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Low Sperm Count

Men suffering fertility problems because of a low sperm count may have flaws in the fundamental programming of their genes, known as imprinting.

Nearly a quarter of men with low sperm counts showed problems with the on/off switch - or imprint - governing a crucial gene, revealed a new study of men undergoing male fertility treatment. And if the control of one gene is impaired, this means others may also be defective, says Cristina Joana Marques, at the University of Porto in Portugal, and one of the research team.

"We have found a connection between low sperm counts and imprinting effects - the first time someone has done that," says Marques. "We don't know if this could be a cause of the low sperm count, but we know it's an association."

Furthermore, the discovery may mean that men whose low sperm count is related to imprinting problems could also pass these defects on to children they conceive via assisted reproductive technologies like in-vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI).

"The less sperm you have, the more the increased risk of transmitting imprinting defects," Marques was quoted as saying.

"This study adds to our concerns that there are unrecognised problems in male fertility," says Richard Sharpe, an expert in male reproductive development at the Medical Research Council's Human Reproductive Sciences Unit in Edinburgh, UK. "It would suggest that you may indeed pass on general effects to offspring, which might have consequences."

Sperm genes

Everyone inherits two copies of every gene - one from their mother and one from their father. However, only one is needed and imprinting is the mechanism which shuts down one of the copies. The pattern of imprinting is thought to be crucial in the normal development of an embryo.

Imprinting is achieved by the adding or removal of chemical tags that indicate whether a gene is on or off. Adding a methyl group to a cytosine - one of the four chemical "letters" that makes up DNA - in the promoter region of a gene switches it off.

Marques and her colleagues examined the imprinting of two specific genes in 123 men with fertility problems. One of the genes, MEST, showed no imprinting problems. However, a vital gene which should be methylated in the early sperm, was incompletely tagged in a quarter of the men with low sperm counts. This gene, called H19, is responsible for regulating another gene called IGF2, which is a growth factor.

"IGF2 is very important for the development of the placenta, and its expression is dependent on the methylation of [paternal] H19," explains Marques.

The team believes incorrect or incomplete imprinting on H19 could also have a knock-on effect on embryonic development, as well as the placenta. "This could affect implantation of the embryo, or development of the fetus," she says.

Paul Ellis - Men's Health

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