Microbiology/Genetics

What Dictates Male Fertility?

An immune factor

By Stefan Anitei, Science Editor

2nd of July 2007, 19:06 GMT

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It is easy to blame it on the woman, but in 40 % of the couples, the man is the sterile part. Now, a team at the Feinstein Institute for Medical Research found an immune factor that regulates human semen, inducing fertility or sterility in a man.

The macrophage migration inhibitory factor (MIF) appears to be crucial in maturing sperm, to make it ready for reproduction. This discovery could lead to a new test for male fertility. The team collected semen samples from men three to five days after a sexual abstinence period.

The research pool

was made of 68 men with reproductive issues and 27 healthy controls, and the analyses were made without the identity of the owner being known. The individuals with infertility issues presented too high or too low MIF levels, while the healthy subjects had average values.

When supplementary MIF was added into lab dishes with normal sperm, their count and mobility dropped. In this case, MIF could be employed as a method of male contraception. The team has also developed a patent that can be employed to analyze MIF levels in order to forecast a man's fertility.

MIF is a crucial immune molecule, detected 40 years ago, and only recently found to be a pro-inflammatory chemical. It has been connected to many autoimmune and inflammatory conditions, like diabetes and sepsis. The Feinstein team recently discovered a critical zone on the MIF protein surface that induces the main inflammatory response. A chemical attacking that area could be employed to treat many conditions, such as septic shock, sepsis, rheumatoid arthritis and diabetes.

They developed a specific inhibitor, ISO-1, to match the pro-inflammatory area. In animal tests with sepsis, ISO-1 kills MIF's potent inflammatory capacities and the animals survived with a once-fatal sepsis. In case of sepsis (an over-reactive and usually deadly immune response to a bacterial attack) MIF levels are 10 to 20 times over the normal. If MIF decreases, the patients' survival chances increase dramatically.

215,000 Americans die annually of sepsis, while another 500,000 survive the infection, but often with severe cardiovascular problems. MIF was found crucial in heart damage. The anti-MIF antibodies significantly increased cardiac performance during septic shock. MIF levels are also two times higher in autoimmune conditions like rheumatoid arthritis and diabetes.

The research team discovered that having high levels of MIF makes lab animals prone to diabetes, weeks earlier than expected. But MIF does not work by itself: it uses a network of molecules to trigger its pro-inflammatory effects. The Feinstein team aims to detect those recruit chemicals.

TAGS:

fertility | immune | sterility

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