الفهرس 
AcknowledgmentsOnly 14 pages are availabe for public view
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Abstract
RFamides are a -#103;-#114;-#111;-#117;-#112; of peptides that are -#99;-#104;-#97;-#114;acterized by the possession of arginine, phenylalanine, and amine -#103;-#114;-#111;-#117;-#112; motif at their carboxyl-terminus extremities. In vertebrates, there are only 5 RF-amide peptide subfamilies: (i) neuropeptide FF (NPFF) group; (ii) prolactin-releasing peptide (PrRP) group; (iii) gonadotropin-inhibitory hormone (GnIH) group, including mammalian orthologues RFamide-related peptides (RFRP-1 and RFRP-3); (iv) kisspeptin group, which is also known as metastin; and (v) 26RFa/QRFP group. These peptides serve a wide range of biological processes in vertebrates, e.g., reproductive behavior, and in control of the reproductive axis, in pain modulation, and in control of feeding. However, more research is still needed to fully understand the functions of different RFamides. br In reproduction, 4 out of these 5 subfamilies have been studied. For example, kisspeptin, which has antimetastatic properties in cancer, was found to be acting as a regulator of the hypothalamic pituitary gonadal axis upstream of GnRH. It also serves as a mediator of the sex steroid feedback effect on the hypothalamus and is essential in orchestrating the maturation of the HPO axis at the time of puberty. Furthermore, kisspeptin was found to be peripherally expressed in various tissues, including the placenta, the ovaries, and the lining of the upper genital tract, -#119;-#104;-#101;-#114;-#101; it regulates placentation, steroidogenesis, and ovulation and implantation, RFRP-3 is suppressor of the hypothalamic pituitary ovarian access centrally, while peripherally it suppresses steroidogenesis in the ovaries. PrRP is a possible mediator of the steroid-induced preovulatory LH surge, and, to a lesser extent, it could be implicated in stimulating prolactin release. Finally, 26RFa and QRFP-43 peptides were found to induce GnRH mediated FSH and LH release -#102;-#114;-#111;-#109; the pituitary. br The aim of this thesis was to explore the role of 2 RFamide peptides in 4 distinctive area concerning reproduction. br 1- As described in my thesis, I studied the effect of kisspeptin being used as a trigger for ovulation on the expression of 2 important endometrial implantation markers (LIF and ITG αVβ3) in mice. br Compared with hCG or placebo, kisspeptin trigger was found to be associated with higher expression of LIF, and, to a lesser extent, ITG αVβ3 in the mouse endometrium, using the immunohistochemistry method. The results indicate the importance of kisspeptin in implantation, even as early as the time of ovulation trigger. br 2- In this thesis, I used the immunohistochemistry method to study the expression of kisspeptin peptide and its receptor in ectopic and eutopic endometrial tissues -#102;-#114;-#111;-#109; women with or without endometriosis. The results of this study showed a differential pattern of expression of kisspeptin, and, to a lesser extent, kisspeptin receptor in these tissues. br Kisspeptin was expressed at a higher level in the eutopic endometrium of women in the control groups than in women with endometriosis. Kisspeptin expression was also higher in the less invasive phenotypes of the disease (SUP) than in the more invasive types (DIE and OMA). These findings suggest a possible role of kisspeptin as an antimetastatic peptide in the pathogenesis of endometriosis. br 3- As continuation to the second experiment, I tried to examine the direct effect of kisspeptin treatment in in vitro primary culture of endometriotic cells, on the migration and invasion capabilities of the cells, using a transwell migration and transwell invasion assay. br As discussed in my thesis, neither treatment of either kisspeptin or its antagonist separately or in combination affected cell migration or invasion. The results suggest that kisspeptin probably does not have the same antimetastatic effect on endometrial stromal cells shown in other cell types such as trophoblasts or cancer cells. However, the possibility of deficient kisspeptin receptor expression in these cells and potential technical errors can’t be excluded. br 4- In this thesis, using immunohistochemistry, I showed for the first time positive immunoreactivity of RFRP-3 in the endometrium and in the endosalpynx. This suggests a possible role of this RFamide in the regulation of reproductive functions at that level. These data suggest a direction for future studies, examining these possible roles of the peptide. br In conclusion, this thesis provides a comprehensive overview of the multiple roles of RFamides in reproduction. In this thesis, I was able to provide new data regarding the function of this -#103;-#114;-#111;-#117;-#112; of peptides both in health and disease.