Abstract
Oleic acid protects oocytes against the detrimental effects of saturated free fatty acids During the last four decades, the fertility of high-producing dairy cows has declined dramatically. This decline in fertility has been linked to the equally marked increase in milk production, and the consequent more severe negative energy balance
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(NEB) that dairy cows experience during the early post-partum period. This NEB results from the high energy costs of milk production, which cannot be compensated by energy intake from food in the initial weeks after calving. A major metabolic characteristic of a NEB is an elevation in free fatty acid (FFA) concentrations in the blood, due to the mobilization of body fat reserves. The released FFAs serve as an alternative energy supply for aerobically functional tissues. However, marked elevations of the saturated FFA level in particular can become toxic to these tissues. In this thesis the impact of an elevated level of FFAs on the bovine oocyte and its immediate microenvironment was investigated, as the potential link between NEB and reduced fertility. The three dominating FFAs in blood and follicular fluid were the saturated palmitic and stearic acids, and mono-unsaturated oleic acid. Elevated levels of the two saturated FFAs had detrimental effects on the in vitro developmental competence of maturing oocytes, as evidenced by inhibited blastocyst formation. By contrast, the mono-unsaturated FFA was harmless to oocytes. Interestingly, the mono-unsaturated oleic acid also prevented the negative impact of the saturated FFAs on oocyte developmental competence. Remarkably, oocytes exposed to a nearly two-fold increase of the FFA concentration in follicular fluid during maturation in vivo, triggered by inducing metabolic stress in non-pregnant cows by restricted feeding, did not show any signs of reduced developmental competence. The follicular fluid appeared to have a relatively high oleic acid, but low stearic acid, content in comparison to blood; moreover, the cumulus cells that surround the oocyte incorporated, and thereby effectively sequestered, large amounts of the FFAs into their lipid droplets. Stimulating FFA storage is a protective mechanism by which oleic acid is known to help prevent lipotoxic effects on somatic cell types like skeletal muscle. The combination of a relatively high oleic acid concentration in follicular fluid, and the capacity of the surrounding cumulus cell layer to store FFAs, appears to protect the oocyte against lipotoxicity. In conclusion, elevated levels of saturated FFAs can have lipotoxic effects on the maturing oocyte; however, lipotoxicity is prevented by oleic acid and the cumulus cells that surround the oocyte. The protective environment provided by follicular fluid and the multiple cumulus cell layers surrounding the oocyte are absent during early follicular growth. Future research should examine whether elevated levels of FFAs are lipotoxic to oocytes during the early stages of follicular development.
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