Despite the prevalence of uterine fibroids (Fs), few studies have investigated the links between clinical features and the cellular or molecular mechanisms that drive F growth and development. Such knowledge will ultimately help to differentiate symptomatic from asymptomatic Fs and could result in the development of more effective and individualized treatments. The aim of this study was to investigate the relationship between ultrasound appearance, blood flow, and angiogenic gene expression in F, perifibroid (PM), and distant myometrial (DM) tissues. We hypothesized that angiogenic gene expression would be increased in tissues and participants that showed increased blood flow by Doppler ultrasound. The study was performed using Doppler ultrasound to measure blood flow prior to hysterectomy, with subsequent tissue samples from the F, PM, and DM being investigated for angiogenic gene expression. Overall, PM blood flow (measured as peak systolic velocity [PSV]) was higher than F blood flow, although significant heterogeneity was seen in vascularity and blood flow between different Fs and their surrounding myometrium. We did not find any correlation between PSV and any other clinical or molecular parameter in this study. We identified 19 angiogenesis pathway-related genes with significant differences in expression between F and DM, and 2 genes, matrix metalloproteinase 9 (MMP9) and Neuropilin 2 (NRP2), that were significantly different between F and PM. These results are consistent with subtle differences between PM and DM. Understanding the differences between symptomatic versus asymptomatic Fs may eventually lead to more effective treatments that directly target the source of heavy menstrual bleeding.

Understanding of the mechanisms that cause fibroid associated heavy menstrual bleeding (HMB) is limited. Despite many fibroids having a highly vascular peri-fibroid myometrial (PFM) zone, angiogenic gene expression in this area has never been investigated. The aim of this study was to correlate clinical symptoms, ultrasound appearances and tissue gene expression profiles in women scheduled for hysterectomy due to symptomatic fibroids. We hypothesised that fibroid heterogeneity, colour flow and spectral Doppler resistive indices would correlate with differences in gene expression profiles. It was thought and that increased peri-fibroid gene expression of key angiogenic genes would correlate with increased peri-fibroid vascularity. N = 6 patients underwent B-mode, colour and spectral Doppler ultrasound assessment. Following hysterectomy tissue samples collected from three areas – fibroid, PFM and distant myometrium (DM) were analysed using quantitative RT-PCR and a customised angiogenesis PCR array. A higher mean peak systolic velocity (PSV) in the PFM region when compared to mean PSV within the fibroid (P < 0.001) was seen. Differences in angiogenic gene expression were consistent with the heterogeneity of the clinical data collected. One fibroid sample showed dissimilar gene expression to all other fibroids; at ultrasound and sample collection significant degenerative features were observed. Fibroid heterogeneity within a single uterus was also demonstrated, with two fibroids from the one uterus having significantly dissimilar gene profiles and ultrasound appearances. No differences in gene expression were found between PFM and DM. Despite this, gene interaction maps showed different interaction of genes between fibroid and PFM regions compared to genes between the fibroid and the DM. These are the first molecular data demonstrating that the PFM region may be functionally distinct from distant myometrium.