Purification of ovulating-inducing factor (OIF) in alpaca seminal plasma for research and product Development

Principal investigator:

Gregg P. Adams, DVM, PhD.
Western College of Veterinary Medicine
University of Saskatchewan, Canada

Publications Resulting from this Work:

Theriogenology. 2020 Jan 30. pii: S0093-691X(20)30091-1. doi: 10.1016/j.theriogenology.2020.01.078. [Epub ahead of print]

Ovulation mechanism in South American Camelids: The active role of β-NGF as the chemical signal eliciting ovulation in llamas and alpacas.

Silva M, Paiva L, Ratto MH.

Abstract

The ovulation-inducing effect of seminal plasma was first suggested in Bactrian camels over 30 years ago, initiating a long search to identify the 'ovulation-inducing factor' (OIF) present in camelids semen. During the last decade, primarily in llamas and alpacas, this molecule has been intensively studied characterizing its biological and chemical properties and ultimately identifying it as β-Nerve Growth Factor (β-NGF). The high concentration of OIF/β-NGF in seminal plasma of llamas and alpacas, and the striking effects of seminal fluid on ovarian function strongly support the notion of an endocrine mode of action. Also, have challenged the dogma of mating induced ovulation in camelid species, questioning the classical definition of reflex ovulators, which at the light of new evidence should be revised and updated. On the other hand, the presence of OIF/β-NGF and its ovulatory effect in camelids confirm the notion that seminal plasma is not only a transport and survival medium for sperm but also, a signaling agent targeting female tissues after insemination, generating relevant physiological and reproductive consequences. The presence of this molecule, conserved among induced as well as spontaneous ovulating species, clearly suggests that the potential impacts of this reproductive feature extend beyond the camelid species and may have broad implications in mammalian fertility. The aim of the present review is to provide a brief summary of all research efforts undertaken to isolate and identify the ovulation inducing factor present in the seminal plasma of camelids. Also to give an update of the current understanding of the mechanism of action of seminal β-NGF, at central and ovarian level; finally suggesting possible brain targets for this molecule.

The Nerve of Ovulation-inducing Factor in Semen

Marcelo H. Ratto, Yvonne A. Leduc, Ximena P. Valderrama, Karin E. van Straaten, Louis T. J. Delbaere, Roger A. Pierson, and Gregg P. Adams

www.pnas.org/cgi/doi/10.1073/pnas.1206273109

For a male animal to pass on his genes, he must create sperm. However, the fluid which carries sperm — semen — contains much more than just sperm cells. The surrounding seminal fluid is a complex mix of sugars, lipids, proteins and vitamins. Males require several accessory sex glands to create this soup of chemicals. The sheer complexity of semen and the presence of these sex glands had puzzled researchers for years. Some males use the chemical mix in seminal fluid to create a mating plug — a gooey clump that blocks the female's reproductive tract to prevent other males' sperm from gaining entry. However, male animals that do not use mating plugs still have functioning accessory glands, so they must serve a different function. In 1985, a group of Chinese researchers found that when camel seminal fluid was injected into female camels, they ovulated, even when no sexual activity had occurred. The researchers claimed that there was a chemical present in the fluid that stimulated ovulation. For 20 years their claim was ignored.

In 2005, Gregg Adams, a veterinarian at the University of Saskatchewan in Saskatoon, Canada, successfully repeated the Chinese experiment in llamas. He and his colleagues at the Universidad Austral de Chile in Valdivia, Chile, then spent the next seven years trying to find the mystery chemical in semen that triggered egg release. They collected and purified semen from llamas and injected various components into females to see if they would ovulate. The protein they tracked down as the one responsible for ovulation turned out to be both surprising and familiar. The stimulatory chemical is a protein called — nerve growth factor, or NGF, which had been known to function in the brain to keep neurons alive. NGF from semen appears to send signals to the female llama brain that result in ovulation. Though animal semen (including human semen) was known to be rich in NGF, no one had ever connected the protein to semen's stimulatory effect. (Currently it is unknown if the protein affects ovulation in humans.) The study was published in the Proceedings of the National Academy of Sciences August 20, 2012.