Cellular Stress Responses in Oocytes: Molecular Changes and Clinical Implications

Marei, Waleed F.A.; Leroy, Jo

doi:10.1007/5584_2021_690

Cited by 10 publications

(8 citation statements)

References 108 publications

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“…Various factors may contribute to cellular and oxidative stress during embryo culture including oxygen tension 50 , glucose concentration 12 , light, temperature, culture media supplements and culture equipment 51 . Increased stress levels during embryo culture can lead to detrimental effects such as increased genomic instability 52 and endoplasmic reticulum (ER) stress 12 , 52 , which can activate the unfolded protein response (UPR) and trigger cell death 53 . Therefore, gaining a deeper understanding of cellular responses to conditions that elevate oxidative stress is crucial for developing enhanced culture environments and generating healthy embryos and offspring.…”

Section: Discussionmentioning

confidence: 99%

NRF2 attenuation aggravates detrimental consequences of metabolic stress on cultured porcine parthenote embryos

Glanzner,

da Silva Sousa,

Gutierrez

et al. 2024

Sci Rep

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The nuclear factor erythroid 2–related factor 2 (NRF2) is a crucial transcription factor that plays a central role in regulating oxidative stress pathways by binding antioxidant response elements, but its involvement in early embryo development remains largely unexplored. In this study, we demonstrated that NRF2 mRNA is expressed in porcine embryos from day 2 to day 7 of development, showing a decrease in abundance from day 2 to day 3, followed by an increase on day 5 and day 7. Comparable levels of NRF2 mRNA were observed between early-cleaving and more developmental competent embryos and late-cleaving and less developmental competent embryos on day 4 and day 5 of culture. Attenuation of NRF2 mRNA significantly decreased development of parthenote embryos to the blastocyst stage. When NRF2-attenuated embryos were cultured in presence of 3.5 mM or 7 mM glucose, development to the blastocyst stage was dramatically decreased in comparison to the control group (15.9% vs. 27.8% for 3.5 mM glucose, and 5.4% vs. 25.3% for 7 mM glucose). Supplementation of melatonin moderately improved the development of NRF2-attenuated embryos cultured in presence of 0.6 mM glucose. These findings highlight the importance of NRF2 in early embryo development, particularly in embryos cultured under metabolically stressful conditions.

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Section: Discussionmentioning

confidence: 99%

NRF2 attenuation aggravates detrimental consequences of metabolic stress on cultured porcine parthenote embryos

Glanzner,

da Silva Sousa,

Gutierrez

et al. 2024

Sci Rep

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“…It is important to keep in mind that the increased oocyte mitochondrial ultrastructural abnormalities in response to maternal and/or offspring OB diet does not necessarily mean that other mitochondrial or cellular metabolic functions are affected. Oocytes contain around hundred thousand mitochondria and display several adaptive mechanisms that may be used to compensate for energy deficit or overload ( Runkel et al, 2014 ; Marei and Leroy, 2022 ). Previous studies from our laboratory have shown that the percentage of mitochondria with abnormal morphology in control Swiss oocytes is around 20% ( Smits et al, 2022a ).…”

Section: Discussionmentioning

confidence: 99%

The impact of a maternal and offspring obesogenic diet on daughter’s oocyte mitochondrial ultrastructure and bioenergetic responses. Insights from an outbred mouse model

Xhonneux,

Marei,

Meulders

et al. 2023

Front. Physiol.

