Cytokines and chemokines in follicular fluids and potential of the corresponding embryo: the role of granulocyte colony-stimulating factor

Lédée, Nathalie; Lombroso, Raoul; Lombardelli, Letizia; Selva, J.; Dubanchet, Sylvie; Chaouat, Gérard; Frankenne, Françis; Foidart, Jean‐Michel; Maggi, Enrico; Romagnani, Sergio; Ville, Y.; Piccinni, Marie‐Pierre

doi:10.1093/humrep/den192

Cited by 123 publications

(77 citation statements)

References 49 publications

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“…A positive association of IL-6 with oocyte maturation [31] and IL-1β with embryo development and pregnancy [32] is documented. A majority of findings have indicated that IL-12 is negatively associated with folliculogenesis, oocyte quality, and implantation [30,33,34]. TNF-α, reported to be significantly higher in follicular fluids corresponding to poor-quality oocytes and embryos, possibly deteriorates the microenvironment in the follicle [35,36].…”

Section: Discussionmentioning

confidence: 99%

Intrafollicular interleukin-8, interleukin-12, and adrenomedullin are the promising prognostic markers of oocyte and embryo quality in women with endometriosis

Singh

Dutta

Chattopadhyay

et al. 2016

J Assist Reprod Genet

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Purpose The study aimed to investigate key intrafollicular prognostic factors among various cytokines and angiogenic molecules for prediction of mature oocytes and good-quality embryos in women with endometriosis undergoing in vitro fertilization (IVF). Methods Paired follicular fluid and serum samples were collected from 200 women with advanced stage endometriosis and 140 normal ovulating women during oocyte retrieval. The concentrations of cytokines (pro-inflammatory: IL-1β, TNF-α, IL-2, IL-8, IL-12, IFN-γ; anti-inflammatory: IL-4, IL-6, IL-10) and angiogenic molecules (vascular endothelial growth factor (VEGF), adrenomedullin, angiogenin) were determined in follicular fluid and serum using ELISA. Expression of these molecules was subjected to multivariate analysis for the identification of major predictive markers of oocyte and embryo quality. Receiver operating characteristic (ROC) curve was applied to determine the best cutoff point for the discrimination between mature and immature oocytes in these women. Results Significant increases in levels of cytokines and angiogenic molecules were observed in women with endometriosis compared to controls (P < 0.001). From the validated partial least squares-discriminant analysis (PLS-DA) model, IL-8, IL-12, and adrenomedullin were identified as the most important factors contributing to endometriosis and were negatively associated with oocyte maturity and embryo quality. Conclusion The levels of IL-8, IL-12, and adrenomedullin may be good indicators of embryo and oocyte quality in endometriosis patients undergoing IVF. Further studies are necessary to ascertain the potential of these markers for oocyte and embryo developmental competence which may help improve the chances of a successful IVF in endometriosis patients.

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Section: Discussionmentioning

confidence: 99%

Intrafollicular interleukin-8, interleukin-12, and adrenomedullin are the promising prognostic markers of oocyte and embryo quality in women with endometriosis

Singh

Dutta

Chattopadhyay

et al. 2016

J Assist Reprod Genet

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“…The quantitative determination of cytokines was performed with a bead-based multiplex immunoassay, as previously described (Lédée et al 2008). Briefly a bead-based multiplex immunoassay (Bio-Rad) and a Bioplex 200 system (Bio-Rad; Luminex Map Technology) were used to measure simultaneously in cell culture supernatants the concentrations of the following cytokines and chemokines: IL1b, IL1Ra, IL2, IL4, IL5, IL6, IL8, IL9, IL10, IL12, IL13, IL15, IL17A, IFN-g, TNFa, G-CSF, GM-CSF, VEGF, PDGF, basic fibroblast growth factor (bFGF) interferon g/inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), RANTES, eotaxin, macrophage inflammatory protein-1a (MIP-1a), and MIP-1b.…”

