A recent study in mice investigated the effects of short- and long-term NMN supplementation on age-related fertility decline and ovarian health.
Key Points
NMN supplementation showed significant effects in aged female mice:
- Increased ovarian NAD+ levels and ovulation quality
- Improved hormone secretion, and reduced oxidative stress and inflammation
- Increased ovarian reserve
- Boosted fat storage and mitochondrial function
- Improved overall ovarian health
Effect of NMN on Ovarian Health and Fertility Evaluated in Aged Mice
Young (2-month-old) and aged (12-month-old) mice were utilized in two experiments to determine the effects of NMN treatment on ovarian health.
The first experiment evaluated the effects of short-term (10-day) treatment delivered intraperitoneally:
- Young mice: received saline
- Aged control mice: received saline
- Aged + NMN mice: received NMN (500 mg/kg)
The second experiment investigated the effect of long-term (8 weeks) treatment delivered through drinking water:
- Young mice: received saline
- Aged control mice: received saline
- Aged + NMN mice: received NMN (2 g/L)
Short-Term NMN Improved Ovarian NAD+ Levels and Ovulation Quality
Short-term NMN (i.p., 500 mg/kg) supplementation significantly increased NAD+ ovarian levels in aged mice.
“NMN supplementation effectively countered the decrease in ovarian NAD+ concentration in aged mice.”
The number of eggs produced in aged mice was increased compared to those not treated with NMN.
This graph shows that aged mice (pink bar) produced significantly fewer eggs (oocytes) than young mice (yellow bar), but when given NMN (purple bar), the aged mice produced significantly more eggs compared to untreated aged mice.
The overall quality of the eggs produced in NMN-treated aged mice was improved:
- Reduced defects in the oocytes
- Improved mitochondrial function
- Reduced production of damaging free radicals
Long-Term NMN Improved Health Status and Ovarian Reserve of Aging Mice
NMN supplemented in drinking water for 8 weeks improved the ovarian reserve and general health of the aged mice:
- Improved ovarian hormone secretion: ↑ estrogen and anti‐Müllerian hormone (AMH); ↓ follicle‐stimulating hormone (FSH)
- Reduced oxidative stress markers: ↓ reduced glutathione (GSH) and malondialdehyde (MDA)
- Lowered inflammation: ↓ proinflammatory markers: (IL-1β and TNF-α)
“The results indicate that NMN treatment improved the overall health status of the mice and enhanced ovarian hormone secretion.”
Additionally, NMN helped preserve immature follicles (eggs) and increased the number of follicles that could fully develop
“Long‐term supplementation with NMN significantly improved the ovarian reserve in aged mice.”
Enhanced Fat Storage and Mitochondrial Function in Cells Supporting Egg Growth
NMN increased the number of fat droplets in cells that support egg development during later stages, boosting their energy supply and promoting healthier egg development.
This figure shows that fat content in granulosa cells, which support egg growth, was reduced in aged mice (pink bar) compared to young mice (yellow bar). However, NMN treatment (purple bar) restored fat content in aged mice to levels similar to the younger group.
Additionally, NMN restored mitochondrial structure and improved energy production, which had decreased with age.
“These data indicate that NMN treatment significantly alters the ultrastructure of mitochondria in granulosa cells, a change that has a positive effect on follicle development and maturation.”
NMN Improved Overall Ovarian Health
NMN treatment helped restore the size and function of the ovaries, which had decreased with age.
“Aging significantly reduced the area of the mouse ovarian sections and that NMN treatment effectively reversed ovarian atrophy.”
Ovarian tissue scarring (fibrosis) and abnormal fat accumulation were prevented in aged mice treated with NMN.
“These findings suggest that NMN treatment reverses the changes that otherwise occur in the tissue composition of aging mouse ovaries and that it inhibits fibrosis”
NMN also increased the number and area of mitochondria in the ovarian tissue.
“These data suggest that NMN may reverse ovarian aging by regulating mitochondrial function and lipid metabolism.”
Conclusion
NMN restored ovarian NAD+ levels and improved the quality and quantity of ovulated eggs.
“Ovarian nicotinamide adenine dinucleotide levels decline with age, but NMN administration significantly restores these levels, preventing ovarian atrophy and enhancing the quality and quantity of ovulated oocytes.”
Hormone secretion improved, while oxidative stress and inflammation were significantly reduced.
“Improvements in serum hormone secretion and antioxidant factors, along with decreased expression of proinflammatory factors, were observed.”
NMN also enhanced fat storage and mitochondrial function in cells that support cell growth.
“NMN significantly alters the density and morphology of lipid droplets and mitochondria in granulosa cells.”
Overall, ovarian health and reproductive potential improved.
“NMN supplementation could improve the health status of aging ovaries and enhance ovarian reserve, offering new insights into addressing fertility challenges in older women through assisted reproductive technology.”