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.

• Authors: Hanyia Naqvi, Ramanaiah Mamillapalli, Graciela Krikun, Hugh S Taylor
• Journal: Reproductive sciences (Thousand Oaks, Calif.) (Reprod Sci) Vol. 23 Issue 2 Pg. 186-91 (Feb 2016) ISSN: 1933-7205 [Electronic] United States
• PMID: 26516123 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author(s) 2015.

Chemical References

• Homeobox A10 Proteins
• Homeodomain Proteins
• Hoxa11 protein, mouse
• Insulin-Like Growth Factor Binding Protein 1
• Kruppel-Like Transcription Factors
• Receptors, Progesterone
• Hoxa10 protein, mouse

Topics

• Animals
• Disease Models, Animal
• Endometriosis (genetics, metabolism, pathology)
• Endometrium (metabolism, pathology)
• Female
• Gene Expression Regulation
• Homeobox A10 Proteins
• Homeodomain Proteins (genetics, metabolism)
• Insulin-Like Growth Factor Binding Protein 1 (genetics, metabolism)
• Kruppel-Like Transcription Factors (genetics, metabolism)
• Mice
• Peritoneal Diseases (genetics, metabolism, pathology)
• Receptors, Progesterone (genetics, metabolism)
• Uterus (metabolism, pathology)