title: 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.
authors.affiliation: Division of Reproduction and Endocrinology, King's College London, London, United Kingdom. ni4@sanger.ac.uk
authors.forename: Natalia
authors.initials: N
authors.lastname: Igosheva
authors.forename: Andrey Y
authors.initials: AY
authors.lastname: Abramov
authors.forename: Lucilla
authors.initials: L
authors.lastname: Poston
authors.forename: Judith J
authors.initials: JJ
authors.lastname: Eckert
authors.forename: Tom P
authors.initials: TP
authors.lastname: Fleming
authors.forename: Michael R
authors.initials: MR
authors.lastname: Duchen
authors.forename: Josie
authors.initials: J
authors.lastname: McConnell
mesh_terms: D000818:Animals; D004032:Diet / Q000009:adverse effects*; D047108:Embryonic Development; D005260:Female; D005298:Fertility; D006801:Humans; D039382:Maternal Nutritional Physiological Phenomena; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D023421:Models, Animal; D009035:Mothers; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011247:Pregnancy; D012098:Reproduction; D015053:Zygote / Q000378:metabolism*
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