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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:14

Enthalten in:

Biomolecules - 14(2024), 3 vom: 26. Feb.

Sprache:

Englisch

Beteiligte Personen:

Almeida-Reis, Sandra [VerfasserIn]
Carvalho, Alexandra [VerfasserIn]
Dias, Conceição [VerfasserIn]
Brito, Raquel [VerfasserIn]
Silva, Rita [VerfasserIn]
Almeida-Santos, Teresa [VerfasserIn]
Ramalho-Santos, João [VerfasserIn]
Sousa, Ana Paula [VerfasserIn]

Links:

Volltext

Themen:

8L70Q75FXE
ATP synthase
Adenosine Triphosphate
Cumulus cells
Journal Article
Maternal aging
Mitochondria
Oxidative phosphorylation
Reactive Oxygen Species

Anmerkungen:

Date Completed 29.03.2024

Date Revised 30.03.2024

published: Electronic

Citation Status MEDLINE

doi:

10.3390/biom14030281

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM370302486