Grant: Discovery Grants Program - Individual

Two of the most intriguing mysteries in reproductive biology are the persistence among species of an elaborate accessory gland system in males and the phenomenon of copulation-induced ovulation in females. Our discoveries about an ovulation-inducing factor (OIF) in seminal plasma provide at least one explanation that links these phenomena together. The existence of an OIF in seminal plasma, detected in every mammalian species examined so far, has broad implications and immediately evokes questions about identity, tissue sources, mechanism of action, role among species, and relevance to fertility. Most of these questions remain unanswered. In a series of pioneering studies, we have documented that OIF exists in the semen of males and influences ovarian function in females of both spontaneous ovulators (e.g., cattle) and induced ovulators (e.g., llamas and alpacas), OIF in seminal plasma induces ovulation via an endocrine route (through the blood stream) in the female, and has a dose-dependent effect at quantities as small as that present in 1/100th of an ejaculate. We discovered that OIF in seminal fluid is identical to nerve growth factor (NGF) a factor previously associated with promoting growth and development of nerves. Importantly, it is present in greater quantities in seminal plasma than in any other body fluid. The long-term objective of the research program is to shed new light on mechanisms controlling induced and spontaneous ovulation among mammalian species. The short-term objectives are focused on 1) the form in which OIF is secreted into the seminal plasma in males, and how this form influences the transport and availability at target tissues in the female, 2) the primary sites of action of OIF in the female and the mechanism by which OIF signals the ovulatory response in the brain, 3) the pre- and post-pubertal developmental progression of the OIF system in induced ovulators, and 4) the potential of using OIF abundance as a marker for male fertility and relatedness among different species of induced ovulators. The discovery of OIF has opened an entirely new area of research about mechanisms controlling ovulation and future discoveries will unveil the mysterious connection between the constituents of semen in the male and the phenomenon of ovulation in the female.