TITLE:
An update on the role of prokineticins in human reproduction-potential therapeutic implications
AUTHORS:
Kulvinder Kochar Kaur, Gautam Allahbadia, Mandeep Singh
KEYWORDS:
Prokineticin 1; Prokineticin Receptor 2; Kallmanns Syndrome; Implantation; GnRH Development
JOURNAL NAME:
Open Journal of Genetics,
Vol.3 No.3,
August
28,
2013
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 inhuman
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.