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Is There Money in Sperm Proteomics? Study Shows Proteins Could Affect Fertility in Bulls

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Researchers at Pennsylvania State University are investigating whether four proteins discovered via proteomic techniques can improve the fertility of commercial dairy bulls used to inseminate tens of thousands of cows throughout their lifetime.

The study is noteworthy because bull semen is very lucrative. One bull is capable of generating thousands of dollars per week for its bovine artificial insemination company, and if its fertility can be increased by even a few percent, that would represent more dollars.

"One day we were talking to an owner of one of the artificial insemination companies, and they told us that if we can increase the fertility of those bulls by 2 percent, then they will [use the technology], because there are so many cows inseminated and so many [semen] samples sold, that if you increase the fertility by even 5 or 2 percent, that can generate a lot of money," said Arlindo Moura, the leader of a study published in the Nov. 8 online issue of the Journal of Andrology that describes how the proteins were discovered.

The researchers are collaborating with the bovine artificial insemination company Genex Cooperative to test one of their proteins in a study that involves more than 40,000 cows. In addition, they are doing laboratory studies on all four proteins to see if they increase fertility rates in vitro.

The proteins — osteopontin, spermadhesin Z13, phospholipase A2 and BSP-30 — are being added to semen samples. Researchers will then test whether or not the modified semen is more fertile.


"Some bulls generate millions of dollars throughout their lifetime," said Moura. "One time I went to a [bovine artificial insemination] company in New York, and the guy told me if he was going to give me 0.25 milliliter samples of raw semen from 16 bulls, it would cost $15,000 per week."

To find the proteins, the researchers used 2D gels and Bio-Rad's PDQuest software to compare the proteomes of commercial dairy bulls from Genex that scored differently on fertility rates. They found that certain spots were significantly associated with higher fertility.

The researchers then isolated proteins from the gel spots and analyzed them using liquid chromatography followed by tandem mass spectrometry. They found that osteopontin and phosopholipase A2 were expressed more in bulls that were more fertile, while spermadhesin Z13 was expressed less. BSP-30 tended to show either a positive or negative association with fertility. When plotted on a quadratic curve, those associations were significant.

"We wanted to identify proteins in a way that would be affordable and fast," said Moura, who is a visiting professor at Pennsylvania State University. "That's when proteomics came in handy."

One of the fertility-associated proteins — osteopontin — has already been patented by Moura's colleague, Gary Killian, based on previous preliminary results that showed that the protein increased fertility. In addition, there are two or three additional patents covering proteins that promise to increase fertility in bulls, Moura said.

"There's a race out there," said Moura. "People are trying to get these patents and to make them work."

One of the other fertility proteins that has been patented was originally discovered in chicken.

"They found out during in vitro studies that a certain protein helped with the fertilization of chickens, so they constructed a synthetic peptide that would represent a piece of that protein, and they started to add that peptide to the semen samples of bulls," said Moura. "They then did some in vitro studies and found them to be positive" for increasing fertility in bulls.

The main reason that people are rushing to discover fertility factors for bulls is that the bulls' semen is very lucrative, Moura said.

"Some bulls generate millions of dollars throughout their lifetime," said Moura. "One time I went to a [bovine artificial insemination] company in New York, and the guy told me if he was going to give me 0.25 milliliter samples of raw semen from 16 bulls, it would cost $15,000 per week."

A single bull ejaculate is usually diluted, fractionated, and delivered to farmers in thin, 15-cm-long straws, Moura explained. Each straw costs between $10 and $25 and contains thousands to hundreds of thousands of sperm cells, depending on the procedures of the insemination company.

One commercial dairy bull's semen can impregnate 50,000 to 70,000 cows in its lifetime, Moura said. Semen is usually collected from the bulls about three times a week.

Moura noted that there are also similar proteomic studies being done to try to find proteins associated with fertility in humans. However, the studies are less precise because humans do not have fertility indexes, and data is limited to men who have come to clinics either to donate sperm or to deal with problems with sperm quality.

Even if proteins are discovered that are significantly correlated with fertility in humans, it would be difficult to proceed because the US Food and Drug Administration would not look favorably on adding something to sperm that might affect the development of an embryo, Moura said.

"It would be a big thing," said Moura. "But if someone could come up with [fertility] proteins to be used in humans, it could generate a lot of money."

— Tien-Shun Lee ([email protected])

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