New Potential Therapeutic Strategy for Endometriosis Based on Retinoic Acid

New Potential Therapeutic Strategy for Endometriosis Based on Retinoic Acid

A new study recently published in the Journal of Ovarian Research revealed that retinoic acid has therapeutic potential for the treatment of endometriosis. The study is entitled “Retinoic acid has the potential to suppress endometriosis development” and was developed by researchers at Yamaguchi University Graduate School of Medicine in Japan.

Endometriosis is a nonmalignant gynecological disorder in which the endometrium (tissue that normally lines the inside of the uterus) grows outside the uterus, usually in the abdominal cavity, where it can form lesions and cysts, scarring organs like the ovaries, bladder and rectum. The tissue, although displaced, still continues to act normally as inside the uterus, so it thickens, breaks down and bleeds with each menstrual cycle. Endometriosis can be a painful disorder, causing chronic inflammation in the pelvic cavity and very heavy periods. It is estimated that up to 10% of women in reproductive age suffer from this condition and it can cause infertility in up to 50% of the cases. The exact causes of this disorder are unknown.

Retinoic acid is a metabolite of vitamin A (retinol), important for growth and development in animals, including humans. All-trans retinoic acid (ATRA) is the active form of retinoic acid. Retinoic acid also has immunomodulatory and anti-inflammatory properties, and is thought to be necessary for normal endometrial cell differentiation and functions. Abnormal retinoid metabolism has been suggested to be involved with the pathophysiology of endometriosis.

In the study, researchers assessed the potential use of ATRA as a therapy for endometriosis. The team analyzed the transcriptome (set of RNA molecules) and the levels of estradiol (the primary female sex hormone and key modulator of endometriosis development) in cultured endometriotic cells and tissues isolated from ovarian endometrial cysts.

The team found that the supplementation of ATRA for four days in an endometriotic cell culture induced the up-regulation of 49 genes and down-regulation of 4 genes. Among the upregulated genes, many were associated with the suppression of cell proliferation. One of the downregulated genes by ATRA treatment was the 17-beta-dehydrogenase 2 (HSD17B2), which is responsible for the conversion of estradiol into estrone in a dose-dependent manner. Estrone is a known carcinogen for human females. Researchers also found that estradiol production in the ovarian endometrial cyst tissues was blocked by ATRA treatment.

The research team concluded that retinoic acid has a therapeutic potential for the treatment of endometriosis. Further studies are, however, required to confirm this possible therapeutic strategy.

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