Cumulus cells mitochondrial dysfunction in advanced-age women

Vazquez‐Levin, Mónica H.

doi:10.1016/j.fertnstert.2022.06.024

Cited by 1 publication

(1 citation statement)

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“…Liu et al described an impairment in mitochondrial functions of granulosa cells (GCs) in aged women (aged ≥ 37), related to an OXPHOS dysfunction [ 9 ]. Lu and collaborators performed a transcriptomic study of hCCs and found a set of differentially expressed genes, specifically related to OXPHOS, that were downregulated in the AMA group [ 41 , 42 ]. Another study, which investigated the metabolic changes in GCs in patients grouped according to the Poseidon classification, observed that age was the main contributor to OXPHOS dysfunction [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Dysfunction in Advanced Maternal Aged Cumulus Cells: A Possible Link to ATP Synthase Impairment?

Almeida-Reis,

Carvalho,

Dias

et al. 2024

Biomolecules

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Age-related changes in the mitochondrial status of human cumulus cells (hCCs) impact oocyte quality; however, the relationship between hCC mitochondrial (dys)function and reproductive aging remains poorly understood. This study aimed to establish the interplay between hCC mitochondrial dysfunction and women’s reproductive potential. In this investigation, 266 women were enrolled and categorized into two groups based on their age: a young group (<35 years old) and an advanced maternal age (AMA) group (≥35 years old). Comprehensive analysis of reproductive outcomes was conducted in our population. Various mitochondrial-related parameters were analyzed across distinct subsets. Specifically, mitochondrial membrane potential (∆Ψm) and mitochondrial mass were examined in 53 samples, mtDNA content in 25 samples, protein levels in 23 samples, bioenergetic profiles using an XF24 Extracellular Flux Analyzer in 6 samples, and levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) in 39 and 43 samples, respectively. In our study, the reproductive potential of AMA women sharply decreased, as expected. Additionally, an impairment in the mitochondrial function of hCCs in older women was observed; however, no differences were found in terms of mitochondrial content. Regarding oxidative phosphorylation, metabolic profiling of hCCs from AMA women indicated a decrease in respiratory capacity, which was correlated with an age-dependent decrease in the ATP synthase (ATP5A1) protein level. However, intracellular ROS and ATP levels did not differ between groups. In conclusion, our study indicates that age-related dysfunction in hCCs is associated with impaired mitochondrial function, and, although further studies are required, ATP synthase could be relevant in this impairment.

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