Over-nutrition and obesity during pregnancy are known to result in lasting developmental and metabolic consequences in offspring. Here, using the Blobby mouse model for obesity, Rebecca Robker and co-workers (p. ) probe the mechanistic origins of these changes and test if they are reversible. They demonstrate that obese females produce cumulus oocyte complexes that exhibit changes in gene and protein expression associated with ER stress. They further show that oocytes from obese mice contain normal levels of mitochondrial (mt) DNA, but display reduced mitochondrial membrane potential and higher levels of autophagy compared with control oocytes. Following in vitro fertilization, the oocytes from obese mice form blastocysts that contain reduced levels of mtDNA and exhibit reduced developmental potential. When transferred to normal-weight surrogates, these blastocysts give rise to foetuses that are heavier than controls and exhibit reduced mtDNA content in the kidney and liver. Importantly, many of these obesity-dependent changes in oocyte characteristics and developmental potential can be reversed by treatment with ER stress inhibitors. Together, these studies demonstrate that obesity induces mitochondrial dysfunction that is transmitted to offspring, and that these defects can be alleviated by using interventions prior to conception to improve embryo and foetal development.
