Mitochondria in Human Fertility and Infertility

Mendoza-Tesarik, Raquel

doi:10.3390/ijms24108950

Cited by 11 publications

(4 citation statements)

References 32 publications

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“…It was reported that necrosis fosters mitochondrial dysfunction due to inner membrane depolarization, mitochondrial swelling, and rupture, resulting in the loss of ATP production [36]. Mitochondrial damage that occurs in oocytes during their long life span is recognized as one of the most important factors that adversely affect fertility in humans [37]. Furthermore, a significant increase in the diameter of overactivated eggs (Figures 1, 2, 4 and 7) indicates that membrane permeability is augmented and cellular osmotic homeostasis is lost in these eggs.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous Overactivation of Xenopus Frog Eggs Triggers Necrotic Cell Death

Tokmakov,

Teranishi,

Sato

2024

IJMS

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The excessive activation of frog eggs, referred to as overactivation, can be initiated by strong oxidative stress, leading to expedited calcium-dependent non-apoptotic cell death. Overactivation also occurs spontaneously, albeit at a low frequency, in natural populations of spawned frog eggs. Currently, the cytological and biochemical events of the spontaneous process have not been characterized. In the present study, we demonstrate that the spontaneous overactivation of Xenopus frog eggs, similarly to oxidative stress- and mechanical stress-induced overactivation, is characterized by the fast and irreversible contraction of the egg’s cortical layer, an increase in egg size, the depletion of intracellular ATP, a drastic increase in the intracellular ADP/ATP ratio, and the degradation of M phase-specific cyclin B2. These events manifest in eggs in the absence of caspase activation within one hour of triggering overactivation. Importantly, substantial amounts of ATP and ADP leak from the overactivated eggs, indicating that plasma membrane integrity is compromised in these cells. The rupture of the plasma membrane and acute depletion of intracellular ATP explicitly define necrotic cell death. Finally, we report that egg overactivation can occur in the frog’s genital tract. Our data suggest that mechanical stress may be a key factor promoting egg overactivation during oviposition in frogs.

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Section: Discussionmentioning

confidence: 99%

Spontaneous Overactivation of Xenopus Frog Eggs Triggers Necrotic Cell Death

Tokmakov,

Teranishi,

Sato

2024

IJMS

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“…Mitochondrial impairment has been pointed out as an aging hallmark [ 3 , 17 , 21 , 31 , 36 ], and its involvement in oocyte deterioration in AMA women has already been described [ 37 , 38 ]. Abnormalities in mitochondrial ultrastructure, dynamics and integrity, metabolism, and mtDNA mutations and deletions [ 17 ] have been studied in follicular cells.…”

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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“…Mitochondria play a pivotal role in cellular energy production through oxidative phosphorylation, serving as vital regulators of energy metabolism, metabolic homeostasis, and oxidative stress management, thus exerting significant influence over reproductive aging processes. Within germ cells, mitochondria fulfill indispensable roles in supporting energy-intensive processes such as oocyte maturation, fertilization, and subsequent embryonic development [ 9 , 10 , 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Intravascular Laser Blood Irradiation (ILIB) Enhances Antioxidant Activity and Energy Metabolism in Aging Ovaries

Lin,

Li,

Chern

et al. 2024

JPM

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Background: Ovarian aging is characterized by the accumulation of free radicals, leading to tissue damage and affecting reproductive health. Intravascular laser irradiation of blood (ILIB, using a low-energy He-Ne laser) is known for its efficacy in treating vascular-related diseases by reducing free radicals and inflammation. However, its impact on ovarian aging remains unexplored. This study aimed to investigate the effects of ILIB on oxidative stress and energy metabolism in aging ovaries. Methods: Genetic analysis was conducted on 75 infertile patients with aging ovaries, divided into ILIB-treated and control (CTRL) groups. Patients underwent two courses of laser treatment, and clinical parameters were evaluated. Cumulus cells were collected for the genetic analysis of oxeiptosis, glycolysis, and the tricarboxylic acid (TCA) cycle. Results: The analysis of gene expression patterns revealed intriguing findings in ILIB-treated patients compared to the untreated group. Notably, ILIB treatment resulted in significant upregulation of oxeiptosis-related genes AIFM1 and NRF2, suggesting a potential protective effect against oxidative stress-induced cell death. Furthermore, ILIB treatment led to a downregulation of glycolysis-associated gene hexokinase 2 (HK2), indicating a shift away from anaerobic metabolism, along with an increase in PDHA levels, indicative of enhanced mitochondrial function. Consistent with these changes, ILIB-treated patients exhibited elevated expression of the key TCA cycle genes citrate synthase (CS), succinate dehydrogenase complex subunit A (SDHA), and fumarate hydratase (FH), signifying improved energy metabolism. Conclusion: The findings from this study underscore the potential of ILIB as a therapeutic strategy for mitigating ovarian aging. By targeting oxidative stress and enhancing energy metabolism, ILIB holds promise for preserving ovarian function and reproductive health in aging individuals. Further research is warranted to elucidate the underlying mechanisms and optimize the application of ILIB in clinical settings, with the ultimate goal of improving fertility outcomes in women experiencing age-related ovarian decline.

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Mitochondria in Human Fertility and Infertility

Cited by 11 publications

References 32 publications

Spontaneous Overactivation of Xenopus Frog Eggs Triggers Necrotic Cell Death

Spontaneous Overactivation of Xenopus Frog Eggs Triggers Necrotic Cell Death

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

Intravascular Laser Blood Irradiation (ILIB) Enhances Antioxidant Activity and Energy Metabolism in Aging Ovaries

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