Maternal Diet-Induced Obesity Alters Mitochondrial Activity and Redox Status in Mouse Oocytes and Zygotes

Abstract

The negative impact of obesity on reproductive success is well documented but the stages at which development of the conceptus is compromised and the mechanisms responsible for the developmental failure still remain unclear. Recent findings suggest that mitochondria may be a contributing factor. However to date no studies have directly addressed the consequences of maternal obesity on mitochondria in early embryogenesis.Using an established murine model of maternal diet induced obesity and a live cell dynamic fluorescence imaging techniques coupled with molecular biology we have investigated the underlying mechanisms of obesity-induced reduced fertility. Our study is the first to show that maternal obesity prior to conception is associated with altered mitochondria in mouse oocytes and zygotes. Specifically, maternal diet-induced obesity in mice led to an increase in mitochondrial potential, mitochondrial DNA content and biogenesis. Generation of reactive oxygen species (ROS) was raised while glutathione was depleted and the redox state became more oxidised, suggestive of oxidative stress. These altered mitochondrial properties were associated with significant developmental impairment as shown by the increased number of obese mothers who failed to support blastocyst formation compared to lean dams. We propose that compromised oocyte and early embryo mitochondrial metabolism, resulting from excessive nutrient exposure prior to and during conception, may underlie poor reproductive outcomes frequently reported in obese women.

Maternal obesity in mice not only affects fresh embryo quality but also aggravates injury due to vitrification

“…We previously found significantly reduced developmental competence and elevated apoptosis rate in DIO mouse embryos compared to the control group [18], which is consistent with previous reports [19,20]. However, we also demonstrated that the embryonic survival and developmental rate differences between obese and control mice were eliminated after embryos were vitrified and thawed, in contrast to the results in domestic animals [18].…”

The impact of obesity on egg quality

“…Mitochondria are maternally derived; so maternal nutrition could have major effects on this organelle. Their primary function is production of ATP by oxidative phosphorylation; they also development to the blastocyst stage [72].…”

Cytoplasmic Inheritance Redux

“…The oviduct is, of course, not an environment distinct from the environment of the mother's body, nor is the mother's body an environment distinct from all the environments she occupies. There is growing evidence that all these environments can impact PID with potentially lifelong consequences (Ashworth, Toma, & Hunter, 2009;Igosheva et al, 2010;Junien, 2006;Kwong, Wild, Roberts, Willis, & Fleming, 2000).…”