Genetic gold standard could help diagnose and treat male infertility.
Researchers have genetically fingerprinted healthy sperm1. Comparing this with faulty sperm may lead to new diagnostic tests for infertility.
Using a technique called microarray analysis, Stephen Krawetz from Wayne State University School of Medicine in Detroit, Michigan, and colleagues have found 3,000 different messenger RNAs in healthy sperm. These 'mRNAs' are the intermediaries that are produced when DNA is used to make proteins.
The researchers hope that their mRNA 'gold standard' for healthy sperm could be compared with genetic fingerprints from men with fertility problems to help identify the defective genes that lead to infertility. Some 7-10% of men are infertile.
"Looking for Mr Right's right sperm just got easier," says Gerald Schatten of Pittsburgh University School of Medicine, Pennsylvania, who studies human reproduction and development. The fingerprinting works with ejaculate, so it opens the way for automated, non-invasive analyses of sperm viability, he says. "These mRNAs may become invaluable."
Until recently, the best way to identify healthy sperm was to look at their speed and shape. But assisted-reproduction techniques such as intracytoplasmic sperm injection, in which single sperm are manually injected into eggs, have rendered such sperm assays almost obsolete, says Schatten, because they work even with sperm of abnormal appearance.
Assisted-reproduction pioneer Robert Winston of Imperial College, London, is more cautious: "Microarray analysis won't be immediately applicable to sperm analysis - it will be a long time before it replaces conventional analysis."
What does Daddy do?
“It will be a long-time before microarray analysis replaces conventional analysis Lord Robert Winston , Imperial College, London”
Some of the 3,000 mRNAs code for proteins that are essential for the early development of the embryo. This is intriguing, says Krawetz. Beyond contributing the paternal genome, sperm were thought to carry little more than chromosome middles and the calcium spark that activates the egg.
The mRNAs may also explain the ill-health of cloned embryos. Clones lack paternal input - a cell nucleus is injected into an egg that has been emptied of its nucleus. Says Schatten: "If we could identify these vital mRNAs, we could add them to give more viable clones."
The new work could yield other benefits. Men's sperm counts are declining in some parts of the world. Whether environmental factors are the culprits is controversial. One of the study team, David Dix of the US Environmental Protection Agency in North Carolina is already using the sperm fingerprint to find out.
He is looking at whether chemicals that disrupt our hormones, such as the by-products of water purification and agricultural pesticides, affect sperm health.
Ostermeier, G.C. Dix, D.J., Miller, D, Khatri, P. & Krawetz, S.A. Spermatozoal RNA profiles of normal fertile men. The Lancet, 360, 772 - 777, (2002).
Imperial College, London