Faulty immune cells that normally help sperm mature seem to determine whether a man will be fertile or not, suggests a new study by researchers at The Feinstein Institute for Medical Research. Researcher Yousef Al-Abed said his study focused on an immune substance called macrophage migration inhibitory factor (MIF), which is found in semen and is key to helping sperm mature.
Al-Abed collected semen samples from both fertile and infertile men and found that those men with infertility problems had MIF levels that were either too high or too low. Those who had no problems conceiving had levels that were normal. Tellingly, when the researchers added MIF into lab dishes filled with healthy sperm, it decreased the count and impaired their motility significantly.
MIF is known to be a key player in the immune system. It was identified 40 years ago but it was only recently that scientists discovered its role as a pro-inflammatory substance. MIF has now been linked to many autoimmune and inflammatory diseases - such as diabetes and sepsis - and Al-Abed has been trying to identify and design small molecules that would block MIF activity.
Writing about MIF in Molecular Medicine, the Feinstein researchers said they had identified a critical area on the MIF protein surface that is crucial for the inflammatory response. A substance designed to target this area could be used to treat a variety of conditions, including septic shock, sepsis, rheumatoid arthritis, diabetes and male infertility. In an animal model of sepsis, a specific inhibitor called ISO-1 abolished MIF's potent inflammatory abilities and the animals responded dramatically.
MIF levels are also two times higher in autoimmune diseases like rheumatoid arthritis and diabetes. In the laboratory, Al-Abed and his colleagues found that having MIF on board in high amounts in animals prone to diabetes set the disease process in motion weeks earlier than expected. The team is now trying to design a clinical study to look at MIF levels in type 1 (juvenile) diabetes.
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Source: North Shore-Long Island Jewish Health System