Section: Determination Of Cytokine and Chemokine Concentrationsmentioning

confidence: 99%

Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells

Vignozzi

Cellai²,

Santi³

et al. 2012

Journal of Endocrinology

127

107

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Progression of benign prostatic hyperplasia (BPH) involves chronic inflammation and immune dysregulation. Preclinical studies have demonstrated that prostate inflammation and tissue remodeling are exacerbated by hypogonadism and prevented by testosterone supplementation. We now investigated whether, in humans, hypogonadism was associated with more severe BPH inflammation and the in vitro effect of the selective androgen receptor agonist dihydrotestosterone (DHT) on cultures of stromal cells derived from BPH patients (hBPH). Histological analysis of inflammatory infiltrates in prostatectomy specimens from a cohort of BPH patients and correlation with serum testosterone level was performed. Even after adjusting for confounding factors, hypogonadism was associated with a fivefold increased risk of intraprostatic inflammation, which was also more severe than that observed in eugonadal BPH patients. Triggering hBPH cells by inflammatory stimuli (tumor necrosis factor a, lipopolysaccharide, or CD4 C T cells) induced abundant secretion of inflammatory/growth factors (interleukin 6 (IL6), IL8, and basic fibroblast growth factor (bFGF)). Co-culture of CD4 C T cells with hBPH cells induced secretion of Th1 inducer (IL12), Th1-recruiting chemokine (interferon g inducible protein 10, IP10), and Th2 (IL9)-and Th17 (IL17)-specific cytokines. Pretreatment with DHT inhibited NF-kB activation and suppressed secretion of several inflammatory/growth factors, with the most pronounced effects on IL8, IL6, and bFGF. Reduced inflammatory cytokine production by testosterone cells, an increase in IL10, and a significant reduction of testosterone cells proliferation suggested that DHT exerted a broad antiinflammatory effect on testosterone cells. In conclusion, our data demonstrate that DHT exerts an immune regulatory role on human prostatic stromal cells, inhibiting their potential to actively induce and/or sustain autoimmune and inflammatory responses.

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“…Many couples still remain unsuccessful after several IVF attempts causing deep effect on quality of life and a heavy financial burden (Zeyneloglu & Onalan 2014). With the recent advances in understanding the important role of granulocyte colony-stimulating factor (GCSF) in reproduction, and the detection of GCSF receptors in placental cytotrophoblasts, syncytiotrophoblasts, decidual stromal cells, endometrial gland cells, and follicular cells (Saito et al 1994, Miyama et al 1998, McCracken et al 1999, Salmassi et al 2005, Ledee et al 2008, Rahmati et al 2014, GCSF started to attract attentions in gynecology, especially in patients with recurrent abortions and/or infertility.…”

Section: Introductionmentioning

confidence: 99%

Granulocyte colony-stimulating factor in repeated IVF failure, a randomized trial

Aleyasin¹,

Abediasl²,

Nazari³

et al. 2016

Reproduction

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Recent studies have revealed key roles for granulocyte colony-stimulating factor (GCSF) in embryo implantation process and maintenance of pregnancy, and some studies showed promising results by using local intrauterine infusion of GCSF in patients undergoing in vitro fertilization (IVF). This multicenter, randomized, controlled trial included 112 infertile women with repeated IVF failure to evaluate the efficacy of systemic single-dose subcutaneous GCSF administration on IVF success in these women. In this study, the Long Protocol of ovarian stimulation was used for all participants. Sealed, numbered envelopes assigned 56 patients to receive subcutaneous 300 µg GCSF before implantation and 56 in the control group. The implantation (number of gestational sacs on the total number of transferred embryos), chemical pregnancy (positive serum β-HCG), and clinical pregnancy (gestational sac and fetal heart) rates were compared between the two groups. This trial is registered at www.irct.ir (IRCT201503119568N11). The successful implantation (18% vs 7.2%, P = 0.007), chemical pregnancy (44.6% vs 19.6%, P = 0.005), and clinical pregnancy (37.5% vs 14.3%, P = 0.005) rates were significantly higher in the intervention group than in the control group. After adjustment for participants' age, endometrial thickness, good-quality oocyte counts, number of transferred embryos, and anti-Mullerian hormone levels, GCSF treatment remained significantly associated with successful implantation (OR = 2.63, 95% CI = 1.09-6.96), having chemical pregnancy (OR= 2.74, 95% CI = 1.11-7.38) and clinical pregnancy (OR = 2.94, 95% CI = 1.23-8.33). In conclusion, administration of single-dose systemic subcutaneous GCSF before implantation significantly increases the IVF success, implantation, and pregnancy rates in infertile women with repeated IVF failure.

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Cytokines and chemokines in follicular fluids and potential of the corresponding embryo: the role of granulocyte colony-stimulating factor

Cited by 123 publications

References 49 publications

Intrafollicular interleukin-8, interleukin-12, and adrenomedullin are the promising prognostic markers of oocyte and embryo quality in women with endometriosis

Intrafollicular interleukin-8, interleukin-12, and adrenomedullin are the promising prognostic markers of oocyte and embryo quality in women with endometriosis

Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells

Granulocyte colony-stimulating factor in repeated IVF failure, a randomized trial

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