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

未来20-25年内，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。公牛的繁殖力，或它们的冷冻精液，是牛生产的一个主要决定因素。精子结构和功能在亚显微水平上的变化(在常规精液评估中无法检测到)会影响公牛的繁殖力。越来越多的关于精子发育(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预测产生影响。这一建议是基于一个普遍的假设，即比较从同一头公牛获得的形态正常和严重异常(具有明显功能障碍)的精子将是实现这一目标的合适方法。睾丸温度调节的任何破坏都会导致精子产生异常。基于这一原理，我们最近使用阴囊隔离来削弱公牛的精子产生，我们从同一头公牛身上恢复了正常(隔离前)和异常的精子(与使用实验室动物相比，这是该模型的独特优势)。在对这些精子的初步研究中，我们发现了一个参与精子功能调节的新分子(睾丸特异的Na/K ATPase亚型)，清楚地表明了该模型在创造配子生物学新知识方面的潜力。目前的建议是这项研究的继续，重点是调查梨形精子(梨形精子，不育公牛最常见的精子异常)发育和功能受损的分子基础。我希望这项研究将增加关于精子发生、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。在应用水平上，这项研究可能确定生育能力的分子标记，对提高动物生产力和在跨学科水平上理解男性因素不育症具有重要意义。此外，这项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.