Obesity-exposed oocytes accumulate and transmit damaged mitochondria due to an inability to activate mitophagy

• DOI: 10.1016/j.ydbio.2017.04.005
• Publication Date: 2017-04-21T19:02:51Z
• Authors: Anna L. Boudoures; Jessica Saben; Andrea Drury; Suzanne Scheaffer; Zeel Modi; Wendy Zhang; Kelle H. Moley
• Keywords: Membrane Potential, Mitochondrial; 0301 basic medicine; Gene Dosage; Hydrazones; Mitophagy; Antimycin A; DNA, Mitochondrial; Mitochondria; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Autophagy; Oocytes; Animals; Female; Obesity; Cells, Cultured

Mitochondria are the most prominent organelle in oocyte. Somatic cells maintain a healthy population of mitochondria by degrading damaged via mitophagy, specialized autophagy pathway. However, evidence from previous work investigating more general macroautophagy pathway oocytes suggests that mitophagy may not be active This would leave vast numbers - poised to inherited offspring vulnerable damage. Here we test hypothesis inactive oocyte underlies maternal transmission dysfunctional mitochondria. To determine whether can complete used either CCCP or AntimycinA depolarize and trigger mitophagy. After depolarization, did detect co-localization with autophagosomes mitochondrial DNA copy number remained unchanged, indicating non-functional was removed. investigate impact an absence on function, utilized vitro fertilization high fat sugar (HF/HS)-exposed oocytes, which have lower membrane potential Here, demonstrate blastocysts generated HF/HS decreased potential, metabolites involved ATP generation, accumulation PINK1, marker protein. phenotype blastocyst mirrors show exposed oocytes. Taken together, these data suggest mechanisms governing fundamentally distinct those somatic cell setting exposure contributes oocyte-to-blastocyst