Oxidative Shielding of Sperm and Inter-generational Costs of Reproduction in a Wild African Mammal

野生非洲哺乳动物精子的氧化屏蔽和代际繁殖成本

• 批准号: 2254823
• 金额: --
• 依托单位: UNIVERSITY OF EXETER
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2254823
• 关键词: Oxidative; Shielding; Sperm; Inter; generational

High investment in reproduction can decrease survival, and future reproductive success. This so-called 'cost of reproduction' is thought to be mediated by oxidative stress, where reactive oxygen species (ROS) arising as a by-product of metabolic activity overwhelm the body's antioxidant defences, and cause serious damage to DNA, proteins and lipids. We recently proposed a new perspective on the cost of reproduction: the potential for parents' oxidative state to impact on their physiologically-dependent offspring. In mothers, oxidative stress may have such inter-generational impacts by damaging DNA in the ova, and by impairing placental function and milk quality. Mothers should therefore be selected to minimise such damage transmission (the 'oxidative shielding' hypothesis). We are currently studying such mother-offspring impacts as part of a large NERC-funded project using wild banded mongooses living at Queen Elizabeth National Park in Uganda (www.bandedmongoose.org).Oxidative shielding is likely to be similarly important for fathers. Oxidative stress may cause DNA damage in sperm, which reduces fertility, but may also impair offspring development and survival1. The proposed PhD studentship will assess for the first time how oxidative state in fathers can have inter-generational impacts. The successful candidate will combine fieldwork in Africa, behavioural observations, cutting-edge physiological assays and longitudinal data analysis to advance fundamental understanding of life history evolution.Sperm are extremely susceptible to oxidative damage, being richly endowed with polyunsaturated fatty acids, while having deficient damage detection and repair mechanisms. Such oxidative damage can impair fertilization capacity, and contribute to DNA damage including chromosomal aberrations, epigenetic modifications, mutations, base oxidation and sperm DNA fragmentation, all of which may reduce reproductive success and impose inter-generational impacts on offspring. Males may be able to modulate this risk by investing more into antioxidant defence of sperm during reproductively active periods1. Indeed, we recently reported that blood levels of vitamin E increase sharply during breeding in male banded mongooses, although the consequences for sperm DNA damage, fertility, and offspring growth and survival await study. The over-arching aim of this PhD studentship is to test the oxidative shielding hypothesis in male banded mongooses at our Uganda field site. The population has been studied for the last 25 years, and individuals are routinely monitored from birth to death including detailed observations of reproductive investment, offspring development and survival. Blood samples are collected at regular intervals over the life course, in order to assign parentage to pups, and to enable measurements of oxidative stress. It is also possible to experimentally manipulate nutritional condition, in order to examine effects on oxidative state and 'shielding' of sperm. The studentship will address the following questions:1. Does variation in males' oxidative state influence DNA damage in sperm, and fertility?2. Does sperm DNA damage negatively impact on pup growth, development and survival, and future reproductive success? Full life history records are collected by detailed behavioural observations. Sperm will be collected by electro-ejaculation. Markers of oxidative state (oxidative damage, and a range of antioxidants) are measured using established techniques such as HPLC. DNA damage will be measured in terms of 8-hydroxy-2'-deoxyguanosine (8-OHdG) using EIA.

对繁殖的高投资会降低存活率和未来的繁殖成功率。这种所谓的“繁殖成本”被认为是由氧化应激介导的，其中作为代谢活动的副产品产生的活性氧（ROS）压倒了身体的抗氧化防御，并对DNA，蛋白质和脂质造成严重损害。我们最近提出了一个关于繁殖成本的新观点：父母的氧化状态可能会影响他们生理上依赖的后代。在母亲中，氧化应激可能会通过破坏卵子中的DNA以及损害胎盘功能和牛奶质量而产生这种代际影响。因此，应该选择母亲来尽量减少这种损害传播（“氧化屏蔽”假设）。目前，我们正在研究这种母子关系的影响，作为NERC资助的一个大型项目的一部分，使用生活在乌干达伊丽莎白女王国家公园的野生带状猫鼬（www.bandedmongoose.org）。氧化应激可能导致精子中的DNA损伤，从而降低生育能力，但也可能损害后代的发育和存活1。拟议的博士生奖学金将首次评估父亲的氧化状态如何产生代际影响。成功的候选人将结合联合收割机在非洲的实地考察，行为观察，尖端的生理测定和纵向数据分析，以推进对生命史进化的基本理解。精子极易受到氧化损伤，被赋予丰富的多不饱和脂肪酸，同时缺乏损伤检测和修复机制。这种氧化损伤会损害受精能力，并导致DNA损伤，包括染色体畸变、表观遗传修饰、突变、碱基氧化和精子DNA片段化，所有这些都可能降低生殖成功率并对后代造成代际影响。男性可能能够通过在生殖活跃期对精子的抗氧化防御进行更多投资来调节这种风险。事实上，我们最近报告说，在雄性带状猫鼬的繁殖过程中，维生素E的血液水平急剧增加，尽管精子DNA损伤，生育力和后代生长和存活的后果有待研究。这个博士研究生项目的主要目的是在我们乌干达实地考察的雄性带状猫鼬中检验氧化屏蔽假说。在过去的25年里，人们一直在研究这个种群，从出生到死亡，对个体进行常规监测，包括详细观察生殖投资、后代发育和存活。在整个生命过程中定期收集血液样本，以便为幼仔分配亲子关系，并能够测量氧化应激。还可以通过实验操纵营养条件，以检查对精子氧化状态和“屏蔽”的影响。 该奖学金将解决以下问题：1。男性氧化状态的变化是否会影响精子中的DNA损伤和生育能力？2.精子DNA损伤是否会对幼犬的生长、发育和存活以及未来的繁殖成功产生负面影响？通过详细的行为观察收集完整的生活史记录。将通过电射精收集精子。氧化状态的标志物（氧化损伤和一系列抗氧化剂）使用已建立的技术（如HPLC）进行测量。使用EIA以8-羟基-2 '-脱氧鸟苷（8-OHdG）测量DNA损伤。