Ovulation-inducing factor: implications for mammalian fertility

排卵是所有哺乳动物生殖过程中的一个基本事件。排卵失败或排卵不及时对生育有深远的影响。来自申请人实验室的令人兴奋的数据现在对引起排卵级联的因素有了新的认识。研究结果证明了精浆中存在一种新的排卵诱导因子（OIF），并为OIF作为一种控制排卵时间的机制在哺乳动物物种中广泛保守的假设提供了理论依据。哺乳动物的排卵可分为诱导排卵（即由交配刺激引起的）和自发排卵（即由内源性内分泌节律引起的）。然而，在诱导排卵和自发排卵的极端之间存在一个系统发育连续体，并且一些机制对两者都是共同的。在一系列开创性的研究中，我们最近记录了：1)在骆驼、羊驼（均为诱导排卵者）和牛（均为自发排卵者）的精浆中存在一种分子量相对较大的蛋白（>30 kD），能够诱导排卵；2)精浆中的OIF通过全身而非局部途径起作用；3)精浆中OIF是促黄体生成素释放的有效刺激物；4) oif诱导的循环LH升高与黄体发育和分泌增强有关。在诱导排卵和自发排卵的代表中发现OIF是新颖的，对所有物种生育的科学理解具有广泛的意义。本研究的具体目标是：1)分离、纯化和表征OIF的生化组成；2)确定OIF在物种间的保守程度；3)确定OIF在促排卵和黄体形成中的作用机制；4)确定OIF的组织来源。精液中排卵诱导因子的表征将对所有哺乳动物的排卵过程的传统概念产生深远的影响，并从根本上挑战。这项研究的一个重要应用将涉及诊断先前未知的男性和女性因素不育的原因，以及开发改善或预防受孕的替代方法。

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.