Oxytocin receptor gene expression in patients with uterine fibroids

BACKGROUND: Uterine fibroids are hormone-dependent tumors in which the local microenvironment and the fibroid pseudocapsule play an important role. The oxytocin receptor, encoded by the OTR gene, may contribute to the regulation of contractile activity, vascularization, and tissue remodeling; however, its expression in the pseudocapsule remains insufficiently studied. AIM: The aim of this study was to assess oxytocin receptor expression in fibroid nodules, the pseudocapsule, and intact myometrium in women with uterine fibroids. METHODS: This single-center case series included patients of reproductive-age with isolated uterine fibroids who underwent laparoscopic myomectomy. OTR mRNA expression in the dominant fibroid, its pseudocapsule, and the myometrium was determined using real-time polymerase chain reaction. The nodules were typed based on the presence of a somatic MED12 gene mutation and HMGA2 gene overexpression. Statistical analysis was performed using nonparametric tests (p 0.05). RESULTS: The study included 27 patients. OTR gene expression was increased in the myometrium and pseudocapsule compared to the fibroid nodules. In all examined nodules, the OTR gene was expressed at a low level or was not detected. No association was found between fibroid size and OTR gene expression in either the myometrium or the pseudocapsule. Comparison of patients with a solitary fibroid versus multiple fibroids revealed no differences in OTR gene expression. Myometrial OTR gene overexpression was characteristic of fibroid nodules harboring a MED12 gene mutation, whereas in the absence of such mutations, OTR gene expression in the myometrium remained low or undetectable. In nodules with HMGA2 gene overexpression, OTR mRNA levels in the myometrium also remained low. No differences in the pseudocapsule OTR gene expression were found between patient subgroups with different driver types. In the pseudocapsule, OTR gene expression levels were higher in the luteal phase than in the follicular phase of the menstrual cycle. CONCLUSION: The pseudocapsule and adjacent myometrium in patients with uterine fibroids are characterized by overexpression of the OTR gene, while OTR gene expression remains low in the fibroid tissue. The identified associations between OTR gene expression levels and MED12 status confirm a compartment-specific impact of driver genetic events on the oxytocin system. Increased OTR gene expression in the pseudocapsule indicates its specific hormonal sensitivity and supports the concept of the pseudocapsule as an independent structural and functional unit that may contribute to the regulation of growth, vascularization, and repair in uterine fibroids.