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: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=527211
• 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.

在未来20 - 25年内，全球对动物蛋白的需求将大大增加。因此，提高食用动物生产率的效率至关重要。公牛的生育能力或其冷冻精液是牛生产的主要决定因素。微观镜面上精子的结构和功能的变化（常规精液评估期间无法检测到）会影响牛的生育能力。关于精子发育的分子基础（精子发生）和精子功能的越来越多的知识将对改善牛的生育预测产生影响。该建议基于以下一般假设：从同一公牛获得的形态正常与严重异常的精子（具有独特的功能障碍）的比较将是实现这一目标的合适方法。睾丸体温调节的任何破坏都会引起异常的精子产生。基于这一原则，我们最近使用阴囊绝缘材料损害了公牛的精子产生，并且我们从同一公牛中恢复了正常的（绝缘）与异常的精子（与使用实验室动物相比，该模型的独特优势）。在使用这些精子的初步研究中，我们鉴定了一种参与精子功能调节的新分子（Na+/K+ATPase的睾丸特异性同工型），清楚地证明了该模型在配子生物学中创造新知识的潜力。当前的建议是这项研究的延续，并专注于研究吡咯精子的发育和功能受损的分子基础（梨形精子；不育公牛最常见的精子异常）。我希望这项研究将增加有关精子发生，精子功能调节的知识以及对早期胚胎发育的精子的贡献，这是我研究的长期目标。在应用水平上，这项研究可以鉴定出生育能力的分子标志物，这对提高动物生产力和理解男性因素不育症的重要意义。此外，该研究计划将培训高素质的学术界和行业。