This time, we are introducing a research paper reporting that NMN effectively improves the quality of oocytes (cells that develop into eggs) in aged mice. It is a fact that the aging of women strongly affects the quality of oocytes, making pregnancy and childbirth difficult, but there is no clear improvement method yet. However, NMN treatment may become a viable option.
Who Should Read This Column
✅ Those who are trying to conceive and want to enhance the fertilization ability of their eggs
✅ Those who have been pointed out by medical institutions that their egg quality is low
✅ Those undergoing or about to start infertility treatment
✅ Those who want to start trying to conceive without straining their bodies
✅ Those who do not want to give up on pregnancy and childbirth even at an advanced age
✅ Those who wish to conceive naturally as much as possible
The Quality of Oocytes is Crucial for Fertility
The egg that governs fertility is formed through the process of oogonium → primary oocyte → first meiotic division → secondary oocyte → second meiotic division → egg. Once fertilization is established, the egg becomes a fertilized egg and pregnancy is confirmed.
However, only a small percentage of oocytes mature into eggs, and most oocytes perish without maturing into eggs. The number of oocytes also decreases with age, from 7 million at 20 weeks of gestation to 2 million at birth. Typically, it decreases to 200,000 to 300,000 at puberty when menstruation starts, and the speed of reduction accelerates after age 37.
With aging, oocytes are thought to age within the ovaries, increasing chromosomal abnormalities, leading to a decline in oocyte quality. The decline in oocyte quality directly affects the quality of eggs, reducing the chances of natural conception. Research has shown that the probability of natural conception within six months at age 30 is 77%, but it drops to 62% after age 37 and to 29% at age 42.
Pregnancy is established by a combination of many conditions, so it cannot be said that the decline in egg quality is the sole cause of infertility. However, data from the Japan Society for Reproductive Medicine indicate that a decline in egg quality increases the proportion of eggs that cannot fertilize properly (infertility) and the possibility of miscarriage.
NMN Contributes to Cell Function Improvement. What About Oocytes?
NMN is converted to NAD+ in cells and is used to activate sirtuins (longevity genes) and mitochondria. NAD+ is an essential molecule for all living organisms to live, and the intake of NMN leads to an increase in the quantity and quality of NAD+. Therefore, NMN is expected to improve aging organs and functions.
So, can it also be effective for the quality of aged oocytes? If the quality can be improved, natural childbirth at an advanced age might not be a dream. The research paper introduced this time hypothesizes that NMN, which promotes the recovery of NAD+ levels, may be effective in improving the quality of aged oocytes. Experiments were conducted using aged mice.
Experimental Details
Young mice aged 6-8 weeks and aged mice aged 64-68 weeks were prepared and divided into the following three groups:
② Aged mice administered with PBS
③ Aged mice administered with PBS + 200 mg/day NMN per kg body weight
※NMN is administered intraperitoneally
※1: phosphate buffered saline, a reagent with buffering capacity that prevents large pH changes when chemicals are dissolved. Using PBS prevents phenomena where substances cause strong acids or alkalis when dissolved in physiological saline.
Ovulation was induced by administering ovulation-inducing agents (hormones) on the 8th and 10th days, then the condition of the oocytes was observed to investigate the effects of NMN administration in aged mice.
■ Evaluation of Oocytes
Observation of the number and percentage of oocytes in the three groups under a light microscope showed that aged mice administered with NMN had improved oocyte development rates due to increased NAD+ content in the oocytes, despite some follicular degradation.
The percentage of abnormal oocyte morphology also decreased. This suggests that NMN improved the reproductive capacity of aged mice by restoring NAD+ levels.
Additionally, aged mice administered with NMN showed improved meiotic ability and embryonic development of fertilized eggs. In other words, NMN is thought to enhance the fertilization capacity of aged oocytes while promoting embryo development. Furthermore, single-cell transcriptome analysis※2 revealed that NMN suppressed the accumulation of ROS※3 and DNA damage in aged oocytes by restoring mitochondrial function, thereby inhibiting apoptosis of oocytes.
※2: Comprehensive gene expression analysis at the single-cell level for understanding biological responses in more detail
※3: Reactive oxygen species, byproducts of the mitochondrial electron transport system with cytotoxicity that can cause cellular damage if excessively accumulated
Above: Mechanism of oocyte quality improvement by NMN administration (Left: Aged mouse without NMN administration / Right: Aged mouse with NMN administration)
※Graphs and photos are modified from the original paper.
NMN as a Beacon of Hope for Elderly Women Wishing for Pregnancy and Childbirth!?
This experiment showed that NMN supplementation might protect aged oocytes and contribute to the improvement of reproductive function and assisted reproductive technology (ART) for elderly women. NMN is confirmed to be highly safe for the human body, and it is considered to have no negative impact on the mother or child before or during pregnancy.
For those currently struggling with fertility treatment, as well as those planning to start trying to conceive, why not incorporate NMN into your fertility journey? NMN can be taken through supplements or drips, but supplements are cheaper and more convenient than drips to start trying to conceive.
However, excessive intake of any supplement can be counterproductive. It is recommended to consult a reliable medical institution to determine your optimal dosage before taking it.
【Reference】
Reference Paper: [Nicotinamide Mononucleotide Supplementation Reverses the Declining Quality of Maternally Aged Oocytes]
Journal & Volume / Cell Rep. 2020 Aug 4;32(5):107987.
Paper URL is here (PubMed)
https://pubmed.ncbi.nlm.nih.gov/32755581/