Endometriosis is a common gynecological disease, can cause severe pelvic pain. Studies demonstrated the presence of sensory nerve fibers in endometrium of endometriosis patient. Nevertheless, no information is available on mechanisms of sensory nerve formation in eutopic or ectopic lesions. Since HOX genes have important roles in both reproductive tract and nerve growth, we decided to determine role of them in formation of new nerve fibers in endometriotic lesions.
Materials and methods
Samples obtained from fifteen patients (15 with and 15 without endometriosis) of reproductive age with normal menstrual cycles, where the same patient provided both eutopic and ectopic tissues and control samples were surgically checked for the absence of endometriosis. The expression profile of 84 genes of HOX family related to various aspects of nerve fibers formation (formation of nociceptors, dopaminergic neurons and signal transduction) was investigated using qRT-PCR array.
Our data showed significant over-expression of some genes which are involved in various aspect of development of sensory neurons in the tissue and signal transduction such as genes that involved in relay pain, touch and GABAergic neurons formation (VAX1 , LBX1, LBX2 and PITX2), dopaminergic neurons (EN1 and PITX3), committed to a cutaneous sensory neuron fate (PAX3), chemosensory integration (PHOX2b), promote nerve formation (DRGX, EMX1, PHOX2B and OTP), various aspects of somatic motor neuron (ISL1, 2), neuronal migration (HLX) and touch/mechanosensory neurons (SHOX2) in euotopic and ectopic tissue versus control group. All of these genes have significant differences more than 30-1800 times in fold regulation between groups and P value for each of them is less than 0.001.
Overexpression (up to 1800 times) of some HOX family related genes that play critical roles in sensory, adrenergic and cholinergic neurons formation, lead to aberrant innervations of ectopic and euotopic tissues. So, formation of new plexus of neuron and secretion of many inflammatory mediators released from endometriotic lesions can stimulate sensory nerve fibers to cause pain symptoms.