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. 2013 Feb;99(2):543-50.
doi: 10.1016/j.fertnstert.2012.10.007. Epub 2012 Oct 25.

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

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

Jennifer L Herington et al. Fertil Steril. .
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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. PATIENT(S)/ANIMAL(S): Disease-free women of reproductive age and nude mice.

Intervention(s): Women were not provided any intervention. Mice were randomized to receive fish oil supplementation or control diet.

Main outcome measure(s): Experimental endometriosis was established in mice via injection of human endometrial tissue within 16 hours of ovariectomy. Mice were provided standard or menhaden fish oil-supplemented diets for ≥ 2 weeks before initiation of experimental endometriosis and until killing them 1 week later. At necropsy, mice were examined for the presence and extent of adhesions and endometriotic-like lesions. Tissues were excised and morphologically characterized.

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

Conclusion(s): 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 postsurgical adhesions related to endometriosis.

Figures

FIGURE 1
FIGURE 1
Gross morphology of lesions (arrows) and adhesions (arrowheads) in (A, B) control mice and mice maintained on the (C, D) 10% or (E, F) 5% fish oil diet. Lesions in control mice were significantly larger than those observed in supplemented mice, as illustrated by the large cyst attached to both the spleen and bowel (A) compared with the small nodular lesions observed in a 10% fish oil–supplemented mouse (C) or a 5% fish oil–supplemented mouse (E). Adhesions in control mice were frequently extensive, as shown in (B), in which the uterus is entirely adhered to the posterior peritoneum. In contrast, adhesions present in the 10% fish oil–supplemented group were less extensive, and typically involved the site of the surgical injury, as shown in (D), in which the tip of the left uterine horn is adhered to the kidney. In (F), a thin, filmy adhesion in a 5% fish oil–supplemented mouse is shown attaching the posterior peritoneum to the left uterine horn. Original magnification ×15. Herington. Fish oil inhibition of adhesions. Fertil Steril 2013.
FIGURE 2
FIGURE 2
Masson trichrome staining (A–C) or phosphotungstic acid hematoxylin staining (PTAH; D–F) of adhesions/lesions removed from control (A, D) or mice provided 10% (B, E) or 5% (E, F) fish oil–supplemented diet. Masson trichrome staining results in red-blue cell nuclei, red cytoplasm, and bright blue collagen. Notably, the intensity of the blue stain has been shown to correlate with the extent of collagen present (29). Within tissues obtained from fish oil–supplemented mice, the reduced amount and intensity of blue staining suggests that the amount of collagen is also reduced (B, C). PTAH staining of near sister sections was conducted to assess the presence of fibrin (which appears as a dark blue stain) and was similar in all groups (D–F). The asterisks denote areas containing endometrial glands and stroma, indicative of endometriotic-like lesions, and arrowheads mark sites of abnormal tissue attachment (adhesion). Photomicrographs are representative results of multiple tissues from at least four mice per group. Original magnification ×100. Herington. Fish oil inhibition of adhesions. Fertil Steril 2013.
FIGURE 3
FIGURE 3
Immunolocalization of leukocytes with the use of an antibody directed at CD45 (leukocyte common antigen), which results in brown staining of T and B lymphocytes, granulocytes, monocytes, and macrophages. These leukocytes are abundant in adhesions/lesions obtained from control mice (A, B), but are less frequently observed in mice provided 10% (C, D) or 5% (E, F) fish oil–supplemented diet. Original magnifications ×200 (A, C, E) and ×1000 (B, D, F). Herington. Fish oil inhibition of adhesions. Fertil Steril 2013.

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