Taylor, R. N., Kane, M. A., & Sidell, N. (2015). Pathogenesis of Endometriosis: Roles of Retinoids and Inflammatory Pathways. Seminars in reproductive medicine, 33(4), 246-56. https://doi.org/10.1055/s-0035-1554920
Taylor RN, Kane MA, Sidell N. Pathogenesis of Endometriosis: Roles of Retinoids and Inflammatory Pathways. Seminars in reproductive medicine. 2015;33(4):246-56. doi:10.1055/s-0035-1554920
Taylor, R. N., et al. "Pathogenesis of Endometriosis: Roles of Retinoids and Inflammatory Pathways." Seminars in reproductive medicine, vol. 33, no. 4, 2015, pp. 246-56.
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Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility (Drs. Peterson and Taylor), University of Utah, Salt Lake City, Utah.03r0ha626
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RRM Academy Synopsis
Endometriosis lesions make less retinoic acid, a vitamin A product
A 2015 review by three researchers reports that endometriosis lesions made less retinoic acid than the uterine lining of the same women in matched samples. The authors draw on lab, animal, and some human studies. They predict that retinoid supplementation might offer a new long-term treatment option.
Key Findings
In tissue from women with endometriosis, lesions made less retinoic acid than the uterine lining of the same woman, with reduced cellular retinol-binding protein type 1 (RBP1).
In an immunocompetent mouse model, retinoic acid treatment limited how well ectopic implants took hold and grew in the peritoneum, and lowered IL-6 and MCP-1 in peritoneal fluid.
In a rat model, retinoic acid, bevacizumab and sorafenib each significantly shrank implants. Retinoic acid gave the best results without affecting angiogenic parameters.
Women with endometriosis having IVF had significantly lower mean retinoic acid, but not retinol, in plasma and follicular fluid than infertile women without it. Levels were within the reported normal concentration range.
Interpretation
The paper is a narrative review by researchers whose laboratories study retinoids in endometriosis. Most evidence comes from cell cultures, mouse and rat models, and tissue samples. The human data include one comparison of retinoid levels in women having IVF. The authors state that the cause and effect link between low retinoic acid and endometriosis is unknown. The authors call for developing add-on medicines built on these ideas.
RRM Context
Restorative reproductive medicine looks for causes of disease. This review adds vitamin A biology to that search. The authors call laparoscopic excision a mainstay of treatment for pain and infertility. They describe retinoid therapy as an adjuvant or alternative to excision, and they note that medical therapy is moving beyond hormone suppression toward inflammation and oxidative stress.
Our editorial summary of this paper, not the article's abstract.
Abstract
Endometriosis is a nonmalignant, but potentially metastatic, gynecological condition manifested by the extrauterine growth of inflammatory endometrial implants. Ten percent of reproductive-age women are affected and commonly suffer pelvic pain and/or infertility. The theories of endometriosis histogenesis remain controversial, but retrograde menstruation and metaplasia each infer mechanisms that explain the immune cell responses observed around the ectopic lesions. Recent findings from our laboratories and others suggest that retinoic acid metabolism and action are fundamentally flawed in endometriotic tissues and even generically in women with endometriosis. The focus of our ongoing research is to develop medical therapies as adjuvants or alternatives to the surgical excision of these lesions. On the basis of concepts put forward in this review, we predict that the pharmacological actions and anticipated low side-effect profiles of retinoid supplementation might provide a new treatment option for the long-term management of this chronic and debilitating gynecological disease.
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