A protein could be the cause of male infertility

14 May 2014

Fertility problems are not only limited to women. In fact, the NHS estimates that over 2.5 million men experience this problem in their lifetime. New research from Cold Spring Harbor Laboratory (CSHL) suggests the problem could stem from a key event that happens during sperm development.

Sperm is seen as a delivery system, to get male genetic information from his body into the woman’s egg. The cell is little more than a package of DNA powered by molecular motors. It is necessarily tiny so it can move quickly to its end destination. This means that the genetic data must be packed tightly, which can present significant challenges in conceiving a child.

In every cell in the body, DNA is wrapped around protein spools, called histones. Once wrapped, the genetic information can be unwound so it can be accessed. Compared to other cells in the body, the DNA sperm contained in sperm is much more condensed. Histones are replaced with even smaller proteins called protamines This process repackaging process - chromatin remodeling - is essential for male fertility.

The new study, published in the journal Nature Communications, identified a protein, called Chd5, as a key regulator in chromatin remodeling during sperm development.

Professor Alea Mills and her research team removed the gene from male mice and discovered that the animals went on to have significant fertility defects, including low sperm counts and decreased mobility. The defunct cells were then unable to fertilise eggs when in vitro fertilisation (IVF) was performed.

The lead author commented: “We know this ability has something to do with chromatin remodeling -- that when defective, causes normal cells to transform into tumours. But the most dramatic chromatin reorganisation occurs when specialised cells carrying our genetic blueprint develop into sperm cells. It makes sense that Chd5 would be functioning there, too."

Her team discovered that when the protein was missing chromatin remodeling becomes disrupted. Histones are not correctly replaced with protamines to repackage the DNA, which causes the genome to be uneven and less condensed.

This problem can have damaging effects to the DNA contained in sperm. If Chd5 is absent, the double helix becomes impaired and breaks at several points throughout the genome.

“So in addition to infertility, loss of Chd5 may put future generations – the rare embryos that do get fertilised with defective sperm – at risk for disease," says Professor Mills. "Chd5 may protect a person from medical conditions related to DNA damage and spontaneous mutations, like cancer and autism."

The research team analysed levels of the protein using data from biopsies taken from the testes of men experiencing fertility issues. They discovered that men with the most significant defects had the lowest levels of Chd5.

"While it is only a correlation at this point, we are eager to understand fully how Chd5 affects sperm development in humans," Professor Mills concluded.

The research team will continue to study the role of Chd5 in human fertility.

Posted by Edward Bartel

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