Mitochondrial dysfunction in the offspring of obese mothers and it's transmission through damaged oocyte mitochondria: Integration of mechanisms

Elías-López, A.L.; Vazquez-Mena, Oscar; Sferruzzi‐Perri, Amanda N.

doi:10.1016/j.bbadis.2023.166802

Cited by 8 publications

(3 citation statements)

References 217 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More specifically, the percentages of degenerated mitochondria and mitochondria with increased electron density were increased. Some would explain this by the transfer of aberrant mitochondria from the mother to the offspring due to an inability of the oocyte to activate mitophagy [8,26,39,40]. However, it might also be that altered metabolic and epigenetic programming in the offspring may result in MT adaptations and persistent metabolic alterations that will eventually lead to de novo MT dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Preconception Diet Interventions in Obese Outbred Mice and the Impact on Female Offspring Metabolic Health and Oocyte Quality

Meulders,

Marei,

Xhonneux

et al. 2024

IJMS

View full text Add to dashboard Cite

Obese individuals often suffer from metabolic health disorders and reduced oocyte quality. Preconception diet interventions in obese outbred mice restore metabolic health and oocyte quality and mitochondrial ultrastructure. Also, studies in inbred mice have shown that maternal obesity induces metabolic alterations and reduces oocyte quality in offspring (F1). Until now, the effect of maternal high-fat diet on F1 metabolic health and oocyte quality and the potential beneficial effects of preconception dietary interventions have not been studied together in outbred mice. Therefore, we fed female mice a high-fat/high-sugar (HF/HS) diet for 7 weeks and switched them to a control (CONT) or caloric-restriction (CR) diet or maintained them on the HF/HS diet for 4 weeks before mating, resulting in three treatment groups: diet normalization (DN), CR, and HF/HS. In the fourth group, mice were fed CONT diet for 11 weeks (CONT). HF/HS mice were fed an HF/HS diet from conception until weaning, while all other groups were then fed a CONT diet. After weaning, offspring were kept on chow diet and sacrificed at 11 weeks. We observed significantly elevated serum insulin concentrations in female HF/HS offspring and a slightly increased percentage of mitochondrial ultrastructural abnormalities, mitochondrial size, and mitochondrial mean gray intensity in HF/HS F1 oocytes. Also, global DNA methylation was increased and cellular stress-related proteins were downregulated in HF/HS F1 oocytes. Mostly, these alterations were prevented in the DN group, while, in CR, this was only the case for a few parameters. In conclusion, this research has demonstrated for the first time that a maternal high-fat diet in outbred mice has a moderate impact on female F1 metabolic health and oocyte quality and that preconception DN is a better strategy to alleviate this compared to CR.

show abstract

Section: Discussionmentioning

confidence: 99%

Preconception Diet Interventions in Obese Outbred Mice and the Impact on Female Offspring Metabolic Health and Oocyte Quality

Meulders,

Marei,

Xhonneux

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…Following fertilization, sperm mitochondria are degraded and, thus, mitochondria are inherited solely through the maternal lineage, meaning all mitochondria (and mtDNA) in offspring are derived from those in the mature oocyte. Importantly, however, the mitochondria of oocytes and embryos are sensitive to physiological cues and are highly susceptible to endogenous and external stressors, and mitochondrial signals are emerging as important epigenetic mechanisms by which offspring phenotypes are inherited [ 6 , 7 , 8 ]. Thus, oocyte mitochondria quality and quantity are of utmost importance to embryonic development and postnatal health.…”

Section: Introductionmentioning

confidence: 99%

Dynamics of Mitochondrial DNA Copy Number and Membrane Potential in Mouse Pre-Implantation Embryos: Responses to Diverse Types of Oxidative Stress

Winstanley,

Liu,

Adhikari

et al. 2024

Genes

View full text Add to dashboard Cite

Mitochondria undergo a myriad of changes during pre-implantation embryo development, including shifts in activity levels and mitochondrial DNA (mtDNA) replication. However, how these distinct aspects of mitochondrial function are linked and their responsiveness to diverse stressors is not well understood. Here, we show that mtDNA content increased between 8-cell embryos and the blastocyst stage, with similar copy numbers per cell in the inner cell mass (ICM) and trophectoderm (TE). In contrast, mitochondrial membrane potential (MMP) was higher in TE than ICM. Culture in ambient oxygen (20% O2) altered both aspects of mitochondrial function: the mtDNA copy number was upregulated in ICM, while MMP was diminished in TE. Embryos cultured in 20% O2 also exhibited delayed development kinetics, impaired implantation, and reduced mtDNA levels in E18 fetal liver. A model of oocyte mitochondrial stress using rotenone showed only a modest effect on on-time development and did not alter the mtDNA copy number in ICM; however, following embryo transfer, mtDNA was higher in the fetal heart. Lastly, endogenous mitochondrial dysfunction, induced by maternal age and obesity, altered the blastocyst mtDNA copy number, but not within the ICM. These results demonstrate that mitochondrial activity and mtDNA content exhibit cell-specific changes and are differentially responsive to diverse types of oxidative stress during pre-implantation embryogenesis.

show abstract

“…A leading proposed mechanism is through epigenetic modulation of the genome, which then predisposes affected offspring to exacerbated responses to obesogenic conditions such as diet. A recent study suggested that transmission of disease risk might be mediated through transfer of maternal oocyte-derived dysfunctional mitochondria from mothers with obesity [ 11 ]. Additional mechanisms imparting obesogenic “memory” may be evoked through “trained immunity.”…”

mentioning

confidence: 99%

Obesity research: Moving from bench to bedside to population

Schmidt

2023

PLoS Biol

View full text Add to dashboard Cite

show abstract

Mitochondrial dysfunction in the offspring of obese mothers and it's transmission through damaged oocyte mitochondria: Integration of mechanisms

Cited by 8 publications

References 217 publications

Preconception Diet Interventions in Obese Outbred Mice and the Impact on Female Offspring Metabolic Health and Oocyte Quality

Preconception Diet Interventions in Obese Outbred Mice and the Impact on Female Offspring Metabolic Health and Oocyte Quality

Dynamics of Mitochondrial DNA Copy Number and Membrane Potential in Mouse Pre-Implantation Embryos: Responses to Diverse Types of Oxidative Stress

Obesity research: Moving from bench to bedside to population

Contact Info

Product

Resources

About