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

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.