Sirt3 deficiency accelerates ovarian senescence without affecting spermatogenesis in aging mice

Zhu, Jing; Yang, Qingling; Li, Hui; Wang, Yujiao; Jiang, Yuqing; Wang, Huan; Cong, Luping; Xu, Jimmy P.; Shen, Zhaoyang; Chen, Wenhui; Zeng, Xinxin; Wang, Mengchen; Lei, M.; Sun, Yingpu

doi:10.1016/j.freeradbiomed.2022.10.324

Cited by 19 publications

(11 citation statements)

References 65 publications

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“…2 E). Given that mice are polytocous mammals [ 44 ], the evaluation of estrous cycles and litter sizes yielded no substantial differences between the wild-type and knockout mice. These findings collectively suggest that the Sestrin protein family may not assume a critical role in influencing female fertility in mice.…”

Section: Resultsmentioning

confidence: 99%

Sestrin1, 2, and 3 are dispensable for female fertility in mice

Wang,

Chen,

Zeng

et al. 2024

J Ovarian Res

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Background Sestrins have been implicated in regulating aging in various organs through multiple pathways. However, their roles in ovarian aging remain unrevealed. Methods Female Sestrin1−/−, Sestrin2−/−, and Sestrin3−/− mice were generated using the CRISPR-Cas9 system. Body weights, little sizes, ovarian weights, estrous cyclicity, and follicle number in female mice were observed. ELISA was utilized to measure serum anti-Müllerian hormone (AMH) levels. Real time PCR, western blot, immunofluorescence, and Masson trichrome staining were employed for assessment of aging-related change. Results The deletion of Sestrin 1, 2, or 3 had no discernible impact on body weights,or serum AMH levels in female mice at the age of 12 months. And there were no discernible differences in litter sizes or estrous cyclicity which were assessed at the age of 8 months. At the age of 12 months, no significant differences were observed in ovarian weights or follicle numbers among the knockout mice. Consistently, the extent of fibrosis within the ovaries remained comparable across all experimental groups at this age. Additionally, autophagy, apoptosis, DNA damage, and inflammation within the ovaries were also found to be comparable to those in wild-type mice of the same age. Conclusions The loss of Sestrin 1, 2, or 3 does not exert a noticeable influence on ovarian function during the aging process. Sestrin1, 2, and 3 are not essential for female fertility in mice.

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Section: Resultsmentioning

confidence: 99%

Sestrin1, 2, and 3 are dispensable for female fertility in mice

Wang,

Chen,

Zeng

et al. 2024

J Ovarian Res

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“…SIRT3 is a mitochondrial sirtuin and its ovarian expression decreases with age leading to mitochondrial dysfunction and deleterious spindle assembly 64 . Overexpression of SIRT2 improves fertility and recapitulates the benefits of NMN supplementation 10 .…”

Section: Discussionmentioning

confidence: 99%

CD38 regulates ovarian function and fecundity via NAD⁺metabolism

Perrone,

Ashok Kumaar,

Haky

et al. 2023

Preprint

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SummaryMammalian female reproductive lifespan is typically significantly shorter than life expectancy and is associated with a decrease in ovarian NAD+ levels. However, the mechanisms underlying this loss of ovarian NAD+ are unclear. Here, we show that CD38, a NAD+ consuming enzyme, is expressed in the ovarian extrafollicular space, primarily in immune cells, and its levels increase with reproductive age. Reproductively young mice lacking CD38 exhibit larger primordial follicle pools, elevated ovarian NAD+ levels, and increased fecundity relative to wild type controls. This larger ovarian reserve results from a prolonged window of follicle formation during early development. However, the beneficial effect of CD38 loss on reproductive function is not maintained at advanced age. Our results demonstrate a novel role of CD38 in regulating ovarian NAD+ metabolism and establishing the ovarian reserve, a critical process that dictates a female’s reproductive lifespan.

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“…NRF1, SIRT1, and SIRT3 are all downregulated in the ovaries of reproductive aging ( 55 – 57 ). In the ovaries of SIRT3 gene knockout mice, there was a decrease in mitochondrial membrane potential, uneven distribution of mitochondria, and a decrease in mtDNA copy number ( 56 ). Ginsenoside Rg1 improves ovarian function by activating SIRT1 and coenzyme Q10 improves ovarian function by increasing the expression of SIRT1 in PGC1α in animal experiments ( 103 , 104 ).…”

Section: Mitochondrial Dysfunction Leads To Ovarian Agingmentioning

confidence: 99%

Mechanisms of mitochondrial dysfunction in ovarian aging and potential interventions

Ju,

Zhao,

et al. 2024

Front. Endocrinol.

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Mitochondria plays an essential role in regulating cellular metabolic homeostasis, proliferation/differentiation, and cell death. Mitochondrial dysfunction is implicated in many age-related pathologies. Evidence supports that the dysfunction of mitochondria and the decline of mitochondrial DNA copy number negatively affect ovarian aging. However, the mechanism of ovarian aging is still unclear. Treatment methods, including antioxidant applications, mitochondrial transplantation, emerging biomaterials, and advanced technologies, are being used to improve mitochondrial function and restore oocyte quality. This article reviews key evidence and research updates on mitochondrial damage in the pathogenesis of ovarian aging, emphasizing that mitochondrial damage may accelerate and lead to cellular senescence and ovarian aging, as well as exploring potential methods for using mitochondrial mechanisms to slow down aging and improve oocyte quality.

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Sirt3 deficiency accelerates ovarian senescence without affecting spermatogenesis in aging mice

Cited by 19 publications

References 65 publications

Sestrin1, 2, and 3 are dispensable for female fertility in mice

Sestrin1, 2, and 3 are dispensable for female fertility in mice

CD38 regulates ovarian function and fecundity via NAD⁺metabolism

Mechanisms of mitochondrial dysfunction in ovarian aging and potential interventions

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Sirt3 deficiency accelerates ovarian senescence without affecting spermatogenesis in aging mice

Cited by 19 publications

References 65 publications

Sestrin1, 2, and 3 are dispensable for female fertility in mice

Sestrin1, 2, and 3 are dispensable for female fertility in mice

CD38 regulates ovarian function and fecundity via NAD+metabolism

Mechanisms of mitochondrial dysfunction in ovarian aging and potential interventions

Contact Info

Product

Resources

About

CD38 regulates ovarian function and fecundity via NAD⁺metabolism