Administration of nicotinamide mononucleotide improves oocyte quality of obese mice

Abstract

Objectives: Obesity has become a common health concern around the world. Maternal obesity could cause poor reproductive outcomes due to chronic ovarian inflammation and decreased oocyte quality. However, the strategies to improve the poor reproductive outcomes of obese females have not been fully studied. In this study, we aimed to explore the effects and underlying mechanisms of nicotinamide mononucleotide (NMN) on oocyte quality and reproductive performance of obese mice. Materials and Methods: The obese mouse model was established by feeding high-fat diet which was confirmed by body weight record, fasting blood glucose test and oral glucose tolerance test. The expression of ovary development related genes and inflammation related genes, including Lhx8, Bmp4, Adgre1, Ccl2, TNF-α, Gal-3, Clec10a and IL-10 in ovaries and the expression of Bax and Sod1 in oocytes were detected using quantitative reverse transcription PCR (RT-qPCR). The adipose size of abdominal fat tissue was determined with haematoxylin and eosin (H&E) staining. Immunofluorescence staining was performed to measure the ROS level, spindle/ chromosome structure, mitochondrial function, actin dynamics and DNA damage of oocytes. Results: The administration of NMN restored ovarian weight and reduced the adipose size of abdominal fat tissue and ovarian inflammation in high fat diet (HFD) mice. Furthermore, NMN treatment improved the oocytes quality partially by restoring the mitochondrial function and actin dynamics, reducing meiotic defects, DNA damage and ROS level and lipid droplet distribution of oocytes in HFD mice. On the long-term effect, NMN restored offspring body weight of HFD mice. Conclusion: NMN could improve the oocyte quality of HFD-induced obese mice. | INTRODUCTIONObesity has become a major global health issue with the rise of overweight. 1 Maternal obesity is closely related to poor reproductive outcomes, including early pregnancy failure, preeclampsia and neonatal conditions. 2,3 Chronic inflammation caused by obesity impacts ovarian physiology and impairs reproductive health. 4 Multiple studies have found that the oocyte quality of obese mice is impaired, due to

Effects of β-Nicotinamide Mononucleotide, Berberine, and Cordycepin on Lipid Droplet Content and Developmental Ability of Vitrified Bovine Oocytes

“…The results showed that NMN could restore this balance of mitochondrial fusion and fission by upregulating MFN1 and MFN2 and downregulating DRP1 and FIS1 (Figure 5), similar to previous researches [19,59]. Furthermore, NMN has been proven to reduce the damages of stress such as high-fat diet [40], senescence [33], toxicants [61], and heat stress [30], and improve the quality of oocytes in mice [61] and pigs [30] by reducing meiotic defects, rescuing mitochondrial function, and eliminating the accumulated ROS to suppress apoptosis.…”

“…Wang and colleagues [40] found that after treatment with NMN, the lipid droplet content in mouse oocytes significantly decreased. Similarly, our results in Figure 1B indicated that NMN treatment also led to a significant reduction in lipid droplet content in bovine oocytes, which could be attributed to the reduced expression of genes such as FABP3, SREBP1, and PPARG (as shown in Figure 2).…”

Nicotinamide mononucleotide induces autophagy and ferroptosis via AMPK/mTOR pathway in hepatocellular carcinoma

“…NMN safely and effectively elevated NAD + metabolism in healthy middle‐aged adults 31 . In addition, long‐term administration of NMN restored offspring body weight of mice with high fat diet 32 . In our study, NMN treatment had no effect on the body weight of mice during animal experiments.…”

Nicotinamide Mononucleotide improves oocyte maturation of mice with type 1 diabetes

“…Moreover, NMN could enhance the developmental capability of vitrified bovine oocytes by decreasing the ROS level, reducing endoplasmic reticulum (ER) stress, improving mitochondrial function, and inhibiting apoptosis [ 25 ]. Recently, NMN has been proved to exert the beneficial effects on oocytes of aging mice and the mice with obesity [ 26 – 28 ]. Despite the current progress for NMN in improving the quality of oocytes from aging mice and the mice with obesity, the effect of NMN on the oocyte quality of the mice with type 1 diabetes has not been determined.…”