SLIT3 gene expression by 1,25(OH)?D? in an endometriosis stromal cell line

Endometriosis is a common and sometimes severe health disorder in women. This disease is characterized by the invasion of endometrial cells into other areas of the body such as the peritoneum, ovaries, bladder, and more. Symptoms of endometriosis include but are not limited to severe dysmenorrhea, deep dyspareunia, chronic pelvic pain, ovulation pain, menstrual pain, irregular flow, premenstrual spotting, infertility, chronic fatigue, or any combination of the list. Vitamin D3 is a secosteroid hormone that plays an important role not only in bone development and maintenance but also in the cell proliferation, differentiation, and apoptosis. Calcitriol (1,25(OH)?D?) is the biologically active metabolite of vitamin D3. Several studies have shown that a vitamin D system is active in certain tissues of the female reproductive system. In this study, we examine the effects of 1,25(OH)?D? on gene expression in endometrial tissue obtained from patients with endometriosis. Stromal cell lines derived endometriosis patients were treated with 1,25(OH)?D?. Using RNA-Seq, differential gene expression was compared between treated and untreated groups. 1627 genes were at least two-fold differentially expressed. SLIT3, part of the axonal guidance signaling pathway and one of the most down-regulated genes, plays an important role in inhibiting cell migration and invasion and stimulating neuroangiogenesis. Using quantitative RT-PCR, the more invasive endometriosis lesions were determined to have higher SLIT3 expression compared to lesions in the uterine cavity. These results provide evidence for SLIT3 as a gene target in endometriosis and vitamin D3 as a treatment for this disease.