Obese mice have decreased uterine contractility and altered energy metabolism in the uterus at term gestation

• Published in: Biology of reproduction 2024-09, Vol.111 (3), p.678-693
• Main Authors: Prifti, Kevin K., McCarthy, Ronald, Ma, Xiaofeng, Finck, Brian N., England, Sarah K., Frolova, Antonina I.
• Format: Article
• Language: English
• Subjects: Animals; contractility; Diet; Dystocia - metabolism; Dystocia - physiopathology; Energy metabolism; Energy Metabolism - physiology; Energy resources; Energy utilization; Fatty acids; Female; metabolism; Metabolomics; Mice; Mice, Inbred C57BL; Mice, Obese; Muscle contraction; Myometrium; Myometrium - metabolism; Obesity; Obesity - metabolism; Obesity - physiopathology; Parturition; Pregnancy; RESEARCH ARTICLE; Smooth muscle; Transcriptomics; Uterine Contraction - physiology; Uterus; Uterus - metabolism
• ISSN: 0006-3363; 1529-7268; 1529-7268
• DOI: 10.1093/biolre/ioae086

Over 35% of reproductive-age women in the USA have obesity, putting them at increased risk for numerous obstetric complications due to abnormal labor. While the association between maternal obesity and abnormal labor has been well documented, the mechanisms responsible for this remain understudied. The uterine smooth muscle, myometrium, has high energy needs in order to fuel regular uterine contractions during parturition. However, the precise mechanisms by which the myometrium meets its energy demands has not been defined. Here, our objective was to define the effects of obesity on energy utilization in the myometrium during labor. We generated a mouse model of maternal diet-induced obesity and found that these mice had a higher rate of dystocia than control chow-fed mice. Moreover, compared to control chow-fed mice, DIO mice at term, both before and during labor had lower in vivo spontaneous uterine contractility. Untargeted transcriptomic and metabolomic analyses suggest that diet-induced obesity is associated with elevated long-chain fatty acid uptake and utilization in the uterus, but also an accumulation of medium-chain fatty acids. Diet-induced obesity uteri also had an increase in the abundance of long chain-specific beta-oxidation enzymes, which may be responsible for the observed increase in long-chain fatty acid utilization. This altered energy substrate utilization may be a contributor to the observed contractile dysfunction. Summary Sentence Mice with diet-induced obesity have altered uterine energy metabolism and decreased contractility resulting in labor dystocia. Graphical Abstract