Transcriptional profiling of endometriosis tissues identifies genes related to organogenesis defects

Endometriosis is a common benign pathology, characterised by the presence of endometrial tissue outside the endometrial cavity with a prevalence of 10-15% in reproductive-aged women. The pathogenesis is not completely understood, and several theories have been proposed to explain the aetiology. Our group has recently described the presence of ectopic endometrium in a consistent number of human female foetuses analysed by autopsy, reinforcing the hypothesis that endometriosis may be generated by defects during the organogenesis of the female reproductive trait. Herein, in order to identify, at molecular level, changes involved in the disease, we compared the transcriptional profiling of ectopic endometrium with the corresponding eutopic one. Statistical analyses lead us to identify some genes specifically deregulated in the ectopic endometrium, that are involved in gonad developmental process or in wound healing process. Among them, we identified BMP4 and GREM1. BMP4 was never associated before to endometriosis and is involved in the mesoderm-Müllerian duct differentiation. GREM1 is needed for the initial step of the ureter growth and perhaps could possibly be involved in Müller ducts differentiation. These molecules might be related to the endometriosis aetiology since we showed that their expression is not related to the menstrual cycle phase both at RNA and at protein levels. These data support the theory that embryological defects could be responsible of the endometriosis generation.