Ovulation-inducing factor in semen: Implications for mammalian fertility

我们在雄性动物的精液中发现了一种能引起雌性动物排卵反应的成分，而且迄今为止，我们在所有研究过的物种中都发现了这种成分。精浆中排卵诱导因子（OIF）的存在具有广泛的意义，并立即引发了关于其身份、组织来源、作用机制、物种间作用以及与不孕症临床相关性的问题。这些问题中的大多数仍未得到解答。哺乳动物的排卵可分为诱导排卵（由交配引起）和自发排卵（由自然荷尔蒙节律引起）。然而，存在一个连续体，一些机制对两者都是共同的。在一系列开创性的研究中，我们已经证明OIF存在于男性精液中，并影响自发排卵和诱导排卵的女性卵巢功能，精液中的OIF通过内分泌途径（通过血流）诱导女性排卵，并且在剂量小至射精的1/100时具有剂量依赖性效应。最近，我们发现精液中的OIF与神经生长因子（NGF）相同，这是一种以前与促进神经生长和发育有关的因子。重要的是，它在精浆中的含量比在任何其他体液中的含量都要高。我们研究计划的长期目标是揭示哺乳动物物种控制排卵的机制。短期目标集中在精液OIF在排卵中的作用，通过确定1)女性的作用部位（脑、垂体、卵巢），2)男性生殖组织中OIF的来源，3)精液中OIF与男性生育能力之间的关系，4)OIF对黄体的影响（支持怀孕），以及5)OIF与其他交配刺激对女性卵巢功能的相对作用。我们处于OIF研究的前沿，也处于我们对男性如何影响女性卵巢的理解转变的尖端。揭示OIF在精液中的生物学作用将对男性和女性不育症的诊断以及不育症和避孕新疗法的发展产生重要影响。

We have discovered a component in the semen of the male that elicits an ovulatory response in the female, and we have found it in every species examined thus far. The existence of an ovulation-inducing factor (OIF) in seminal plasma has broad implications and immediately evokes questions about identity, tissue sources, mechanism of action, role among species, and clinical relevance in infertility. Most of these questions remain unanswered. Ovulation in mammals may be classified as induced (elicited by mating) or spontaneous (elicited by natural hormonal rhythm). However, a continuum exists and some mechanisms are common to both. 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 and induced ovulators, OIF in seminal plasma induces ovulation via an endocrine route (through the blood stream) in the female, and has a dose-dependent effect at doses as small as that present in 1/100th of an ejaculate. Most recently, 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 our research program is to shed new light on mechanisms controlling ovulation among mammalian species. Short-term objectives are focused on the role of seminal OIF in ovulation by determining 1) the site of action in the female (brain, pituitary, ovary), 2) the source of OIF within the male reproductive tissues, 3) the relationship between OIF in semen and male fertility, 4) the effects of OIF on the corpus luteum (in support of pregnancy), and 5) the relative role of OIF vs other copulatory stimuli on ovarian function in the female. We are at the forefront of research on OIF and on the cusp of a shift in our understanding of how the male influences the ovaries of the female. Uncovering the biological role of OIF in semen will have an important impact on diagnosis of male and female infertility, and on the development of new treatments for infertility and contraception.