CD38 regulates ovarian function and fecundity via NAD+ metabolism

Perrone, Rosalba; Ashok Kumaar, Prasanna Vadhana; Haky, Lauren; Hahn, Cosmo; Riley, Rebeccah; Balough, Julia; Zaza, Giuliana; Soygur, Bikem; Hung, Kaitlyn; Prado, Leandro; Kasler, Herbert G.; Tiwari, Ritesh; Matsui, Hiroyuki; Hormazabal, Genesis Vega; Heckenbach, Indra; Scheibye-Knudsen, Morten; Duncan, Francesca E.; Verdin, Eric

doi:10.1016/j.isci.2023.107949

Cited by 13 publications

(13 citation statements)

References 78 publications

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“…CD38 deficiency in mice resulted in an increased number of follicles and enhanced fertility [62]. These findings suggested that CD38 might have played a role in inhibiting follicle development, apoptosis, and follicular atresia.…”

Section: Nad + Consumption By Cd38 and Its Role In Female Reproductionmentioning

confidence: 87%

“…Decreases in NAD + levels are associated with hallmarks of aging. Recent research investigations have demonstrated that age-related conditions, such as cancer, metabolic disorders, Alzheimer's disease, neurodegenerative diseases, and fertility decline, are linked to alterations in NAD + homeostasis [56,61,62]. Many cellular and systemic processes depend on NAD + homeostasis, which balances NAD + synthesis and consumption.…”

Section: Nad + and Its Metabolism 41 Overview Of Nad + And Its Import...mentioning

confidence: 99%

“…CD38 has been detected in various cells and tissues, including immune cells, the liver, testis, kidney, and brain. Recently, its expression in the ovary has also been documented [62]. It is crucial for intracellular calcium signaling and generates the second messengers adenosine diphosphoribose (ADPR) (NAD + -glycohydrolase activity) and cyclic ADPR (cADPR) (cyclase activity) [151,152].…”

Section: Nad + Consumption By Cd38 and Its Role In Female Reproductionmentioning

confidence: 99%

“…Oocytes of higher quality were more likely to have been fertilized and developed into healthy embryos. Studies demonstrated that CD38 deficiency in mice led to improved oocyte quality [62]. CD38 has been shown to play a crucial role in regulating important metabolic processes, including glucose tolerance and insulin sensitivity, which could have significantly influenced the reproductive system [148,155,156].…”

Section: Nad + Consumption By Cd38 and Its Role In Female Reproductionmentioning

confidence: 99%

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A Molecular Perspective and Role of NAD+ in Ovarian Aging

Ahmed,

Riaz,

et al. 2024

IJMS

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The decline in female fecundity is linked to advancing chronological age. The ovarian reserve diminishes in quantity and quality as women age, impacting reproductive efficiency and the aging process in the rest of the body. NAD+ is an essential coenzyme in cellular energy production, metabolism, cell signaling, and survival. It is involved in aging and is linked to various age-related conditions. Hallmarks associated with aging, diseases, and metabolic dysfunctions can significantly affect fertility by disturbing the delicate relationship between energy metabolism and female reproduction. Enzymes such as sirtuins, PARPs, and CD38 play essential roles in NAD+ biology, which actively consume NAD+ in their enzymatic activities. In recent years, NAD+ has gained much attention for its role in aging and age-related diseases like cancer, Alzheimer’s, cardiovascular diseases, and neurodegenerative disorders, highlighting its involvement in various pathophysiological processes. However, its impact on female reproduction is not well understood. This review aims to bridge this knowledge gap by comprehensively exploring the complex interplay between NAD+ biology and female reproductive aging and providing valuable information that could help develop plans to improve women’s reproductive health and prevent fertility issues.

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Section: Nad + Consumption By Cd38 and Its Role In Female Reproductionmentioning

confidence: 87%

Section: Nad + and Its Metabolism 41 Overview Of Nad + And Its Import...mentioning

confidence: 99%

Section: Nad + Consumption By Cd38 and Its Role In Female Reproductionmentioning

confidence: 99%

Section: Nad + Consumption By Cd38 and Its Role In Female Reproductionmentioning

confidence: 99%

See 2 more Smart Citations

A Molecular Perspective and Role of NAD+ in Ovarian Aging

Ahmed,

Riaz,

et al. 2024

IJMS

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“…CD38 deficiency enhances ovarian reserves and reproductive capacity in young female animals, and it can alleviate ovarian inflammation in aging animals by reducing multinucleated macrophage giant cells postreproduction. These beneficial changes are associated with increased ovarian NAD + levels [ 248 ] (Fig. 3 ).…”

Section: Regulatory Mechanism Of Nad + Metabolism In Ovarian Agingmentioning

confidence: 99%

Impact of NAD+ metabolism on ovarian aging

Liang,

Huang,

Song

et al. 2023

Immun Ageing

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Nicotinamide adenine dinucleotide (NAD+), a crucial coenzyme in cellular redox reactions, is closely associated with age-related functional degeneration and metabolic diseases. NAD exerts direct and indirect influences on many crucial cellular functions, including metabolic pathways, DNA repair, chromatin remodeling, cellular senescence, and immune cell functionality. These cellular processes and functions are essential for maintaining tissue and metabolic homeostasis, as well as healthy aging. Causality has been elucidated between a decline in NAD levels and multiple age-related diseases, which has been confirmed by various strategies aimed at increasing NAD levels in the preclinical setting. Ovarian aging is recognized as a natural process characterized by a decline in follicle number and function, resulting in decreased estrogen production and menopause. In this regard, it is necessary to address the many factors involved in this complicated procedure, which could improve fertility in women of advanced maternal age. Concerning the decrease in NAD+ levels as ovarian aging progresses, promising and exciting results are presented for strategies using NAD+ precursors to promote NAD+ biosynthesis, which could substantially improve oocyte quality and alleviate ovarian aging. Hence, to acquire further insights into NAD+ metabolism and biology, this review aims to probe the factors affecting ovarian aging, the characteristics of NAD+ precursors, and the current research status of NAD+ supplementation in ovarian aging. Specifically, by gaining a comprehensive understanding of these aspects, we are optimistic about the prominent progress that will be made in both research and therapy related to ovarian aging.

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The therapeutic perspective of NAD+ precursors in age-related diseases

Iqbal,

Nakagawa

2024

Biochemical and Biophysical Research Communications

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CD38 regulates ovarian function and fecundity via NAD+ metabolism

Cited by 13 publications

References 78 publications

A Molecular Perspective and Role of NAD+ in Ovarian Aging

A Molecular Perspective and Role of NAD+ in Ovarian Aging

Impact of NAD+ metabolism on ovarian aging

The therapeutic perspective of NAD+ precursors in age-related diseases

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