Study Title:

DHA Restores Fertility

Study Abstract

Delta-6 desaturase-null mice (–/–) are unable to synthesize highly unsaturated fatty acids (HUFAs): arachidonic acid (AA), docosahexaenoic acid (DHA), and n6-docosapentaenoic acid (DPAn6). The –/– males exhibit infertility and arrest of spermatogenesis at late spermiogenesis. To determine which HUFA is essential for spermiogenesis, a diet supplemented with either 0.2% (w/w) AA or DHA was fed to wild-type (+/+) and –/– males at weaning until 16 weeks of age (n = 3–5). A breeding success rate of DHA-supplemented –/– was comparable to +/+. DHA-fed –/– showed normal sperm counts and spermiogenesis. Dietary AA was less effective in restoring fertility, sperm count, and spermiogenesis than DHA. Testis fatty acid analysis showed restored DHA in DHA-fed –/–, but DPAn6 remained depleted. In AA-fed –/–, AA was restored at the +/+ level, and 22:4n6, an AA elongated product, accumulated in testis. Cholesta-3,5-diene was present in testis of +/+ and DHA-fed –/–, whereas it diminished in –/– and AA-fed –/–, suggesting impaired sterol metabolism in these groups. Expression of spermiogenesis marker genes was largely normal in all groups. In conclusion, DHA was capable of restoring all observed impairment in male reproduction, whereas 22:4n6 formed from dietary AA may act as an inferior substitute for DHA.

From press release:

According to a University of Illinois study, omega-3 fatty acids may be good for more than heart health. A little-known omega-3 may have implications for treating male infertility.

"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.

Study Information

Manuel Roqueta-Rivera, Chad K. Stroud, Wanda M. Haschek, Sandeep J. Akare, Mariangela Segre, Richard S. Brush, Martin-Paul Agbaga, Robert E. Anderson, Rex A. Hess and Manabu T. Nakamura.
Docosahexaenoic acid supplementation fully restores fertility and spermatogenesis in male delta-6 desaturase-null mice
Journal of Lipid Research
2010 February
Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801.

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