Ovulation-inducing factor in semen: Implications for mammalian fertility

生殖生物学中最耐人寻味的两个谜团是雄性物种之间复杂的附腺系统的持续存在和雌性交配诱导排卵的现象。我们关于精浆中一种排卵诱导因子(OIF)的发现至少提供了一种将这些现象联系在一起的解释。到目前为止，在所有被检查的哺乳动物物种中都检测到了精浆中OIF的存在，这具有广泛的意义，并立即引发了关于身份、组织来源、作用机制、物种之间的角色以及与生育能力的相关性等问题。这些问题中的大多数仍然没有得到回答。在一系列开创性的研究中，我们已经证明OIF存在于男性的精液中，并影响女性的卵巢功能，无论是自发排卵者(如牛)还是诱导排卵者(如骆驼和羊驼)，精浆中的OIF通过内分泌途径(通过血液)在女性体内诱导排卵，并具有剂量依赖效应，仅为射精的1/100。我们发现精液中的OIF与神经生长因子(NGF)相同，NGF以前与促进神经生长和发育有关。重要的是，它在精浆中的含量比在任何其他体液中都要多。该研究计划的长期目标是为哺乳动物物种的诱导和自发排卵控制机制提供新的线索。短期目标集中在1)OIF分泌到男性精浆中的形式，以及这种形式如何影响女性目标组织的运输和可用性，2)OIF在女性中的主要作用部位和OIF在大脑中发出排卵反应信号的机制，3)诱导排卵者OIF系统在青春期前后的发育过程，以及4)利用OIF丰度作为男性生育能力和不同种类诱导排卵者之间亲缘关系的标记的可能性。OIF的发现开启了控制排卵机制的全新研究领域，未来的发现将揭示男性精液成分与女性排卵现象之间的神秘联系。

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.