Activated PI3K/AKT Signaling Pathway Associates with Oxidative Stress and Impaired Developmental Potential of Vitrified-Thawed Oocytes

Li, Jun; Yang, Xuemei; Liu, Fang; Song, Yaman; Liu, Yuanke

doi:10.1007/s43032-019-00036-1

Cited by 7 publications

(3 citation statements)

References 39 publications

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“…Among laboratory manipulation of gametes, cryopreservation is a condition known to exacerbate post-ovulatory aging [118,119]. As expected, vitrified-thawed mouse oocytes showed a reduction of Sirt3, along with OS markers and mito-damage [120].…”

Section: Sirtuins Mitochondria and Female Reproductionsupporting

confidence: 59%

Mitochondrial Sirtuins in Reproduction

et al. 2021

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Mitochondria act as hubs of numerous metabolic pathways. Mitochondrial dysfunctions contribute to altering the redox balance and predispose to aging and metabolic alterations. The sirtuin family is composed of seven members and three of them, SIRT3-5, are housed in mitochondria. They catalyze NAD+-dependent deacylation and the ADP-ribosylation of mitochondrial proteins, thereby modulating gene expression and activities of enzymes involved in oxidative metabolism and stress responses. In this context, mitochondrial sirtuins (mtSIRTs) act in synergistic or antagonistic manners to protect from aging and aging-related metabolic abnormalities. In this review, we focus on the role of mtSIRTs in the biological competence of reproductive cells, organs, and embryos. Most studies are focused on SIRT3 in female reproduction, providing evidence that SIRT3 improves the competence of oocytes in humans and animal models. Moreover, SIRT3 protects oocytes, early embryos, and ovaries against stress conditions. The relationship between derangement of SIRT3 signaling and the imbalance of ROS and antioxidant defenses in testes has also been demonstrated. Very little is known about SIRT4 and SIRT5 functions in the reproductive system. The final goal of this work is to understand whether sirtuin-based signaling may be taken into account as potential targets for therapeutic applications in female and male infertility.

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Section: Sirtuins Mitochondria and Female Reproductionsupporting

confidence: 59%

Mitochondrial Sirtuins in Reproduction

et al. 2021

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“…Mitochondria are a major source of oxidative stress because the majority of superoxide reactive oxygen species are generated from the mitochondrial respiratory chain (R. Zhang, 2015). In vitrified oocytes, the redox homeostasis is destroyed and the mitochondria are also impaired, leading to an increased ROS level and a decrease of mitochondrial membrane potential (Li et al, 2020). Oxidative stress‐induced mitochondrial dysfunction in oocytes is associated with aneuploidy, fertilization failure, and reduced embryonic viability (Reynier et al, 2001; Schon et al, 2000; Van Blerkom, 2011).…”

Section: Introductionmentioning

confidence: 99%

Nampt affects mitochondrial function in aged oocytes by mediating the downstream effector FoxO3a

Zhuan

et al. 2021

Journal Cellular Physiology

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Maternal aging can impair the quality and decrease the developmental competence of ovulated oocytes. In this study, compromised germinal vesicle breakdown (GVBD) was found in aged mice oocytes. Furthermore, we observed increased reactive oxygen species (ROS) and mitochondrial Ca2+ levels, along with reduced mitochondrial temperature in aged oocytes. Maternal aging also changed the crotonylation level in oocytes. Forkhead box O3 (FoxO3a), a member of the forkhead protein family involved in the regulation of cell survival and life span reached a peak level in the metaphase II stage. Compared with a younger group, FoxO3a expression increased in aged oocytes. Intracellular localization of FoxO3a changed from the cytoplasm to chromatin in response to aging. The expression of the upstream regulator nicotinamide‐phosphoribosyltransferase (Nampt) peaked in the GVBD stage. Moreover, Nampt expression was increased in aged oocytes, and more intense staining of Nampt was found in aged mice ovary. To further study the role of Nampt in mitochondrial function, specific agonist P7C3 and inhibitor FK866 were applied to aged oocytes, and FK866 significantly decreased adenosine triphosphate and mitochondrial membrane potential. In conclusion, mitochondrial dysfunction in aged oocytes was associated with elevated FoxO3a, and suppression of Nampt could further impair mitochondrial function.

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“…the PI3K/AKT pathway is an important signal that regulates apoptosis by modulating oxidative stress. It was found that this pathway was involved in the response to oxidative stress during vitrification/warming process and the developmental potential of the warming mouse oocytes ( 44 ).…”

Section: Discussionmentioning

confidence: 99%

Melatonin improves the vitrification of sheep morulae by modulating transcriptome

Ji,

Liu,

Yan

et al. 2023

Front. Vet. Sci.

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Embryo vitrification technology is widely used in livestock production, but freezing injury has been a key factor hindering the efficiency of embryo production. There is an urgent need to further analyze the molecular mechanism of embryo damage by the vitrification process. In the study, morulae were collected from Hu sheep uterine horns after superovulation and sperm transfusion. Morulae were Cryotop vitrified and warmed. Nine morulae were in the vitrified control group (frozen), and seven morulae were vitrified and warmed with 10−5 M melatonin (melatonin). Eleven non-frozen morulae were used as controls (fresh). After warming, each embryo was sequenced separately for library construction and gene expression analysis. p < 0.05 was used to differentiate differentially expressed genes (DEG). The results showed that differentiated differentially expressed genes (DEG) in vitrified morulae were mainly enriched in protein kinase activity, adhesion processes, calcium signaling pathways and Wnt, PI3K/AKT, Ras, ErbB, and MAPK signaling pathways compared to controls. Importantly, melatonin treatment upregulated the expression of key pathways that increase the resistance of morulae against vitrification induced damage. These pathways include kinase activity pathway, ErbB, and PI3K/Akt signaling pathway. It is worth mentioning that melatonin upregulates the expression of XPA, which is a key transcription factor for DNA repair. In conclusion, vitrification affected the transcriptome of in vivo-derived Hu sheep morulae, and melatonin had a protective effect on the vitrification process. For the first time, the transcriptome profiles caused by vitrification and melatonin in sheep morulae were analyzed in single embryo level. These data obtained from the single embryo level provide an important molecular mechanism for further optimizing the cryopreservation of embryos or other cells.

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Activated PI3K/AKT Signaling Pathway Associates with Oxidative Stress and Impaired Developmental Potential of Vitrified-Thawed Oocytes

Cited by 7 publications

References 39 publications

Mitochondrial Sirtuins in Reproduction

Mitochondrial Sirtuins in Reproduction

Nampt affects mitochondrial function in aged oocytes by mediating the downstream effector FoxO3a

Melatonin improves the vitrification of sheep morulae by modulating transcriptome

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