Endometriosis Located Proximal to or Remote From the Uterus Differentially Affects Uterine Gene Expression

Abstract

The mechanisms that lead to the altered uterine gene expression in women with endometriosis are poorly understood. Are these changes in gene expression mediated by proximity to endometriotic lesions or is endometriosis a systemic disease where the effect is independent of proximity to the uterus? To answer this question, we created endometriosis in a murine model either in the peritoneal cavity (proximal) or at a subcutaneous remote site (distal). The expression of several genes that are involved in endometrial receptivity (homeobox A10 [Hoxa10], homeobox A11 [Hoxa11], insulin-like growth factor binding protein 1 [Igfbp1], Kruppel-like factor 9 [Klf9], and progesterone receptor [Pgr]) was measured in the eutopic endometrium of mice transplanted with either proximal or distal endometriosis lesions. Decreased expression of Hoxa10, Igfbp1, Klf9, and total Pgr genes was observed in the eutopic endometrium of mice with peritoneal endometriosis. In the mice with distal lesions, overall expression of these genes was not as severely affected, however, Igfbp1 expression was similarly decreased and the effect on Pgr was more pronounced. Endometriosis does have a systemic effect that varies with distance to the end organ. However, even remote disease selectively and profoundly alters the expression of genes such as Pgr. This is the first controlled experiment demonstrating that endometriosis is not simply a local peritoneal disease. Selective alteration of genes critical for endometrial receptivity and endometriosis propagation may be systemic. Similarly, systemic effects of endometriosis on other organs may also be responsible for the widespread manifestations of the disease.

Aberrant Endometrial DNA Methylome and Associated Gene Expression in Women with Endometriosis

“…Our platform has one probe for HOXA10 at +1461, a different location, and shows intermediate methylation in controls and disease, and no differential methylation, thus accounting for the observed differences. Naqvi et al [49] used the Illumina platform and reported on 10 of 120 genes differentially methylated, and none of these 10 genes was in common with our data, potentially because of the use of samples from individuals with different severities of disease and/or different cycle phases, or, as they recently found, the distance of disease from the uterus [50]. Saare et al [33], as mentioned above, have shown similar genome-wide profiles between eutopic endometrium of disease and nondisease as those reported herein.…”

Association of vitamin D intake and serum levels with fertility: results from the Lifestyle and Fertility Study

“…Subjects were participants in the Lifestyle and Fertility Study (ISIS Study), a prospective cohort study of healthy, nulliparous couples with no known infertility conditions, who were planning their first pregnancy (37). The overall objective of the study was to examine the association between antioxidant status and pregnancy.…”

Overexpression of microRNA‐542‐3p attenuates the differentiating capacity of endometriotic stromal cells

“…Aberrant miRNA expression is a feature of many pathological conditions, including cancer, viral infections, metabolic diseases, and neurological disorders 8. In addition, there is growing evidence that miRNAs contribute to the pathogenesis of endometriosis by regulating abnormal cell differentiation, invasion, and inflammation 9, 10, 11…”