Maternal Metabolic Syndrome Programs Mitochondrial Dysfunction via Germline Changes across Three Generations.
Maternal obesity impairs offspring health, but the responsible mechanisms are not fully established. To address this question, we fed female mice a high-fat/high-sugar diet from before conception until weaning and then followed the outcomes in the next three generations of offspring, all fed a control diet. We observed that female offspring born to obese mothers had impaired peripheral insulin signaling that was associated with mitochondrial dysfunction and altered mitochondrial dynamic and complex proteins in skeletal muscle. This mitochondrial phenotype persisted through the female germline and was passed down to the second and third generations. Our results indicate that maternal programming of metabolic disease can be passed through the female germline and that the transfer of aberrant oocyte mitochondria to subsequent generations may contribute to the increased risk for developing insulin resistance.
Department of Obstetrics and Gynecology, Washington University School of Medicine, 425 South Euclid Avenue, St. Louis, MO 63110, USA.
Jessica L
JL
Saben
Department of Obstetrics and Gynecology, Washington University School of Medicine, 425 South Euclid Avenue, St. Louis, MO 63110, USA.
Anna L
AL
Boudoures
Department of Obstetrics and Gynecology, Washington University School of Medicine, 425 South Euclid Avenue, St. Louis, MO 63110, USA.
Zeenat
Z
Asghar
Department of Obstetrics and Gynecology, Washington University School of Medicine, 425 South Euclid Avenue, St. Louis, MO 63110, USA.
Alysha
A
Thompson
Department of Obstetrics and Gynecology, Washington University School of Medicine, 425 South Euclid Avenue, St. Louis, MO 63110, USA.
Andrea
A
Drury
Department of Obstetrics and Gynecology, Washington University School of Medicine, 425 South Euclid Avenue, St. Louis, MO 63110, USA.
Wendy
W
Zhang
Department of Obstetrics and Gynecology, Washington University School of Medicine, 425 South Euclid Avenue, St. Louis, MO 63110, USA.
Maggie
M
Chi
Department of Obstetrics and Gynecology, Washington University School of Medicine, 425 South Euclid Avenue, St. Louis, MO 63110, USA.
Andrew
A
Cusumano
Department of Obstetrics and Gynecology, Washington University School of Medicine, 425 South Euclid Avenue, St. Louis, MO 63110, USA.
Suzanne
S
Scheaffer
Department of Obstetrics and Gynecology, Washington University School of Medicine, 425 South Euclid Avenue, St. Louis, MO 63110, USA. Electronic address: moleyk@wustl.edu.
Kelle H
KH
Moley
D000818:Animals; D059305:Diet, High-Fat; D004040:Dietary Carbohydrates; D005260:Female; D005854:Germ Cells / Q000378:metabolism*; D018149:Glucose Intolerance / Q000150:complications; D040582:Inheritance Patterns; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D063154:Mitochondrial Dynamics; D018482:Muscle, Skeletal / Q000378:metabolism / Q000648:ultrastructure; D009865:Oocytes / Q000378:metabolism / Q000648:ultrastructure; D011247:Pregnancy; D015398:Signal Transduction
D004040:Dietary Carbohydrates