Progressive changes in human follicular fluid composition over the course of ovulation: quantitative proteomic analyses

Poulsen, Liv la Cour; Pla, Indira; Sánchez, Aniel; Grøndahl, Marie Louise; Markó-Varga, György; Andersen, Claus Yding; Englund, Anne Lis Mikkelsen; Malm, Johan

doi:10.1016/j.mce.2019.110522

Cited by 31 publications

(16 citation statements)

References 68 publications

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“…In contrast to assessments directly performed on oocytes or embryos (37,38), FF, as the microenvironment where oogenesis and oocyte maturation take place, provides a noninvasive approach to estimate oocyte quality at a relatively early stage. And the efficacy of biomarkers found in FF has been confirmed in previous researches (39). In a retrospective cohort study, decorin in FF (F-DCN) was measured quantitively and showed a significantly lower content in FF of fertilized oocytes than that in unfertilized ones, which suggested the possibility and practicability of FF components as potential biomarkers to predict the quality of oocytes collected from corresponding follicles (40).…”

Section: Discussionsupporting

confidence: 58%

Resolvin E1 in Follicular Fluid Acts as a Potential Biomarker and Improves Oocyte Developmental Competence by Optimizing Cumulus Cells

Zhang

Zhu

et al. 2020

Front. Endocrinol.

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Metabolic profile of follicular fluid (FF) has been investigated to look for biomarkers for oocyte quality. Resolvin E1 (RvE1), a potent pro-resolving mediator, was reported to have protective action in cell function. The study aimed to examine the predictive value of RvE1 for oocyte quality and to explore the cellular mechanism of RvE1 in improving oocyte competence. Metabolic profiles of 80 FF samples showed a higher level of RvE1 in group A (blastocysts scored ≥ B3BC and B3CB according to Gardner's blastocyst scoring system, N = 36) than that of group B (blastocysts scored < B3BC and B3CB, N = 44, P = 0.0018). The receiver operating characteristic (ROC) curve analysis showed that RvE1 level in FF below 8.96 pg/ml (AUC:0.75; 95%CI: 0.64-0.86; P = 0.00012) could predict poor oocyte quality with specificity of 97.22%, suggesting RvE1 as a potential biomarker to exclude inferior oocytes. Besides, the level of RvE1 was found to be significantly lower in FF than in serum (57.49 to 17.62 pg/ml; P = 0.0037) and was gradually accumulated in the culture medium of cumulus cells (CCs) during cell culture, which indicated that RvE1 came from both blood exudates and local secretion. The in vitro experiment revealed the cellular mechanism of RvE1 in improving oocyte quality by decreasing the cumulus cell apoptotic rate and increasing cell viability and proliferation. It is the first time that the role of RvE1 in reproduction is explored. In conclusion, RvE1 is valuable as a potential exclusive biomarker for oocyte selection and plays a role in improving oocyte quality.

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Section: Discussionsupporting

confidence: 58%

Resolvin E1 in Follicular Fluid Acts as a Potential Biomarker and Improves Oocyte Developmental Competence by Optimizing Cumulus Cells

Zhang

Zhu

et al. 2020

Front. Endocrinol.

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“…There is limited evidence for the downregulation of HSPG2 expression at the mRNA level by ADAMTS1. However, studies reported that perlecan in follicular fluids reached a peak at 12 h after injecting hCG [47] and may have a close relationship with oocyte developmental competence [48][49][50]. Because perlecan in follicular fluids is derived from GCs, it will be interesting to investigate correlations between HSPG2 mRNA levels in human CCs and oocyte developmental competence.…”

Section: Discussionmentioning

confidence: 99%

ADAMTS1 and HSPG2 mRNA levels in cumulus cells are related to human oocyte quality and controlled ovarian hyperstimulation outcomes

