“In our experiment, we used ‘knockout’ mice that lacked the gene responsible for an enzyme important in making docosahexaenoic acid (DHA). In the absence of DHA, male mice are basically infertile, producing few if any misshaped sperm that can’t get where they need to go,” said Manabu Nakamura, a U of I associate professor of food science and human nutrition.
“We looked at sperm count, shape, and motility and tested the breeding success rate, and the mice lacking DHA simply were not able to breed,” said Manuel Roqueta-Rivera, a U of I doctoral student who also worked on the study.
In the DHA-deficient knockout mice, sperm counts were extremely low. The sperm that were produced were round instead of elongated and they were unable to move well, he said.
But, when DHA was introduced into the diet, fertility was completely restored. “It was very striking. When we fed the mice DHA, all these abnormalities were prevented,” he said.
This is the first time that the importance of DHA to male fertility has been shown this directly, although some studies have suggested that male fertility patients with low sperm counts and less motile sperm tend to have low levels of this fatty acid.
The DHA study is part of the Nakamura team’s efforts to understand the function of the omega-3 and -6 fatty acids. As part of that work, they have developed a mouse model to help them understand a particular fat’s physiological role. By knocking out genes, they can create deficiencies of the fats they are interested in and learn about their functions.
“Knocking out the gene for the delta-6-desaturase enzyme has led to some surprising discoveries, including this one about the importance of DHA in sperm formation and mobility,” he said.
Nakamura said our body must make DHA from dietary alpha-linolenic acids, the parent compound of the omega-3 fatty acid family. Vegetable oils, including soybean and canola oil, are good sources of alpha-linolenic acid.
Nakamura’s team plans to continue focusing on this omega-3’s effects on fertility. But he cautioned that there are still things they don’t understand.
“We get hints from looking at sperm in the DHA-deficient animals about what type of pathology we may be looking at and why these polyunsaturated fatty acids are important. But we’re still at the starting point in understanding the mechanisms that are involved, and we need to do more research at the cellular level,” he said.
The study was published in the February issue of the Journal of Lipid Research. Co-authors with Roqueta-Rivera and Nakamura are Chad K. Stroud, Wanda M. Haschek, Sandeep J. Akare, Mariangela Segre, and Rex A. Hess, all of the U of I, and Richard S. Brush, Martin-Paul Agbaga, and Robert E. Anderson, all of the University of Oklahoma Health Sciences Center.
Funding was provided in part by a CONACyT Mexico fellowship award, grants from the National Institutes of Health, the Foundation Fighting Blindness, and Research to Prevent Blindness.
University of Illinois at Urbana-Champaign