Potential roles of the prokineticins in reproduction

Abstract

Prokineticins are multifunctional secreted proteins that were originally identified as regulators of intestinal contraction but subsequently shown to affect vascular function, hyperalgesia, spermatogenesis, neuronal survival, circadian rhythm, nociception, feeding behaviour, immune responses, haematopoiesis and the development of the olfactory and gonadotropin-releasing hormone systems. Their role in the reproductive tract is still not fully elucidated, although they are reputed to increase microvascular permeability. Expression of prokineticins and their receptors has been reported in the ovary, uterus, placenta, testis and prostate. Their expression has also been reported in various pathologies of the reproductive tract, and future studies will highlight whether inhibition of prokineticin function in these pathologies would be a useful therapeutic target.

Role of EG-VEGF in Human Placentation: Physiological and Pathological Implications

“…Prokineticins were originally identified as regulators of intestinal contraction but subsequently shown to affect vascular function, neuronal survival, nociception, immune responses, and gonadotropin releasing hormone systems (Battersby et al, 2004, Dorsch et al, 2005, LeCouter et al, 2003, Maldonado-Perez et al, 2007. Quickly after their discovery, the members of this family showed differential specificities of expression and preferential sites of actions.…”

“…While Bv8/PROK2 was associated to the neuronal system, EG-VEGF was more associated to the reproductive tract. EG-VEGF has been well studied in the ovary, uterus, testis, prostate and placenta (Battersby et al, 2004, Brouillet et al, 2010, Dorsch et al, 2005, Fraser et al, 2005,Hoffmann et al, 2007,2006, Hoffmann et al, 2009, LeCouter et al, 2001, LeCouter et al, 2003, Maldonado-Perez et al, 2007, Pasquali et al, 2006.…”

“…However, insightful work on EG-VEGF throughout pregnancy came from our group with a focus on early pregnancy and from the group of Dr Jabbour with more focus on the decidual unit, at the term of human gestation (Catalano et al, 2010, Maldonado-Perez et al, 2007.…”

“…The group of Jabbour (Cook et al, 2010,Evans et al, 2008, Maldonado-Perez et al, 2007 has reported the localization of EG-VEGF and that of its receptors in term placenta and decidua; studied its signaling pathways, and demonstrated the effect of EG-VEGF on the expression of two inflammatory and vascular mediators, the cyclooxygenase (COX)-2 and IL-8 in thirdtrimester placentas. IL-8 is a potent neutrophil chemoattractant and angiogenic factor, promoting endothelial cell chemotaxis (Winkler, 2003), whereas COX-2 is the inducible isoform of the enzyme involved in the synthesis of prostaglandins from arachidonic acid.…”

Regulation of endometrial vascular remodelling: role of the vascular endothelial growth factor family and the angiopoietin–TIE signalling system

“…The current review will focus on three members of the VEGF family (VEGFA, VEGFC, VEGFD) and their receptors, and the ANG-TIE signalling system. Although not addressed in this review, the importance of other regulators, including (but not limited to) fibroblast growth factor, thrombospondin, relaxin, adrenomedullin, the prostaglandins, the prokineticins and the matrix metalloproteinases, cannot be overstated (see Nikitenko et al 2000, Jabbour et al 2006, Maldonado-Perez et al 2007, Parry & Vodstrcil 2007, Chennazhi & Nayak 2009) and references therein for additional information). Considerable effort is still required to understand the complex interactions between these regulators in endometrial vascular remodelling.…”