Resveratrol and Reproductive Health: How This Potent Antioxidant Supports Female Fertility With Age

Once a woman reaches her early- to mid-30s, it’s a common thought in the back of our heads that the clock is ticking if we want to have children biologically. We know that female fertility declines with age — but what if there was something we could do to extend our reproductive years? As many women are now waiting longer and longer to start families, doctors and patients alike are searching for ways to delay this age-related decline in female fertility. From developing innovative technologies like in vitro fertilization (IVF) to identifying compounds that can restore our reproductive health, it may soon be possible to maintain successful pregnancies well into our 40s, 50s, and beyond.  

Researchers out of Nanjing, China, may have found one such way to beat this biological race against time, with the compound resveratrol — a well-known antioxidant primarily found in red wine and grapes. In a recent study published in the journal Molecules, Abbasi and colleagues show how resveratrol prevents egg cells from exhibiting the typical signs of aging. By boosting antioxidant activity and supporting mitochondrial health — the cells’ energy production centers — resveratrol improves egg quality and could prove to be a novel approach for protecting and prolonging fertility with advancing maternal age. 

Two Tales of Aging Egg Cells

Beginning in the third decade of a woman’s life, both the number of viable egg cells and the chances of becoming pregnant naturally will decrease year after year. Older oocytes — the term for immature egg cells before they fully mature into eggs that can be fertilized — have significantly impaired ovulation rates and maturation, leading to low fertility. These aged egg cells also exhibit follicular loss — the small fluid-filled ovarian sacs that house oocytes — and dysfunction in the processes necessary to properly mature and develop viable eggs into embryos.  

For reasons varying from advancing age to various medical conditions, many women look to assisted reproductive technologies like IVF to aid in getting pregnant. However, IVF has only about a 50% success rate, due in part to post-ovulatory aging — a degradation process that takes place in the short timeframe between ovulation and potential fertilization. If an egg is not fertilized in the earlier window, the oocyte degrades in quality, and poor embryonic development after fertilization with high rates of IVF failure occurs. So, women of advancing age attempting pregnancy have two roadblocks to overcome — the typical age-related loss of viable egg cells, and the post-ovulatory aging that occurs if they use assisted reproductive technologies.

Oxidative Stress Obliterates Oocytes

It’s not fully understood why oocytes take such a hard hit several decades before other cells and organs in the body tend to decline. However, it’s thought that high levels of oxidative stress — excessive amounts of harmful compounds called reactive oxygen species (ROS) with inadequate antioxidants to neutralize them — combined with reduced mitochondrial function plays a prominent role. 

Oxidative stress markedly reduces levels of our body’s most abundant antioxidant, glutathione, while allowing ROS to accumulate and damage our cells and DNA. This imbalance triggers apoptosis — a process that ultimately causes cell death. Some apoptosis is normal and undeniably good for us, as it can remove unneeded or unwanted cells. However, in the case of fertility, higher apoptosis rates would prematurely deplete the oocyte supply and reduce reproductive capabilities, as these cells aren’t able to renew themselves.

Mitochondria also play a vital role in regulating the function and survival of oocytes, but these cellular energy powerhouses are also highly susceptible to ROS-induced damage. Therefore, antioxidant compounds like resveratrol may provide a safe and effective strategy for combating the loss of antioxidant and mitochondrial function that contribute to oocyte aging. 

Restoring Reproductive Health With Resveratrol

In this study, Abbasi and colleagues looked at the effects of resveratrol on porcine (pig) oocytes, as these cells have similar developmental and physiological properties as human oocytes. The research team found that adding resveratrol to aged porcine oocytes significantly alleviated oxidative stress markers compared to untreated aged cells. Resveratrol also boosted glutathione levels and the genetic activity of antioxidant-related enzymes, including catalase, superoxide dismutase, and glutathione peroxidase. 

The resveratrol treatment reduced apoptosis rates in the oocytes and regulated mitochondrial membrane potential (MMP) — a key indicator of mitochondrial health. As a loss of MMP is a signal of cellular stress, low MMP is linked to increases in apoptotic cell death. Lastly, the porcine oocytes exhibited increased growth rates and improved structural markers, indicating more functional cells. 

Don’t Put All Your Eggs in One Basket

In all, these results suggest that resveratrol supplementation may be a strategy for fighting back on both the age- and IVF-related decline in oocyte health that contributes to low female fertility. While promising, more studies are needed, as we don’t know if the same effects would occur in humans or human cells — so don’t put all of your eggs in the resveratrol basket yet.

One study with middle-aged mice exhibited comparable results to the present research, showing that short-term resveratrol injections reduced oxidative stress-induced damage in post-ovulatory oocyte aging. Similarly, a longer-term study found that female mice supplemented with resveratrol for 12 months had significant improvements in the number and quality of viable oocytes, suggesting that resveratrol does support fertility with age.

The authors conclude in their paper, “Collectively, our findings lead to the evidence that [resveratrol] may be one of the important constituents in improving the oocyte quality by delaying the anti-aging effects through its antioxidant properties on porcine oocytes.”

References: 

Abbasi B, Dong Y, Rui R. Resveratrol Hinders Postovulatory Aging by Modulating Oxidative Stress in Porcine Oocytes. Molecules. 2021;26(21):6346. Published 2021 Oct 20. doi:10.3390/molecules26216346

Liang QX, Lin YH, Zhang CH, et al. Resveratrol increases resistance of mouse oocytes to postovulatory aging in vivo. Aging (Albany NY). 2018;10(7):1586-1596. doi:10.18632/aging.101494

Liu M, Yin Y, Ye X, et al. Resveratrol protects against age-associated infertility in mice. Hum Reprod. 2013;28(3):707-717. doi:10.1093/humrep/des437