NMN Increases Maternal Egg Quality，Number，and Fertilization Ability
NMN 提高母體卵子的質量、數量和受精能力
Nicotinamide mononucleotide (NMN) supplementation improves oocyte quality from naturally aged mice by restoring nicotinamide adenine dinucleotide (NAD+) levels.
煙酰胺單核苷酸 (NMN) 補充劑通過恢復煙酰胺腺嘌呤二核苷酸 (NAD+) 水平來改善自然衰老小鼠的卵母細胞質量。
(frentusha | iStock)
By Jonathan D. Grinstein，Ph.D.
Published: 12:16 p.m. PST Aug 11，2020 | Updated: 5:02 p.m. PST Oct 8，2020
An oocyte is the very beginning of human life—in the simplest of terms，it is an immature egg cell that eventually matures and becomes an ovum，or egg. However，as women age，there is a decline in oocyte quality，and effective approaches to improve oocyte quality remain sparse.
卵母細胞是人類生命的最開始——用最簡單的話來說，它是一個未成熟的卵細胞，最終成熟並成為卵子或卵子。然而，隨著女性年齡的增長，卵母細胞質量下降，改善卵母細胞質量的有效方法仍然很少。
A study in Cell Reports found that giving the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide mononucleotide (NMN) to mice effectively improves the quality of maternally aged oocytes. This study provides a potential strategy to improve the reproductive outcome of women of advanced maternal age. 『Our work expounds a theoretical basis for application of NMN to improve the fertility of aged women and the efficiency of artificial reproductive technologies,』 stated the researchers in their study.
Cell Reports 的一項研究發現，給小鼠註射煙酰胺腺嘌呤二核苷酸 (NAD+) 前體煙酰胺單核苷酸 (NMN) 可有效改善母體老化卵母細胞的質量。這項研究提供了一種潛在的策略來改善高齡產婦的生殖結果。研究人員在他們的研究中說：『我們的工作為應用 NMN 提高老年婦女的生育能力和人工生殖技術的有效性奠定了理論基礎。』
Supplementation of nicotinamide mononucleotide (NMN) efficiently improves the quality of oocytes from naturally aged mice by recovering nicotinamide adenine dinucleotide (NAD+) levels.
補充煙酰胺單核苷酸 (NMN) 通過恢復煙酰胺腺嘌呤二核苷酸 (NAD+) 水平，有效提高自然衰老小鼠卵母細胞的質量。
NMN supplementation not only increases ovulation of aged oocytes，it also enhances their fertilization ability. These findings reveal that NMN supplementation is a feasible approach to protect oocytes from advanced maternal age-related deterioration，contributing to the improvement of the reproductive outcome of aged women and assisted reproductive technology.
NMN 補充劑不僅可以增加老化卵母細胞的排卵，還可以提高它們的受精能力。這些發現表明，補充 NMN 是保護卵母細胞免受晚期母體年齡相關衰退的可行方法，有助於改善老年婦女的生殖結果和輔助生殖技術。
High-quality oocytes，a prerequisite for successful fertilization and subsequent embryonic development，are the material basis for the onset of life. In most mammals，female reproductive aging is particularly defined by a prominent decline in the quantity and quality of oocytes and the fluid-filled sacs that contain them (i.e.，ovarian follicles). Low-quality oocytes are a common and insurmountable problem for women with advanced maternal age and the main cause of the suboptimal reproductive outcomes. Despite the significance of the problem，strategies to sustain oocyte quality with age have been poorly explored.
高質量的卵母細胞是成功受精和隨後胚胎發育的先決條件，是生命開始的物質基礎。在大多數哺乳動物中，女性生殖衰老的具體定義是卵母細胞和包含它們的充滿液體的囊《即卵巢卵泡》的數量和質量顯著下降。低質量卵母細胞是高齡產婦常見且難以克服的問題，也是導致生育結果不佳的主要原因。盡管這個問題很重要，但隨著年齡的增長維持卵母細胞質量的策略研究很少。
NAD+ is a key element in metabolism and a critical regulator of diverse physiological processes，including genomic stability and cell survival. It has been reported that NAD+ levels decrease with age across many tissues and are implicated in a variety of diseases related to aging. Therefore，recovery of NAD+ levels is likely to be an effective anti-aging intervention.
NAD+ 是新陳代謝的關鍵元素，也是多種生理過程的關鍵調節劑，包括基因組穩定性和細胞存活。據報道，許多組織的 NAD+ 水平會隨著年齡的增長而下降，並且與多種與衰老相關的疾病有關。因此，恢復 NAD+ 水平可能是一種有效的抗衰老幹預措施。
NMN is a key precursor to NAD+ and administration of it can boost NAD+ content in cells. Accumulating evidence has shown that enhancing NAD+ biosynthesis by treatment with NMN in aged mice reverses age-related dysfunction in multiple organs. Although great progress has been made in the application of NMN toward aging，the effect of NMN on female reproductive aging has not been fully determined.
NMN 是 NAD+ 的關鍵前體，其給藥可以提高細胞中 NAD+ 的含量。越來越多的證據表明，通過用 NMN 治療老年小鼠來增強 NAD+ 生物合成可以逆轉多個器官中與年齡相關的功能障礙。盡管 NMN 應用於衰老方面取得了很大進展，但 NMN 對女性生殖衰老的影響尚未完全確定。
Previous research reports that the NAD+ levels decreased in oocytes from maternally aged mice but could be recovered by NMN administration to improve the quality of these oocytes. NMN supplementation to some extent increased the number of ovarian follicles，ovulated oocytes，and matured oocytes with less fragmentation.
