JULY 2014 – Dr. Nancy Brackett has been heading up the male fertility research program for over 20 years and has led the field in discoveries regarding the mechanisms underlying SCI-induced male infertility. Many years of research have revealed that SCI impairs the motility of sperm. There are altered levels of inflammatory chemicals in the seminal fluid after SCI. These chemicals are present at high enough levels that they become toxic to sperm; they do not kill the sperm, but they reduce the motility to significantly impair the likelihood of fertilization. There is growing knowledge that these inflammatory chemicals get turned on by the inflammasome, which is a multi-protein complex that activates inflammatory processes. A couple of years ago, Dr. Brackett and her research team demonstrated that a technique can be used to neutralize these inflammatory chemicals when the sperm sample is in a Petri dish. This resulted in increased motility of the sperm in the dish. However, it still required the use of assistive reproductive techniques for successful fertilization. It also did not get at the trigger of whatever is activating the inflammasome.
Last year Dr. Brackett was awarded a grant from the Craig H. Nielsen Foundation to further our understanding of the biology behind these elevated inflammatory chemicals and test a medication that can be taken by mouth to try to neutralize them. The medication is a known inhibitor of a key protein (pannexin-1) involved in the activation of inflammasomes. The main objective of the grant is to determine if pannexin-1 contributes to impaired sperm motility associated with SCI. This will be tested in 3 ways.
1. They will determine the protein levels and the cellular distribution of pannexin-1 in the semen of men with SCI versus age-matched non-injured control subjects. This will let them know if SCI causes an increase in pannexin-1 expression or changes its distribution pattern within cells so that it can become more active. If pannexin-1 is more active, it can activate inflammasomes.
2. They will determine if inhibition of inflammasome activation by blocking pannexin-1 with the medication in a Petri dish results in improved sperm motility in men with SCI.
3. They will determine if taking the medication orally will result in ejaculated semen with improved sperm motility in men with SCI. The team is about halfway through with the experiments and Dr. Brackett has presented preliminary results at two meetings of the American Urological Association. If oral administration of the medication is safe and results in improved semen quality, this will decrease the need for invasive and expensive assisted reproductive technologies currently required to overcome low sperm motility and achieve pregnancy. The results are expected to lead to improved reproductive function in men with SCI and, therefore, a higher quality of life.