Genome-wide DNA methylation analysis predicts an epigenetic switch for GATA factor expression in endometriosis.

Endometriosis is a gynecological disease defined by the extrauterine growth of endometrial-like cells that cause chronic pain and infertility. The disease is limited to primates that exhibit spontaneous decidualization, and diseased cells are characterized by significant defects in the steroid-dependent genetic pathways that typify this process. Altered DNA methylation may underlie these defects, but few regions with differential methylation have been implicated in the disease. We mapped genome-wide differences in DNA methylation between healthy human endometrial and endometriotic stromal cells and correlated this with gene expression using an interaction analysis strategy. We identified 42,248 differentially methylated CpGs in endometriosis compared to healthy cells. These extensive differences were not unidirectional, but were focused intragenically and at sites distal to classic CpG islands where methylation status was typically negatively correlated with gene expression. Significant differences in methylation were mapped to 403 genes, which included a disproportionally large number of transcription factors. Furthermore, many of these genes are implicated in the pathology of endometriosis and decidualization. Our results tremendously improve the scope and resolution of differential methylation affecting the HOX gene clusters, nuclear receptor genes, and intriguingly the GATA family of transcription factors. Functional analysis of the GATA family revealed that GATA2 regulates key genes necessary for the hormone-driven differentiation of healthy stromal cells, but is hypermethylated and repressed in endometriotic cells. GATA6, which is hypomethylated and abundant in endometriotic cells, potently blocked hormone sensitivity, repressed GATA2, and induced markers of endometriosis when expressed in healthy endometrial cells. The unique epigenetic fingerprint in endometriosis suggests DNA methylation is an integral component of the disease, and identifies a novel role for the GATA family as key regulators of uterine physiology-aberrant DNA methylation in endometriotic cells correlates with a shift in GATA isoform expression that facilitates progesterone resistance and disease progression.

Lidocaine spray in addition to paracervical block reduces pain during first-trimester surgical abortion: a placebo-controlled clinical trial.

BACKGROUND: A variety of anesthetic and analgesic techniques have been used for uterine aspiration, and most clinicians use a paracervical block with or without additional analgesia. We intended to evaluate whether the addition of 10% lidocaine spray to a paracervical block decreases pain during cervical dilation and uterine aspiration. STUDY DESIGN: Seventy-seven patients were divided into two groups: paracervical blocks (PCB) (n = 30) and PCB plus 10% lidocaine spray (n = 47). Anticipated and overall perceived pain scores were measured with a standard Visual Analog Scale (VAS). RESULTS: Anticipated pain VAS scores of two groups were similar, however overall perceived pain VAS scores demonstrated a significant difference. PCB with Lidocaine only group had 6.56 ± 1.43 cm mean VAS score, whereas lidocaine plus lidocaine spray group had 2.35 ± 1.39 cm, the difference being statistically significant (p < .01). CONCLUSION: We found that 10% lidocaine spray safely decreases perceived pain during first-trimester surgical abortion, when used in addition to PCB with lidocaine HCl.