HEALTH NEWS

Study Title:

DHA, Sperm Quality and Fertility

Study Abstract

An omega-3 fatty acid, docosahexaenoic acid (DHA), is enriched in testicular membrane phospholipids, but its function is not well understood. The Fads2 gene encodes an enzyme required for the endogenous synthesis of DHA. Using Fads2-null mice (Fads2−/−), we found in our preceding studies that DHA deficiency caused the arrest of spermiogenesis and male infertility, both of which were reversed by dietary DHA. In this study, we investigated a cellular mechanism underlying the DHA essentiality in spermiogenesis. Periodic acid-Schiff staining and acrosin immunohistochemistry revealed the absence of acrosomes in Fads2−/− round spermatids. Acrosin, an acrosomal marker, was scattered throughout the cytoplasm of the Fads2−/− spermatids, and electron microscopy showed that proacrosomal granules were formed on the trans-face of the Golgi. However, excessive endoplasmic reticulum and vesicles were present on the cis-face of the Golgi in Fads2−/− spermatids. The presence of proacrosomal vesicles but lack of a developed acrosome in Fads2−/− spermatids suggested failed vesicle fusion. Syntaxin 2, a protein involved in vesicle fusion, colocalized with acrosin in the acrosome of wild-type mice. In contrast, syntaxin 2 remained scattered in reticular structures and showed no extensive colocalization with acrosin in the Fads2−/− spermatids, suggesting failed fusion with acrosin-containing vesicles or failed transport and release of syntaxin 2 vesicles from Golgi. Dietary supplementation of DHA in Fads2−/− mice restored an intact acrosome. In conclusion, acrosome biogenesis under DHA deficiency is halted after release of proacrosomal granules. Misplaced syntaxin 2 suggests an essential role of DHA in proper delivery of membrane proteins required for proacrosomal vesicle fusion.

From press release:

Who knew that male fertility depends on sperm-cell architecture? A University of Illinois study reports that a certain omega-3 fatty acid is necessary to construct the arch that turns a round, immature sperm cell into a pointy-headed super swimmer with an extra long tail.


"Normal sperm cells contain an arc-like structure called the acrosome that is critical in fertilization because it houses, organizes, and concentrates a variety of enzymes that sperm use to penetrate an egg," said Manabu Nakamura, a U of I associate professor of biochemical and molecular nutrition.

The study shows for the first time that docosahexaenoic acid (DHA) is essential in fusing the building blocks of the acrosome together. "Without DHA, this vital structure doesn't form and sperm cells don't work," said Timothy Abbott, a doctoral student who co-authored the study.

Men concerned about their fertility may wonder what foods contain DHA. Marine fish, such as salmon or tuna, are excellent sources of this omega-3 fatty acid.

The scientists became intrigued with DHA's role in creating healthy sperm when they experimented with "knockout" mice that lack a gene essential to its synthesis. "We looked at sperm count, shape, and motility, and tested the breeding success rate. The male mice that lacked DHA were basically infertile," Nakamura said.

But when DHA was introduced into the mice's diet, fertility was completely restored. "It was very striking. When we fed the mice DHA, all these abnormalities were prevented," he said.

The scientists then used confocal laser scanning (3D) microscopy to look at thin slices of tissue in progressive stages of a sperm cell's development. By labeling enzymes with fluorescence, they could track their location in a cell.

"We could see that the acrosome is constructed when small vesicles containing enzymes fuse together in an arc. But that fusion doesn't happen without DHA," he said.

In the absence of DHA, the vesicles are formed but they don't come together to make the arch that is so important in sperm cell structure, he noted.

Nakamura finds the role this omega-3 fatty acid plays in membrane fusion particularly exciting. Because DHA is abundant in specific tissues, including the brain and the retina as well as the testes, the scientists believe their research findings could also impact research relating to brain function and vision.

"It's logical to hypothesize that DHA is involved in vesicle fusion elsewhere in the body, and because the brain contains so much of it, we wonder if deficiencies could play a role, for example, in the development of dementia. Any communication between neurons in the brain involves vesicle fusion," he noted.

The Illinois scientists will continue to study sperm; meanwhile, Nakamura has sent some of his DHA-deficient knockout mice to other laboratories where scientists are studying DHA function in the brain and the retina.

Study Information

M. Roqueta-Rivera, T. L. Abbott, M. Sivaguru, R. A. Hess, M. T. Nakamura.
Deficiency in the Omega-3 Fatty Acid Pathway Results in Failure of Acrosome Biogenesis in Mice
Biology of Reproduction
2011 October
University of Illinois College of Agricultural, Consumer and Environmental Sciences.