Jin

Yang

et al. 2020

J Assist Reprod Genet

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Purpose The study investigated potential correlations between the expression levels of ADAMTS1 and HSPG2 in cumulus cells (CCs) and controlled ovarian hyperstimulation (COH) outcomes. Methods RT-PCR was used to determine ADAMTS1 and HSPG2 mRNA levels in mice CCs at different timepoints (0, 4, 8, 12, and 16 h) after human chorionic gonadotropin (hCG) injection, and in CCs after RNAi treatment. Women with polycystic ovary syndrome (PCOS) (n = 45) and normal ovulatory controls (n = 103) undergoing IVF/ICSI were recruited. Relative ADAMTS1 and HSPG2 mRNA levels were measured by RT-PCR. Moreover, correlations of ADAMTS1 and HSPG2 levels with COH outcomes were analyzed. Results At different timepoints after hCG treatment, ADAMTS1 mRNA had the highest level at 12 h, whereas HSPG2 showed opposite profiles to ADAMTS1 with the lowest level at 12 h. HSPG2 expression was upregulated after ADAMTS1 RNAi treatment The PCOS group had higher HSPG2 and lower ADAMTS1 expression levels than controls. In normal ovulatory women (control group), a higher expression of ADAMTS1 and lower expression of HSPG2 were associated with more mature oocytes, transplantable embryos, and good quality embryos, whereas higher transplantable embryo rates and good quality embryo rates were obtained only with lower HSPG2 expression. ROC curves showed the co-measurement of ADAMTS1 and HSPG2 had a better predictive power than separate analyses. Conclusion The dynamic profiles of ADAMTS1 and HSPG2 were inversely correlated in CCs. In PCOS and normal ovulatory patients, higher ADAMTS1 and lower HSPG2 expression levels in CCs were related to better COH outcomes.

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“…It is worth noting that the observed declines in numerous cytokeratins (KRT2, KRT3, KRT5, KRT10, KRT17, KRT18, and KRT75) within the follicular fluid may be further evidence of changes occurring within follicular cells of hyperthermic cows. Others have documented the presence of cytokeratins in follicular fluid [70–73]. Cytokeratins within follicular fluid could be attributed to granulosa cells releasing protein fragments as part of cell death [74] and/or after disintegration of cytokeratin filaments during gonadotropin-induced differentiation [75, 76]; both events are likely essential as the follicle reorganizes in preparation for ovulation.…”

Section: Discussionmentioning

confidence: 99%

Heat-induced hyperthermia impacts the follicular fluid proteome of the periovulatory follicle in lactating dairy cows

et al. 2019

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We hypothesized that heat-induced perturbations in cumulus cells surrounding the maturing oocyte may extend to the mural granulosa of the periovulatory follicle in the heat-stressed cow to subsequently the follicular fluid proteome. Lactating Holsteins were pharmacologically stimulated to have a dominant follicle that was capable of responding to a gonadotropin releasing hormone-induced luteinizing hormone surge. Following gonadotropin releasing hormone administration, cows were maintained at ~67 temperature humidity index (THI; thermoneutral conditions) or exposed to conditions simulating an acute heat stress event (71 to 86 THI; heat stress for ~12 h). Dominant follicle collection was conducted in the periovulatory period ~16 h after gonadotropin releasing hormone. Follicular fluid proteome from thermoneutral (n = 5) and hyperthermic (n = 5) cows was evaluated by quantitative tandem mass spectrometry (nano LC-MS/MS). We identified 35 differentially-abundant proteins. Functional annotation revealed numerous immune-related proteins. Subsequent efforts revealed an increase in levels of the proinflammatory mediator bradykinin in follicular fluid (P = 0.0456) but not in serum (P = 0.9319) of hyperthermic cows. Intrafollicular increases in transferrin (negative acute phase protein) in hyperthermic cows (P = 0.0181) coincided with a tendency for levels to be increased in the circulation (P = 0.0683). Nine out of 15 cytokines evaluated were detected in follicular fluid. Heat stress increased intrafollicular interleukin 6 levels (P = 0.0160). Whether hyperthermia-induced changes in the heat-stressed cow’s follicular fluid milieu reflect changes in mural granulosa, cumulus, other cell types secretions, and/or transudative changes from circulation remains unclear. Regardless of origin, heat stress/hyperthermia related changes in the follicular fluid milieu may have an impact on components important for ovulation and competence of the cumulus-oocyte complex contained within the periovulatory follicle.

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Progressive changes in human follicular fluid composition over the course of ovulation: quantitative proteomic analyses

Cited by 31 publications

References 68 publications

Resolvin E1 in Follicular Fluid Acts as a Potential Biomarker and Improves Oocyte Developmental Competence by Optimizing Cumulus Cells

Resolvin E1 in Follicular Fluid Acts as a Potential Biomarker and Improves Oocyte Developmental Competence by Optimizing Cumulus Cells

ADAMTS1 and HSPG2 mRNA levels in cumulus cells are related to human oocyte quality and controlled ovarian hyperstimulation outcomes

Heat-induced hyperthermia impacts the follicular fluid proteome of the periovulatory follicle in lactating dairy cows

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