Protein in Semen Acts on Brain and Triggers Ovulation

A new study carried out in the August issue of the journal Proceedings of the National Academy of Science (PNAS), presents a new finding toward fertility in mammals, including humans.

An international team from the University of Saskatchewan (U of S), led by Gregg Adams, discovered that the molecule responsible for the growth, maintenance and survival of nerve cells also exists in semen. The protein, that is dubbed as the ovulation-including factor (OIF), acts on the female brain, which in turn prompts ovulation.

"From the results of our research, we now know that these glands produce large amounts of a protein that has a direct effect on the female," said Adams, a professor of veterinary biomedical sciences at the Western College of Veterinary Medicine at the U of S.

In order to discover the identity of this protein, the team carefully analyzed the OIF present in the semen of all species of mammals. The team compared the OIF of thousands of other proteins, including nerve growth factor (NGF), which is present primarily in the nerve cells throughout the body.

"To our surprise, it turns out they are the same molecule," Adams says. "Even more surprising is that the effects of NGF in the female were not recognized earlier, since it's so abundant in seminal plasma."

The mechanism of OIN/NGF is not constant in all animals. Its function is different in different animals. While conducting the study, the researchers learnt that this protein shows up in all mammals from llamas, cattle and koalas, to pigs, rabbits, mice, and humans. Its presence indicates that it plays a critical role in the reproduction of all mammals. The researchers are still trying to figure out how it works, its role in different species and how it is clinically relevant to human infertility.

OIF/NGF in the semen acts as a hormonal signal, working through the hypothalamus of the female brain and the pituitary gland. Therefore, this activates the production of other hormones that signal the ovaries to release an egg or eggs that is based on the specie it is present in.

In order to find more evidence of the link, the researchers focused on two species, namely, llamas and cattle. Llamas are induced ovulators, that is, they ovulate only when they have been inseminated. On the other hand, cows and humans are spontaneous ovulators, which means that they have a regular buildup of hormones that stimulates the release of an egg.

With the help of an innovative technique, the researchers carefully analyzed OIF and NGF, and noticed they are similar in size and have the same effect across species. The structure of the molecule was confirmed at the Canadian Light Source synchrotron at the U of S.

"The idea that a substance in mammalian semen has a direct effect on the female brain is a new one," Adams explained. "This latest finding broadens our understanding of the mechanisms that regulate ovulation and raises some intriguing questions about fertility."

This research included Marcelo Ratto and Ximena Valderrama from the Universidad Austral de Chile in Valdivia, Chile, as well as Adams, Yvonne Leduc, Karin van Straaten and Roger Pierson from the U of S. It was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC), the Alpaca Research Foundation, the Chilean National Science and Technology Research Council, the Saskatchewan Health Research Foundation, and the Canadian Institutes of Health Research (CIHR).

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