Abstract
Endometriosis is a prevalent gynecological disease, with limited known etiology and more researches are required to identify its etiology. In this manner, there is no evidence for expression and function of 3´HOX genes in 4 clusters in the limb and pelvic organs such as the uterus and its disorders (Genes in the HOXA-D clusters are subdivided into 13 paralogous groups). This study designed to investigate the expression profile of 5 paralogous (1-5) in four clusters of HOX genes (A, B, C, and D) in ectopic and eutopic tissues of women with endometriosis compared to the normal endometrium. Samples were obtained from thirty patients (15 with and 15 without endometriosis) of reproductive age with normal menstrual cycles. The same patient provided both eutopic and ectopic tissues and control women were laparoscopically checked for the absence of endometriosis. The expression profile of these HOX genes was investigated by quantitative real-time polymerase chain reaction technique. We observed significant up-regulation of some members of HOXC and D clusters (HOXD1, HOXD3, HOXC4 and HOXC5) in ectopic and eutopic tissues vs. control. Also, our data showed significant down-regulation of all of HOXA and HOXB paralogous except HOXA1 in ectopic tissues versus control. Our data showed specific cluster dependent modulation of the HOX genes expression in endometriosis (over-expression of some HOX genes in cluster C and D and down-regulation of HOX genes in cluster A and B) in ectopic and eutopic tissues compare to control group. Therefore, it is possible that change of expression level of these genes in endometrium plays a role in the pathogenesis of endometriosis.
Highlights
Endometriosis is a gynecological disease, demonstrate by the presence of endometrial glands and stroma located in ectopic sites such as pelvic, peritoneum, ovaries, and rectovaginal septum
Expression of 3 ́paralogus genes in HOXA (1, 2, 3, 4, and 5), HOXB (1, 2, 3, 4, and 5), HOXC (4, and 5), and HOXD (1, 3, and 4) clusters were quantitatively evaluated in normal endometrium of healthy women, compare to eutopic and ectopic tissue of endometriosis patients
HOXA3, HOXA4, and HOXA5 showed significant down-regulation in ectopic group compare to the control group (p=0.0002, 0.0049, and 0.0032 respectively), there was significant down-regulation in eutopic group compare to the control group (p=0.009, 0.0052, and 0.0033), HOXA2 was significantly down-regulated in ectopic group compare to the eutopic and control group (p=0.0045, and 0.0050 respectively), there was no significant difference in mRNA expression of HOXA1 between all groups
Summary
Endometriosis is a gynecological disease, demonstrate by the presence of endometrial glands and stroma located in ectopic sites such as pelvic, peritoneum, ovaries, and rectovaginal septum. The most recognizable signs of the disease is pain such as chronic dysmenorrhea, intermenstrual abdominal and pelvic pain and back pain [1]. Endometriosis is considered as a complicated disorder and despite its high frequency; the etiology of the disease is not well understood. Recent studies have suggested that abnormalities in the regulation of specific genes are involved in the incidence of endometriosis [4,5,6,7]. In women with particular genetic backgrounds, specific networks of genes are involved in endometrial tissue formation [8]. Specification of various parts of body along the axis, from the branchial area through to the tail, is controlled by HOX genes [9]
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