histone H4, whose acetylation allows efficient compaction of chromosomal DNA into mature spores.

Given the conservation of gamete formation across evolutionary time, it is likely that these epigenetic markers in yeast are also present and serve similar functions in humans. This study may therefore lead to the identification of potential biomarkers for male infertility.

'It is almost certain that some fertility problems relate to epigenetics,' Professor Govin said.

'We are going to find brand new chromatin regulatory mechanisms that will be conserved all the way from yeast to mouse,' Professor Berger predicted.

Reproduced with permission from BioNews, an email and online sources of news, information and comment on assisted reproduction and genetics.