Transcriptome and DNA methylome analyses reveal underlying mechanisms for the racial disparity in uterine fibroids

Abstract

Uterine fibroids (leiomyomas) affect Black women disproportionately in terms of prevalence, incidence, and severity of symptoms. The causes of this racial disparity are essentially unknown. We hypothesized that myometria of Black women are more susceptible to developing fibroids and examined the transcriptomic and DNA methylation profiles of myometria and fibroids from Black and White women for comparison.Myometrial samples cluster by race in both their transcriptome and DNA methylation profiles, whereas fibroid samples only cluster by race in the latter. More differentially expressed genes (DEGs) were detected in the Black and White myometrial sample comparison than in the fibroid comparison. Leiomyoma gene set expression analysis identified four clusters of DEGs, including a cluster of 24 genes with higher expression in myometrial samples from Black women. One of the DEGs in this group, VWF, was significantly hypomethylated at two CpG probes that are near a putative enhancer site in myometrial samples from Black women and in all fibroids and that correlate with VWF expression levels. These results suggest that the molecular basis for the disparity in fibroid disease between Black and White women could be found in the myometria before fibroid development and not in the fibroids themselves.

The Effect of Race/Ethnicity and MED12 Mutation on the Expression of Long Non-Coding RNAs in Uterine Leiomyoma and Myometrium

“…Our data showed that the comparison of gene expression between Lyo and adjacent Myo is similar to the comparison with non-diseased Myo, although for the upregulated lncRNAs, the magnitude of change was more pronounced for most lncRNAs when comparison was made with non-diseased Myo. This finding, along with the significant differences in expression of several lncRNAs in diseased versus non-diseased Myo, supports the notion that the presence of Lyo in and of itself could potentially affect the expression of lncRNA in the adjacent Myo, as previously suggested [44]. However, due to immense heterogeneity in fibroid tissues and our finding demonstrating a similar pattern of differential expression for most lncRNAs using diseased versus non-diseased Myo, the commonly used practice of comparing gene expression levels in Lyo with adjacent Myo is supported.…”

“…A strength of this study was that comparisons of lncRNA levels were made both with matched Myo from the diseased uteri and with non-diseased Myo in patients not using hormonal medications prior to surgery. A recent study [44] suggested the use of Myo from non-diseased uteri to compare with Lyo is more advantageous than a comparison made with diseased Myo because of potential effects of leiomyomas on the adjacent Myo. Our data showed that the comparison of gene expression between Lyo and adjacent Myo is similar to the comparison with non-diseased Myo, although for the upregulated lncRNAs, the magnitude of change was more pronounced for most lncRNAs when comparison was made with non-diseased Myo.…”

A comparative study on myomectomy and total hysterectomy in the treatment of perimenopausal uterine fibroids

“…Hence, total hysterectomy treatment needs to be combined with bilateral salpingectomy at the same time. This will impact their ovarian function in varying degrees [15]. follicle-stimulating hormone (FSH), luteinising hormone (LH) and estradiol (E2) are all commonly used indicators to evaluate sexual hormones.…”

Psychosocial stress and microRNA expression profiles in myometrial tissue of women undergoing surgical treatment for uterine fibroids

“…These epigenetic changes in myometrial tissues are thus primed to a pro-fibroid phenotype that may readily respond to adverse environmental conditions that contribute to fibroid development. Recent evidence found epigenetic mechanisms may underlie the racial differences in fibroid disparities and primed myometrial stem cells are expanded in Black women [ 48 , 49 ]. Taken together, it is plausible that the disproportionate prevalence of fibroids in underserved communities, including Black women, may arise from epigenetic priming of progenitor myometrial cells and otherwise healthy myometrium to a pro-fibroid state early during development that is amenable to the effects of environmental exposures ( i.e ., psychosocial stressors), that, when accumulating over time, may readily transition to fibroids.…”