Dietary Fish Oil Supplementation Inhibits Formation of Endometriosis-Associated Adhesions in a Chimeric Mouse Model

Capsule:
In an established model of spontaneous adhesive disease associatedwith experimental human endometriosis in nude mice, development of adhesions was significantly reduced in animals provided with an antiinflammatory diet containing fish oil.

Authors:
Jennifer L. Herington, Ph.D., Dana R. Glore, B.S., John A. Lucas, M.D., Kevin G. Osteen, Ph.D., Kaylon L. Bruner-Tran, Ph.D.

Volume 99, Issue 2, Pages 543-550.e1, February 2013

Abstract:

Objective:
To examine whether dietary fish oil supplementation reduces development of spontaneous endometriosis-associated adhesions using an established model.

Design:
Laboratory-based study.

Setting:
Medical center research laboratory.

Patients/Animals:
Disease-free women of reproductive age and nude mice.

Interventions:
Women were not provided any intervention. Mice were randomized to receive fish oil supplementation or control diet.

Main Outcome Measures:
Experimental endometriosis was established in mice via injection of human endometrial tissue within 16 hrs of ovariectomy. Mice were provided standard or Menhaden fish oil supplemented diets for at least two weeks prior to initiation of experimental endometriosis and until euthanasia one week later. At necropsy, mice were examined for the presence and extent of adhesions and endometriotic-like lesions. Tissues were excised and morphologically characterized.

Results:
Adhesions/lesions were reduced in mice provided dietary fish oil compared to control animals. Leukocytes were more numerous within the adhesions/lesions of the mice maintained on the standard diet compared to animals provided fish oil. As indicated by staining intensity, collagen deposition was greater at adhesion sites within control mice compared to fish oil-supplemented animals.

Conclusion:
Wound-healing associated with surgery created an inflammatory peritoneal microenvironment that promoted the development of both experimental endometriosis and adhesions in a murine model. Targeting excessive inflammation with fish oil may be an effective adjuvant therapy to reduce the development of post-surgical adhesions related to endometriosis.

  • Congratulations to the authors on this nice paper.
    These anti-inflammatory effects may well be due to the anti-inflammatory eicosanoids such as Resolvins, known to be metabolised from fish oil. Large-scale Italian studies have already shown fish oils to be protective in the context of heart disease. As a comment, to Dr. Gomez’s questions, transgenic mice would be necessary to address such questions in vivo, dissecting out the relative contributions of different cell types and there is abundant evidence that these anti-inflammatory, pro-resolution mediators act on various immune cells. The role of relevant receptors should also be taken into account and I would be interested to know if the estrogen receptor system is impacted.
    I am glad to see the areas of nutrition, metabolism and reproduction converging, there is much research to be done to delineate such links.

  • Raul Gomez, PhD, IUIVI

    Congratulations to the authors for this paper.
    I have found it really thrilling. Besides, taking into account that
    endometriosis is a very common disease and that their presence causes
    reproductive and gynecologic problems, the idea that the gravity of the disease
    could be palliated or mitigated with a little change in the daily diet is
    certainly interesting.

    I would like to know the authors opinion on a couple of issues

    a) author points to the important relationship between the inflammatory process and the risk for developing endometriosis. As the animals used in this work are
    immunocompromised mice, I wonder whether the lack of lymphocytes T, which are
    involved in the anti-inflammatory response, could have an impact in the results
    obtained. I Know these animals have lymphocytes B and NK cells, but as I am not
    a specialist in immune system I would like to know the opinion of the authors
    about the potential contribution of each of these cell population on the
    results obtained

    b) I have a, let´s say methodological curiosity, we have some experience with heterologous animal models of endometriosis in which we do fix the endometrial xenografts in the intraperitoneal cavity employing a tissue adhesive. After several weeks
    when we sacrifice the animals and try to retrieve the implants, sometimes we
    find difficult to detect them, well the fact is that we lose some of
    them . So, taking into account that you inject the fragments, and you do not
    fix them in one known region or area, I am intrigued to know in how you exactly manage
    to detect all the implants, with no loss.

    Once more, congratulations to the authors for
    this terrific work.

    • Dr Gomez another poster has posted a reply referencing your comments on this interesting new study–it was posted as a separate comment in the thread

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