New Hope for Advanced-Age Fertility! Pterostilbene in Blueberries Reverses Oocyte Aging

With the postponement of the age at marriage and childbearing, infertility in women of advanced reproductive age (ARA) has become an increasingly prevalent clinical issue, and the decline in oocyte quality constitutes a pivotal limiting factor. Fortunately, a recent study conducted by a research team from Juntendo University, Japan, has provided promising insights into this challenge.

Core Dilemma: Oocyte Senescence Impairs Fertility, Resveratrol Has Limitations

Oocyte quality deteriorates with advancing age, primarily attributed to mitochondrial dysfunction and elevated chromosomal aneuploidy rates. Although natural polyphenols such as resveratrol exhibit potential for ameliorating oocyte aging, their clinical application is constrained by low bioavailability and the potential to inhibit endometrial decidualization.

Novel Discovery: Pterostilbene Emerges as a Modulator of Oocyte Senescence

The research team published a paper in the journal Aging demonstrating that pterostilbene can reverse age-associated oocyte quality decline via a unique mitochondrial regulatory mechanism, without adverse effects such as decidualization inhibition. Pterostilbene, a methoxylated derivative of resveratrol, is naturally present in blueberries, grapes, and Pterocarpus santalinus (Indian rosewood). Its lipophilic structure confers significantly higher in vivo stability and bioavailability compared to resveratrol, along with potent antioxidant, anti-inflammatory, and anti-aging bioactivities.

Experimental Validation: Favorable Safety Profile, No Disruption to Murine Physiology

The team administered pterostilbene to aged mice for short-term (1 week) and long-term (22 weeks) durations, and observed no interference with the estrous cycle or body weight. The estrous cycle of the aged control group was prolonged to 9 days, whereas no significant difference was detected between the pterostilbene-treated group and the untreated aged group. Although the body weight of 47-week-old mice was higher than that of 25-week-old mice, pterostilbene intake of varying durations did not induce body weight fluctuations, confirming its favorable safety profile.

Reproductive Efficacy: Long-Term Administration Enhances Key Fertility Outcomes

Long-term pterostilbene administration significantly increased the ovulation count in aged mice, whereas short-term (1 week) and medium-term (6 weeks) administration failed to exert this effect. While it did not reverse the age-induced reduction in fertilization rate, the embryo implantation rate, live birth rate, and miscarriage rate were substantially improved. Notably, the implantation rate and live birth rate in the 22-week long-term administration group were restored to the levels observed in young mice. Embryo transfer experiments further verified that the offspring of the pterostilbene-treated group exhibited normal development, with no abnormalities in health status or reproductive capacity.

Mechanism of Action: Independent of Classical Pathways, Optimizes Mitochondrial Energetics

Serum analysis revealed a positive correlation between pterostilbene concentration and ovulation count, implantation rate, and live birth rate, along with a negative correlation with miscarriage rate. No association with the expression of Sirtuin family genes was observed, suggesting that its mechanism of action may be independent of the classical anti-aging pathway. In terms of oocyte mitochondrial function, pterostilbene significantly elevated mitochondrial membrane potential (ΔΨm) and adenosine triphosphate (ATP) levels without altering mitochondrial DNA (mtDNA) copy number, indicating that it improves oocyte quality by optimizing mitochondrial energy metabolism rather than increasing mitochondrial quantity.

Comparative Advantage: Superior to Resveratrol, Confirmed Clinical Safety

In vitro experiments demonstrated that pterostilbene, at concentrations ranging from 0.02 to 2.0 μM, did not inhibit the decidualization of endometrial stromal cells—a critical step in embryo implantation—whereas resveratrol has been previously reported to disrupt this process. This finding provides crucial evidence for the clinical safety of pterostilbene.

Conclusion: Natural Compound Exhibits Potential as an Anti-Aging Fertility Intervention

As a natural phytochemical in blueberries and other plants, pterostilbene enhances mitochondrial function, improves oocyte quality and pregnancy outcomes in aged mice, and poses no risks to body weight, estrous cycle, or offspring health. It also circumvents the limitations of resveratrol, demonstrating unique potential as an anti-aging fertility intervention. This discovery offers a novel perspective for the development of natural therapies for infertility in women of advanced reproductive age and provides a scientific basis for the exploitation of food-derived bioactive ingredients.

For further details, refer to the original study: https://doi.org/10.18632/aging.206287

Important Reminder：All content in this article is for general reference only and is provided solely to offer information support for practitioners in the nutrition and health industry. Descriptions related to efficacy are supported by corresponding data, but they do not represent claims or guidance for consumers. Content related to health, medical care, and technological applications is for reference only. For medical matters, please consult professional medical institutions and follow medical advice. This article does not provide any medical recommendations.