Prokineticin 1 is a new biomarker of human oocyte competence: expression and hormonal regulation throughout late folliculogenesis

Abstract

Context Prokineticin 1 (PROK1) quantification in global follicular fluid (FF) has been recently reported as a predictive biomarker of in vitro fertilization (IVF) outcome. It is now necessary to evaluate its clinical usefulness in individual follicles. Objectives To evaluate the clinical value of PROK1 secretion in individual FF to predict oocyte competence. To determine the impact of follicular size, oocyte maturity, and gonadotropin treatments on PROK1 secretion. Design and setting Prospective cohort study from May 2015 to May 2017 at the University Hospital of Grenoble. Patients A total of 69 infertile couples underwent IVF. Intervention(s) Collection of 298 individual FF from 44 women undergoing IVF; 52 individual cumulus cell (CC) samples and 15 CC primary cultures from 25 women undergoing IVF-intracytoplasmic sperm injection (ICSI). Main Outcome Measure(s) Oocyte competence was defined as the ability to sustain embryo development to the blastocyst stage. Follicular size was measured by 2D-sonography. PROK1 concentration was quantified by ELISA assay. Results PROK1 concentration was correlated to follicular size (r = 0.85, P = 2.2 × 10−16). Normalized PROK1 concentration in FF was predictive of subsequent oocyte competence (AUROC curve = 0.76 [95% CI, 0.69–0.83]; P = 1.7 × 10−9), irrespectively of day-2 embryo morphokinetic parameters. The expression and secretion of PROK1 were increased in FF and CC of mature oocytes (P < 0.01). Follicle Stimulating Hormone and hCG up-regulated PROK1 secretion in CC primary cultures (P < 0.01; P < 0.05), probably through the cAMP pathway (P < 0.01). Conclusions PROK1 quantification in individual FF could constitute a new predictive biomarker of oocyte competence in addition with embryo morphokinetic parameters. Trial registration number none.

Roles of miR-10a-5p and miR-103a-3p, Regulators of BDNF Expression in Follicular Fluid, in the Outcomes of IVF-ET

“…According to Canosa, et al, reduced levels of Cx43 expression in the cumulus cells, coupled with increased expression of the BMP-15 mRNA, are considered markers of a higher probability of blastocyst development on day 5 (28). Alfaidy, et al identified PROK1 expression levels in individual FF samples as a predictor the in vitro fertilization (IVF) outcomes (29). Moreover, the expression of some non-coding RNAs, such as miR-451, in FF samples was positively correlated with the quality of blastocyst-stage embryos obtained from patients with endometriosis (30).…”

“…Alfaidy, et al. identified PROK1 expression levels in individual FF samples as a predictor the in vitro fertilization (IVF) outcomes ( 29 ). Moreover, the expression of some non-coding RNAs, such as miR-451, in FF samples was positively correlated with the quality of blastocyst-stage embryos obtained from patients with endometriosis ( 30 ).…”

Novel Insights into Prokineticin 1 Role in Pregnancy-related Diseases

“…Additionally, concentration of PROK1 protein in the follicular fluid is relevant to the follicular size and is predictive of the oocyte competence 21 . Follicle Stimulating Hormone and hCG up-regulated PROK1 protein secretion in cumulus cell primary cultures, probably through the cAMP pathway 21 . Successful embryo implantation may be predicted by PROK1 concentration in the follicular fluid and fertilization culture media in conventional in vitro fertilization-embryo transfer 22 .…”

Therapeutic Potential of Targeting Prokineticin Receptors in Diseases

“…Similarly, transgenic mice overexpressing PKR2 in their cardiomyocytes (TG-PKR2) showed hypertrophy and impaired endothelial integrity related to paracrine regulation ( Urayama et al, 2009 ). Overall, pressure overload-mediated maintenance of PKR2 signaling in cardiomyocytes contributes to cardiac hypertrophy via autocrine signaling and to vascular rarefaction via cardiac cytokine-mediated communication between cardiomyocytes and ECs ( Guilini et al, 2010 ; Alfaidy et al, 2019 ). In ECs cultured in vitro, activation of PKR2, unlike PKR1, does not induce angiogenesis but couples to G α 12-13-mediated degradation of zonula occludens one, a cell-cell adhesion molecule, at tight junctions and forms a fenestration of ECs.…”

“…PK1 and PK2 signaling have been reported to be associated with physiologic and pathologic aspects of the reproductive system ( Ferrara et al, 2004 ; Brouillet et al, 2010 , 2012a, b , 2013 ; Dunand et al, 2014 ; Alfaidy, 2016 ; Alfaidy et al, 2019 ). PK2 directly controls the migration of GnRH neurons, which affects the development of the female and male reproductive organs ( Dodé et al, 2006 ; Dodé and Rondard, 2013 ), while PK1 mainly controls female reproductive functions, especially those associated with pregnancy.…”