With age, our bodies accumulate damage, and oocytes aren’t an exception. Damages from reactive oxygen species to both oocytes and mitochondria, the cellular battery, are well known as the major contributing factors to the age-related decline in fertility, especially among women.

A plethora of antioxidants have been investigated as a way to protect oocytes and mitochondria from oxidative damage. We take a look at a study from Shandong University in China that investigated one of them, resveratrol.

In this laboratory study, the authors added resveratrol to the medium where the oocytes from women in their late 30s into mid-40s were cultured. This addition of resveratrol significantly improved the quality of these oocytes, opening up the possibility for interventions at different stages of the fertility journey - as well as women with egg quality issues due to common inflammatory conditions like endometriosis and PCOS.

Study Vitals

• Title: Resveratrol improves in vitro maturation of oocytes in aged mice and humans
• Authors: Mei-Ju Liu, Ai-Gang Sun, Shi-Gang Zhao, et al.
• Publication date: May 1, 2018
• Journal: Fertility & Sterility
• Study type: Experimental laboratory study 

Key Finding(s)

• Resveratrol improves in vitro maturation of oocytes retrieved from women between ages 38 and 45, as well as from mice.

Age, Mitochondria and Chromosomal Health of Oocytes

A substantial part of the age-related decline in female fertility is due to the decline in oocyte quality, which in turn derives from increasing dysfunctions of mitochondria. Mitochondria is an intra-cellular powerhouse that provides energy for the healthy development and functioning of all cells, including oocytes.

Oocytes, being the largest cells in the human body, require proper functioning of mitochondria, and this is particularly crucial during meiosis – the process in which germ cells divide to produce oocytes with just one copy of the maternal chromosome. During meiosis, the two copies of the chromosome are pulled apart by a structure called meiotic spindle. This intricate process that ensures oocytes’ chromosomal health (ploidy) needs all cellular functions to align properly, and the energy to drive this meiotic spindle is one part of that equation, as this 2020 review summarizes well.

As we age, our mitochondria accumulate damages from oxidative stress, and slowly lose their ability to produce cellular energy at the optimal level, leading to more aneuploidy (chromosomal abnormalities) in oocytes. This increase in abnormal embryos contributes to the fertility decline in women that starts accelerating in our mid-30s. Scientists have identified various antioxidants to protect mitochondrial DNA from oxidative damage. Resveratrol is one of these antioxidants. (Another well-researched antioxidant is Coenzyme Q10, or CoQ10.)

Why Resveratrol?

Resveratrol is a natural, plant-derived polyphenolic compound. Found in abundance in grape skins and seeds, resveratrol protects plants against pathogens like bacteria and fungi. In the last few decades numerous studies have explored resveratrol’s ability to act as a strong antioxidant, anticarcinogenic, antiproliferative and anti-inflammatory agent in animals and humans.

This 2018 study we are looking at applied this knowledge to the maturation process of oocytes in vitro, to see if addition of a tiny amount - 1.0 μm - of this polyphenol to the culture medium of oocytes could improve the chances of their healthy development. Investigating the hypothesis in both humans and mice, the authors found that resveratrol enhanced spindle morphology and chromosomal alignment in oocytes, and posited that oocytes (and embryos), particularly vulnerable to oxidative stress during in vitro culture, may benefit from addition of resveratrol in the culture media.

What This Means for You & Your Fertility

Like this study, much of the research has focused on the effects of resveratrol on oocytes, sperm and embryos in lab settings, as well as the genetic and molecular mechanisms that drive those effects. Establishing a causal relationship between dietary changes to increase resveratrol intake and fertility still needs work.

Since the hypothesis is that resveratrol may protect mitochondria and oocytes from oxidative stress throughout their months-long maturation journey, more studies on dietary intake of resveratrol well before pregnancy would be welcome. The most effective dosage for fertility purposes, as well as the delivery mechanism to maximize bioavailability, are two other aspects of resveratrol worth further exploration.

There are some studies, however, as summarized in this 2019 review, that indicate including resveratrol in your diet may help your oocytes stay in shape, by activating a protective factor against oxidative stress, called SIRT1. A combination of resveratrol and melatonin, a hormone released by the pineal gland in our brains during sleep, has also been investigated for women with PCOS and endometriosis – both inflammatory conditions with fertility implications.

Does this mean that we should reach for that glass of red wine, the best-known source of resveratrol? Possibly not – the amount of resveratrol in average red wine is estimated to be around 2-4 mg per liter, likely not enough to make a significant difference.

As always, we strongly recommend everyone to discuss resveratrol supplementation for fertility purposes with a qualified healthcare provider first. If you – or your healthcare team – have any questions, please reach out to us. We are with you.