Ovulation-inducing factor: implications for mammalian fertility

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Ovulation is a fundamental event in the reproductive process of all mammalian species. Ovulation failure or untimely ovulation has a profound impact on fertility. Exciting data from the applicant's laboratory has now cast new light on factors responsible for eliciting the ovulatory cascade. Results document the existence of a novel ovulation-inducing factor (OIF) in seminal plasma, and provide rationale for the hypothesis that OIF is widely conserved among mammalian species as a mechanism for controlling the timing of ovulation. Ovulation in mammals may be classified as induced (i.e., elicited by copulatory stimuli) or spontaneous (i.e., elicited by an endogenous endocrine rhythm). However, a phylogenic continuum exists between the extremes of induced and spontaneous ovulators, and some mechanisms are common to both. In a series of pioneering studies, we have recently documented: 1) the existence of a protein with a relatively large molecular weight (>30 kD) in the seminal plasma of llamas, alpacas (both induced ovulators), and cattle (a spontaneous ovulator) capable of eliciting ovulation; 2) that OIF in seminal plasma acts via a systemic rather than a local route; 3) that OIF in seminal plasma is a potent stimulator of LH release; and 4) that OIF-induced elevation of circulating LH is associated with enhanced luteal gland development and secretion. The discovery of OIF in representatives of both induced and spontaneous ovulators is novel and has broad implications on scientific understanding of fertility in all species. The specific objectives of the proposed study are to 1) isolate, purify and characterize the biochemical composition of OIF, 2) determine the extent to which OIF is conserved among species, 3) determine the mechanism of action of OIF in eliciting ovulation and luteogenesis, and 4) determine the tissue source of OIF. Characterization of an ovulation-inducing factor in semen will have a profound impact on, and fundamentally challenge, traditional concepts of the ovulatory process in all mammals. An important application of this research will involve the diagnosis of previously unknown causes of male- and female-factor infertility, and the development of alternative ways of improving or preventing conception.