NMN can improve oocyte quality and delay reproductive aging

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Recently, with the prominence of problems such as the delay of childbearing age, environmental pollution, and the younger generation of malignant diseases, women's reproductive health is facing severe challenges, and there is a significant downward trend in fertility worldwide.

 

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NMN reverses maternal aging oocyte quality decline

 

In August 2020, a team of Chinese scientists published a new research result in the top biological journal "Cell Reports": supplementation of NAD+ precursor nicotinamide mononucleotide (NMN) effectively improved the quality of maternal aging oocytes, Protecting oocytes from late maternal age-related degeneration can help improve reproductive outcomes and assisted reproductive technologies in older women.

 

High-quality oocytes are a prerequisite for successful fertilization and subsequent embryonic development, the material basis for the beginning of life. In most mammals, female reproductive senescence is particularly manifested by a marked decrease in the number and quality of follicles and oocytes.

 

Studies have shown that female fertility begins to decline in the early 30s and declines more rapidly after the age of 35, with a dramatic increase in the incidence of infertility, miscarriage, embryonic lethality, and birth defects; therefore, low-quality oocytes are critical for It is a common and insurmountable problem for advanced mothers.

 

NMN supplementation not only increased the number of ovulated oocytes in aged mice, but also enhanced their meiotic capacity and fertilization capacity, and NMN could help restore mitochondrial function and inhibit ROS-induced apoptosis of aged oocytes.

 

1.       NMN supplementation improves the quality of aged oocytes by increasing NAD+ content

 

The study selected young and aged mice to take PBS or NMN (200 mg/kg/day) for 10 consecutive days, and to take hormones on the 8th and 10th days to perform superovulation and detect NAD+ levels. Significantly lower levels of NAD+ were detected in aged oocytes compared to young oocytes; whereas significantly higher levels of NAD+ were detected in oocytes of aged mice supplemented with NMN.

 

The study assessed oocyte morphology in young, aged and NMN+ aged mice and found that maternal aging significantly reduced the number of ovulated oocytes and the ratio of mature oocytes and increased the incidence of oocyte fragmentation. Conversely, NMN supplementation significantly ameliorated the aging-induced deficits in oocyte number and morphology.

 

The study assessed follicular development through ovarian slices and observed that follicles in aged mice were severely degenerated at different developmental stages. NMN supplementation increased the number of antral follicles to a certain extent, and the number of ovulated oocytes increased in aged mice after NMN supplementation.

 

Consistent with an increase in the number of mature oocytes with normal morphology, fertility in aged mice was also enhanced by NMN administration.

 

No developmental abnormalities were observed in both sexed pups of young, aged and NMN+ aged mice as assessed by body weight and organ weight. These observations suggest that NMN can partially restore the number and morphology of aged oocytes by increasing NAD+ levels, improving animal fertility.

 

2.       NMN supplementation restores meiotic maturation of aged oocytes

 

In vitro culture of germinal vesicle (GV) oocytes isolated from young, aged and NMN+ aged mice showed a considerably higher incidence of abnormal spindle/chromosomal structures in aged oocytes compared to controls, but decreased after NMN supplementation. These results suggest that NMN is able to effectively enhance the maturation capacity of aged oocytes by maintaining the correct spindle/chromosomal structure.

 

3.       NMN supplementation enhances the fertilization ability of aged oocytes

 

Experiments performed in vitro fertilization of oocytes in different states, and the results showed that most young oocytes could be fertilized and developed into 2-cell embryos, while the fertilization rate of aged oocytes was significantly lower than that of young oocytes, and NMN supplementation effectively The fertilization rate of aged oocytes was improved, and the blastocyst formation rate of fertilized eggs of aged mice was significantly promoted. These results suggest that NMN enhances the fertilization capacity of senescent oocytes and promotes their embryonic development.

 

4.       NMN supplementation restores mitochondrial function in aged oocytes

 

In aging oocytes, a large number of mitochondria are abnormally distributed, suggesting that mitochondrial function may be impaired as oocytes age. More than 40% of these aged oocytes exhibited mislocalized mitochondria, which decreased to 24% after NMN supplementation. At the same time, measuring ATP levels in mouse cells in different states, the results showed that compared with young oocytes, ATP levels in aged oocytes decreased significantly, but recovered after NMN supplementation. Therefore, mitochondrial dysfunction induced by oocyte aging can be ameliorated by NMN supplementation.

 

5.       NMN supplementation reduces ROS levels to inhibit DNA damage and apoptosis in aged oocytes

 

Mitochondrial dysfunction is responsible for ROS production and oxidative stress, and high levels of ROS often lead to DNA damage and apoptosis. Experiments detected ROS levels in different states of mice, and found that aged oocytes showed stronger ROS signals than young oocytes, and maternal aging led to a higher incidence of DNA damage and apoptosis in oocytes. NMN supplementation effectively reduced the accumulated ROS in aged oocytes and alleviated oocyte apoptosis.

 

This study demonstrates that NMN supplementation can improve the quality of aged oocytes, enhance the fertilization capacity of aged oocytes, and inhibit ROS-induced apoptosis of aged oocytes, which provides a basis for the application of NMN to improve fertility and assisted reproductive technology in advanced women. provides a theoretical basis for its effectiveness.

 

References:

[1]       庶正康訊(北京商務諮詢有限公司、天貓國際. NMN 品類發展白皮書 2020[R].

[2]       Miao Y , Cui Z , Gao Q , et al. Nicotinamide Mononucleotide Supplementation Reverses the Declining Quality of Maternally Aged Oocytes - ScienceDirect[J]. Cell Reports.

[3]       https://ars.els-cdn.com/content/image/1-s2.0-S2211124720309724-mmc1.pdf

2022年5月6日 16:12
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