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Obesity affects oocyte mitochondrial functions and reduces oocyte quality and fertility. Obesity may also increase the risk of metabolic disorders in the offspring. Children are likely to follow their parents lifestyle and diet, which also contributes to the increased prevelance of obesity across generations. We hypothesise that the impact of obesogenic (OB) diet and obesity on oocyte mitochondrial functions is different in offspring born to obese mothers compared to those born to healthy mothers. To test this hypothesis, we fed a control (C, 10% fat, 7% sugar) or an OB diet (60% fat, 20% sugar) to female mice (for 7 weeks (w)) and then to their female offspring (for 7w after weaning) in a 2 × 2 factorial design (C » C, n = 35, C » OB, n = 35, OB » C n = 49 and OB » OB, n = 50). Unlike many other studies, we used an outbred Swiss mouse model to increase the human pathophysiological relevance. Offspring were sacrificed at 10w and their oocytes were collected. Offspring OB diet increased oocyte lipid droplet content, mitochondrial activity and reactive oxygen species (ROS) levels, altered mitochondrial ultrastructure and reduced oocyte pyruvate consumption. Mitochondrial DNA copy numbers and lactate production remained unaffected. Mitochondrial ultrastructure was the only factor where a significant interaction between maternal and offspring diet effect was detected. The maternal OB background resulted in a small but significant increase in offspring’s oocyte mitochondrial ultrastructural abnormalities without altering mitochondrial inner membrane potential, active mitochondrial distribution, mitochondrial DNA copy numbers, or ROS production. This was associated with reduced mitochondrial complex III and V expression and reduced pyruvate consumption which may be compensatory mechanisms to control mitochondrial inner membrane potential and ROS levels. Therefore, in this Swiss outbred model, while offspring OB diet had the largest functional impact on oocyte mitochondrial features, the mitochondrial changes due to the maternal background appear to be adaptive and compensatory rather than dysfunctional.

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“…The impact of in vitro culture (IVC) techniques on oocyte quality and further development is a very important factor to consider as we may assume that oocytes collected from metabolically compromised individuals are more sensitive to such suboptimal in vitro environments (Marei and Leroy 2021). On the other hand, the in vitro oocyte handling, and further culture may create a unique opportunity to provide a supportive and even "therapeutic" in vitro environment to recover the quality of oocytes collected from patients with a compromised (metabolic) health (Marei et al 2019b).…”

Section: The Growing Importance Of the Oocyte's Culture Environment I...mentioning

confidence: 99%

“…However, embryos derived from metabolically-compromised oocytes have higher rates of fragmentation and developmental arrest during early development, and higher rates of blastomere apoptosis (Marei et al 2019b). This illustrates that the endogenous UPR mechanisms are not sufficient to combat the damage or prevent its further aggravation after fertilization, leading to failure of embryo development, usually before blastocyst formation (Diskin et al 2011;Marei et al 2019b;Marei and Leroy 2021). The increased intracellular levels of ROS and MMP may persist after fertilization, resulting in carry-over effects during early embryo development (Marei et al 2019b).…”

Section: Mitochondria As a Key Target To Improve Oocyte Qualitymentioning

confidence: 99%

“…Controlling mitochondrial ROS production and improving the capacity of mitochondria to resist cellular stress can be an effective approach to improve oocyte and early embryos quality, or at least to reduce stress to tolerable levels until mitochondrial biogenesis is enabled at later stages after blastocyst formation (Lima et al 2018), i.e. for mitochondrial damage to be self-repaired (Marei and Leroy 2021). Conventional antioxidants are usually effective in prevention of ROS accumulation, but have limited capacity to alleviate oxidative stress or restore mitochondrial functions in oocytes when metabolic stress is ongoing (Smits et al 2020a;De Bie et al 2021).…”

Section: Mitochondria As a Key Target To Improve Oocyte Qualitymentioning

confidence: 99%

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Maternal metabolic health and fertility: we should not only care about but also for the oocyte!

Leroy

Meulders

Moorkens

et al. 2022

Reprod. Fertil. Dev.

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Reduced oocyte quality, mainly due to mitochondrial dysfunction, is a key cause of subfertility in patients with metabolic diseases such as obesity. Recent fundamental understanding of the underlying mechanisms highlights the importance of developing effective preconception care strategies not only to improve metabolic health, but also oocyte quality. Minimizing mitochondrial oxidative stress either in vivo or in vitro is a promising solution, however further investigations should consider the long-term consequences on epigenetic programming and offspring health.

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Cellular Stress Responses in Oocytes: Molecular Changes and Clinical Implications

Cited by 10 publications

References 108 publications

NRF2 attenuation aggravates detrimental consequences of metabolic stress on cultured porcine parthenote embryos

NRF2 attenuation aggravates detrimental consequences of metabolic stress on cultured porcine parthenote embryos

The impact of a maternal and offspring obesogenic diet on daughter’s oocyte mitochondrial ultrastructure and bioenergetic responses. Insights from an outbred mouse model

Maternal metabolic health and fertility: we should not only care about but also for the oocyte!

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