先前的研究報告稱，母體衰老小鼠卵母細胞中的 NAD+ 水平有所下降，但可以通過施用 NMN 來恢復，以提高這些卵母細胞的質量。 NMN補充劑在一定程度上增加了卵巢卵泡、排卵卵母細胞和成熟卵母細胞的數量，碎片較少。
Effect of NMN Supplementation on NAD+ Content and Quality of Maternally Aged Oocytes.
NMN 補充劑對母體老化卵母細胞 NAD+ 含量和質量的影響。
In their study，the investigators observed that maternal aging dramatically reduced the number of ovulated oocytes and the rate of matured oocytes but increased the incidence of fragmented oocytes–defective immature egg cells that break apart and fail，ultimately resulting in their death. However，when the investigators supplemented the aged oocytes with NMN to restore NAD+ levels，they observed an enhanced maturation rate and amelioration of defects in the number and fragmentation of aged oocytes. In addition，they observed that maternal aging severely impaired follicle development and that NMN supplementation increased the number of follicles.
在他們的研究中，研究人員指出，母親衰老會顯著減少排卵卵母細胞的數量和成熟卵母細胞的比率，但會增加卵母細胞碎片的發生率——有缺陷的未成熟卵子會破裂和失敗，最終導致它們死亡。然而，當研究人員用 NMN 補充老化卵母細胞以恢復 NAD+ 水平時，他們觀察到成熟率增加，老化卵母細胞數量和碎片化缺陷得到改善。此外，他們觀察到母親衰老嚴重損害卵泡發育，補充 NMN 會增加卵泡數量。
Importantly，the investigators found that NMN supplementation improved the fertilization ability of aged oocytes. They also observed that NMN supplementation markedly promoted the subsequent embryonic development of fertilized oocytes. Along these lines，the investigators saw an improved formation rate of blastocysts–a collection of cells formed in the early development of mammals–from fertilized oocytes from aged mice . These results demonstrate that NMN improves the fertilization ability of aged oocytes and promotes their subsequent embryonic development.
重要的是，研究人員發現補充 NMN 可以提高老化卵母細胞的受精能力。他們還觀察到補充 NMN 顯著促進了受精卵母細胞隨後的胚胎發育。沿著這些思路，研究人員觀察到胚泡的形成率有所提高——胚泡是哺乳動物早期發育過程中形成的細胞集合——來自老年小鼠的受精卵母細胞。這些結果表明，NMN 提高了老化卵母細胞的受精能力，並促進了它們隨後的胚胎發育。
Effect of NMN Supplementation on the Fertilization Ability and Embryonic Development of Aged Oocytes. (D) Representative images of early developing embryos in young，aged，and NMN-supplemented aged mice. Left，2-cell stage embryos; right，blastocysts–a rapidly dividing ball of cells consisting of an inner group of cells that will become the embryo and an outer group of cells that nourish and protect the embryo. The rates of (E) fertilization and (F) the formation of a structure in early mammalian development called the blastocyst in young，aged，and NMN-supplemented aged mice.
NMN補充劑對衰老卵母細胞受精能力和胚胎發育的影響。 (D) 年輕、年老和補充 NMN 的年老小鼠早期發育胚胎的代表性圖像。左圖，2 細胞期胚胎；對，囊胚——一個快速分裂的細胞球，由將成為胚胎的內部細胞群和滋養和保護胚胎的外部細胞群組成。 (E) 受精率和 (F) 早期哺乳動物發育中稱為胚泡的結構在年輕、年老和補充 NMN 的老年小鼠中的形成。
Finally，the investigators found that the mechanism by which NMN was working to revitalize aged oocytes was by restoring the distribution and function of the cell’s powerhouse，the mitochondria. They observed that NMN supplementation suppressed the accumulation of reactive oxygen species–unstable molecules that may cause damage to DNA，RNA，and proteins，which can result in cell death. Along these lines，the investigators observed that NMN supplementation reduced DNA damage and，ultimately，cell death.
最後，研究人員發現，NMN 使老化卵母細胞恢復活力的機制是通過恢復細胞發電站線粒體的分佈和功能。他們指出，補充 NMN 會抑制活性氧的積累——不穩定的分子會導致 DNA、RNA 和蛋白質受損，從而導致細胞死亡。通過這種方式，研究人員觀察到 NMN 補充劑減少了 DNA 損傷並最終減少了細胞死亡。
These finds offer a potentially effective approach to improve the fertility of aged females and to acquire more high-quality oocytes for assisted reproductive technology. 『Collectively，our data reveal that NMN supplementation is a feasible approach to protect oocytes from advanced maternal age-related deterioration，contributing to the improvement of reproductive outcome of aged women and assisted reproductive technology.』
這些發現為提高老年女性的生育能力和獲得更多用於輔助生殖技術的優質卵母細胞提供了一種潛在有效的方法。 『總的來說，我們的數據表明，NMN 補充劑是一種可行的方法，可以保護卵母細胞免受晚期母體年齡相關衰退的影響，有助於改善老年婦女的生殖結果和輔助生殖技術。』
原文參考：
https://www.nmn.com/news/nmn-oocyte-quality-and-fertilization-ability
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