An update on the role of prokineticins in human reproduction-potential therapeutic implications

Abstract

Objective: Prokineticin-1 (PROK1) is a recently described protein with a wide range of functions including tissue specific angiogenesis, modulation of inflammatory responses and regulation of haematopoiesis. PROK1 has been found in the steroidogenic organs like ovary, testis, adrenal and specially placenta and they have been found to have a role in development of the olfactory system and GnRH system. The aim was to update the role of PROK1 and PROK2 in human reproduction since the review was provided by Maldono-Perez (2007) on the potentials of prokineticins in reproduction. Design: A review of international scientific literature by a search of Pubmed and the authors files was done for citation of articles relevant to prokineticins in reproduction, be it its role in ovary, testis, uterus with special emphasis on implantation, normal pregnancy, in labour, pathophysiological states like tubal pregnancy, pcos, various genital tumours, and cases of isolated hypogonadotropic hypogonadism with mutations with PROK2/ PROKR2 and studies detailing functional mechanisms. Results: In the normal cycle, PROK1 has been found to have important roles in implantation, regulating several genes like COX-2, IL-8, IL-11, CTGF related to implantation. Initially murine studies revealed a critical role of PROK2 pathway on olfactory bulb morphogenesis and GnRH secretion which was accidentally discovered and since then several studies on mutations in PROK2/PROKR2 showed that they underlie some case of KS in humans. Although in mouse heterozygote state is not associated with clinical phenotype, most of human mutations are heterozygous. Conclusions: Role of PROK-1 in the process of implantation, with a deeper understanding of the process success rates in IVF and ART can be improved, besides understanding the pathophysiology of tubal pregnancy. Further presence in ovarian follicles of PROK1 can be used to plan a strategy for treating pcos. Development of antagonism of PROK'S may be a helpful strategy in treating preterm labour.

Utilizing the Knowledge of Role of Matrix Matrixmetalloproteinases Along with Tissue Inhibitors of Matrix Metalloproteinasesin Various Gynaecological Disorders with Great Emphasis on Preeclampsia, PCOs Along with Gynaecological Malignancies-A Systematic Review

“…Earlier we have reviewed role of prokineticins in reproduction [128] Su MT, had documented the role of miR-346 and miR-582-3p in controlling EG-VEGF expression and trophoblast invasion via matrix metalloproteinases 2 and 9 [129]. Further earlier we had reviewed the role of epigenetics in Preeclampsia,and recently the role of Extracellular Vesicles (ECV's),in human reproduction and how we can utilize their cargo like miRNA's in treating various metabolic diseases like DM, and similarly might utilize them for targeting miR's along with MMP's in Preeclampsia [130][131][132].…”

Idiopathic Hypogonadotropic Hypogonadism— An Update on the Aetiopathogenesis, Management of IHH in Both Males and Females—An Exhaustive Review

“…Still a lot of controversial issues remain regarding role of PROK signaling as highlighted in ref. [27] regarding absence of PROK receptors on GnRH neurons, mode of inheritance-digenic/oligogenic [43] with presence of PROK2 mutations even in normosmic HH and thus extending the role beyond olfactory bulb development and GnRH neuronal migratrion and absence of any defect in homozygous mutations while most of human presentations being in heterozygous mutations. Although some answers are provided by the link between TSHZ1, which bound to and regulated the expression of gene encoding PROKR2, a GPCR essential for OB development.…”