Morphologically abnormal bovine sperm: A model for the study of spermatogenesis, sperm function and sperm contributions to preimplantation embryo development

未来20-25年，全球对动物蛋白的需求将大幅增加。因此，提高食用动物生产效率至关重要。公牛的生育力，或其冷冻精液，是牛生产的主要决定因素。在亚显微水平上精子结构和功能的变化（在常规精液评价中检测不到）影响公牛生育力。增加有关精子发育（精子发生）和精子功能的分子基础的知识将对改善牛的生育力预测产生影响。该建议基于以下一般假设：从同一公牛获得的形态正常精子与严重异常精子（具有明显的功能障碍）的比较将是实现该目标的合适方法。睾丸温度调节的任何中断都会导致精子产生异常。基于这一原则，我们最近使用阴囊绝缘来损害公牛的精子生产，并且我们从同一公牛中回收了正常（预绝缘）与异常精子（与使用实验室动物相比，该模型具有独特的优势）。在使用这些精子的初步研究中，我们确定了一种新的分子（睾丸特异性Na+/K+ ATP酶亚型）参与精子功能的调节，清楚地表明了这种模型在配子生物学中创造新知识的潜力。目前的建议是这项研究的继续，重点是研究梨形精子（梨形精子;不育公牛中最常见的精子异常）发育和功能受损的分子基础。我希望这项研究将增加有关精子发生，精子功能调节和精子对早期胚胎发育的贡献的知识，这是我研究的长期目标。在应用层面上，这项研究可能会确定生育力的分子标记，在跨学科水平上提高动物生产力和理解男性因素不育具有重要意义。此外，该研究计划将为学术界和工业界培养高素质的人才。

The global demand for animal proteins will substantially increase over the next 20-25 years. Therefore, improving the efficiency of food animal productivity is crucial. Fertility of bulls, or their frozen semen, is a major determinant of cattle production. Changes in the structure and function of sperm at the submicroscopical level (not detectable during routine semen evaluation) influence bull fertility. Increasing knowledge regarding the molecular basis of sperm development (spermatogenesis) and sperm function will have implications for improving fertility predictions in cattle. This proposal is based on the general hypothesis that comparison of morphologically normal versus grossly abnormal sperm (with distinct functional impairments) obtained from the same bull will be a suitable approach for accomplishing this goal. Any disruption in testicular thermoregulation induces abnormal sperm production. Based on this principle, we recently used scrotal insulation to impair sperm production in bulls, and we recovered normal (pre-insulation) versus abnormal sperm from the same bull (a unique advantage of this model compared to the use of laboratory animals). In preliminary studies using these sperm, we identified a novel molecule (testis-specific isoform of Na+/K+ATPase) involved in the regulation of sperm function, clearly demonstrating the potential of this model for creating new knowledge in gamete biology. The current proposal is a continuation of this study and is focused on investigating the molecular basis of the development and impaired function of pyriform sperm (pear-shaped sperm; the most common sperm abnormality in infertile bulls). I expect that this study will increase knowledge regarding spermatogenesis, regulation of sperm function and sperm contributions to early embryo development, which is the long-term goal of my research. At the applied level, this study may identify molecular markers of fertility, with important implications for improving animal productivity and understanding male-factor infertility at an interdisciplinary level. Moreover, this research program will train highly qualified individuals for academia and industry.