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

形态异常的牛精子：研究精子发生、精子功能和精子对植入前胚胎发育的贡献的模型

• 批准号: 341153-2009
• 负责人: Thundathil, Jacob
• 金额: $ 1.75万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2011
• 资助国家: 加拿大
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=481993
• 关键词: Morphologically; abnormal; bovine; sperm; model

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.

未来20-25年，全球对动物蛋白的需求将大幅增加。因此，提高食用动物的生产效率至关重要。公牛的生育力，或其冷冻精液，是牛产量的主要决定因素。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）影响公牛的生育能力。增加关于精子发育（精子发生）和精子功能的分子基础的知识将对提高牛的生育能力预测产生影响。这一建议是基于一个普遍的假设，即从同一头公牛获得的形态正常与严重异常精子（具有明显的功能损伤）的比较将是实现这一目标的合适方法。睾丸温度调节的任何中断都会导致精子产生异常。基于这一原理，我们最近使用阴囊绝缘来影响公牛的精子产生，我们从同一只公牛身上恢复了正常（绝缘前）和异常精子（与使用实验动物相比，该模型的独特优势）。在使用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（Na+/K+ atp酶的睾丸特异性异构体），清楚地证明了该模型在创造配子生物学新知识方面的潜力。目前的建议是该研究的延续，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。我希望通过这项研究增加对精子发生、精子功能调控以及精子对早期胚胎发育的贡献的认识，这是我研究的长期目标。在应用层面上，本研究可以识别生育的分子标记，对提高动物生产力和在跨学科水平上理解雄性因素不育具有重要意义。此外，该研究项目将为学术界和工业界培养高素质的人才。