New study determines the key role of Endometriosis in women infertility. A possible solution: Anti-oxidants could reverse free-radicals' impact on oocyte DNA damage

Posted By Braverman IVF & Reproductive Immunology || 22-Nov-2016

A recent study published last week in Nature Scientific report revealed that infertility related to endometriosis may be due to oocyte (egg) DNA damages induced by oxidative stress.

Most importantly, the study further suggested that oxidative stress (the main cause of oocyte DNA damage) could be reversed using anti-oxidants such as melatonin and resveratrol thus rescuing the oocyte and leading to its development and maturation to give rise to a fertilizable egg.

Oxidative stress disrupts oocyte maturation and blocks its development

Endometriosis is a benign gynecologic disorder that affects 5–10% of women of reproductive age worldwide and is characterized by the presence of endometrial cells outside the endometrium.

During its maturation, the oocyte (egg) is exposed to follicular fluid filling the antral cavity as seen in the Figure 1 below.

In patients with endometriosis, follicular fluid (FF) is characterized by pro-inflammatory factors such as IL-6 or TNF-α (1), with increased levels of oxidative stress as seen by higher levels of reactive oxygen species or ROS (2). This leads to poor egg quality (DNA damage) and lower mature oocyte and fertilization rate in these patients (3).

Figure 1: Mature follicle

To assess the effects of oxidative stress on oocyte development, the authors of the study exposed in vitro, immature healthy mouse oocyte to follicular fluid from women affected by endometriosis (ENDO-FF). They monitored the oocyte development and compared it to immature mouse oocyte cultured with follicular fluid from healthy women (controls patients not affected by endometriosis).

Results showed that Endo-FF induced:

  • Higher levels of ROS in the mouse oocyte
  • Higher levels of DNA damage in the mouse oocyte
  • Decrease or a delay in oocyte maturation as compared to controls

Oocyte maturation was impaired by Endo-FF and the oocytes’ development was blocked.
Interestingly, the oocyte maturation was blocked at a very specific development stage (metaphase I arrest) where a sensor for DNA damage (Spindle Assembly Check point/Dna Damage Response) assesses the DNA integrity and blocks the oocyte maturation through the activation of a protein (ATM kinase).
The study showed that ROS directly activates this blocking protein to stop oocyte development.

Further, the authors showed that oocyte maturation could be rescued by inhibiting or lowering ROS levels using resveratrol and melatonin in the culture medium.

It is very important to note that the noxious effects of ROS and pro-inflammatory factors presents in the follicular fluid of ENDO patients would be even more accentuated in human ovary where oocytes are exposed to follicular fluid at higher concentrations and for longer periods of time than in the current study.

Therefore, the pathway is highly susceptible to diseases such as endometriosis, but also to any other diseases that could elevate ROS levels such as in PCOS patients (4).

Endo-Optimize supplement: the best solution to counteract oxidative stress induced-DNA damage and optimize your egg quality

Reducing oxidative stress in the oocyte is of clinical importance when treating sub-fertility in endometriosis patients or in any patients whose oocyte quality is affected by high levels of oxidative stress such as in PCOS or Correctible Reoccurring Aneuploid Conversion Syndrome or CRACS patients (For more information, read our blog on CRACS).

To this end, we developed a dietary supplement “The Endo-Optimize” containing many ingredients with beneficial actions on reducing ROS and free-radicals’ production and enhancing oocyte maturation such as melatonin (5) and resveratrol (6).
In addition, this all in one pill contains many other ingredients enhancing mitochondrial activity (a key component in oocyte development) and reducing inflammation thus allowing optimal microenvironment for the oocyte development and maturation (For more information read our blog on the “Endo-Optimize supplement” ).

Over the years, we have seen tremendous improvement in oocyte and embryo quality as well as great success in women with endometriosis who have used the supplements contained in the Endo-Optimize.

As pioneer in the field of Reproductive Immunology, we are consistently developing cutting-edge and innovative strategies based on the latest advances in clinical and basic research to better address your fertility issues and help you achieve a healthy pregnancy.


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