Matrix metalloproteinase in the uterine cavity

Posted By Braverman IVF & Reproductive Immunology | 19-March-2019

Learn how Resveratrol can also help improve your chances of pregnancy

A recent study published in the Journal Gynecological Endocrinology showed the therapeutic benefits of resveratrol in patients with endometriosis, that significantly reduces the expression of matrix metalloproteinase MMP-2 and MMP-9, proteins over-expressed in endometriosis and hallmark of inflammation.

Matrix metalloproteinase also known as gelatinases are involved in uterine tissue remodeling during the menstrual cycle and during the critical step of embryo implantation (1).

Indeed, the dysregulation of MMPs in addition to progesterone resistance in endometriosis patients may be one of the causes for reccurent implantation failure in this patient ‘population (2).

Resveratrol is a polyphenolic compound isolated from the skin of red grapes and berries and found in red wine.

In addition to its anti-inflammatory properties, it is a natural aromatase inhibitor, an enzyme involved in the synthesis of estradiol and has also antiproliferative and anti-oxidant properties.

In the above-mentioned study, 34 infertile patients with endometriosis stage III or IV, were randomly placed on 400mg resveratrol twice a day for 12-14 weeks or left untreated as controls.

Patients treated with resveratrol saw a -20% reduction in both MMPs expression levels in their serum and endometrial fluids.

Previous studies have shown that MMP-2 (3) and MMP-9 (4) were significantly increased in the eutopic endometrium of women with endometriosis as compared to healthy women, a similar profile was also noted in the serum and endometrial fluid of women with endometriosis (5).

MMPs are enzymes able to degrade the extra cellular matrix thus allowing endometrial tissue to implant leading to endometriosis.

By repressing their expression, resveratrol limits the adhesion of endometriotic lesions. The benefits of resveratrol on endometriosis are multiple and have been described in one of our previous blog.

Resveratrol appears to be effective in counteracting the development of endometriosis through:

  • its antiangiogenic properties
  • anti-inflammatory properties
  • inhibiting the adhesion and proliferation of endometriotic lesions
  • reducing the oxidative stress
  • which leads to a reduction in the number and the volume of lesions

    By repressing MMP2 and MMP-9 endometrial expression, resveratrol may also play a role in promoting adequate endometrial receptivity thus increasing chances for a successful implantation.

    A study (6) showed elevated levels of activity of the gelatinases MMP-2 and MMP-9 (reflecting an inflammatory process) in the uterine flushing fluid of women with reccurent implantation failure (RIF) as compared to fertile women.

    When women were treated with antibiotics and/or corticosteroids for 2 weeks, MMP-2 and MMP-9 activity significantly decreased. Most importantly, pregnancy rate in patients treated for high MMPs activity (resulting in lower MMPs activity) was higher (42%) than in the control group with elevated MMPS activity (26.6%).

    Further the miscarriage rate was also lower in the treated group (28.5%) as compared to the controls (36.5%).

    Indeed, in healthy fertile women MMP-9 is weakly expressed in the mid-secretory phase (which is the window of implantation) (7).

    By repressing MMP-2 and MMP-9 expression, resveratrol can also have a similar effect on restoring optimal uterine environment and endometrial receptivity thus leading to increased chances for pregnancy. Further, resveratrol has been shown in vitro to promote endometrial receptivity by increasing two proteins E-cadherin and glycodelin thus promoting implantation (8).

    As leaders in the field of Reproductive Immunology, we are taking pride in carefully reviewing any scientific evidences on different molecules showing beneficial effects on women fertility.

    Resveratrol is one of the ingredients included in our Endo-Optimize supplement, the best solution to counteract inflammation and oxidative stress induced-DNA damage.

    It optimizes your egg quality as well as minimizing your symptoms associated with endometriosis and PCOS.

    This all in one pill contains many ingredients enhancing mitochondrial activity (a key component in oocyte development) and reducing inflammation thus allowing optimal microenvironment for the oocyte development and maturation.

    Questions? Call 516.584.8710
    We would be happy to help you take control of your fertility journey and answer any questions you may have.


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