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

Yijing Zhang,Jing Fu,Zhongyi Zhu,Wen He,Ronggui Qu,Xiandong Peng,Mingjiang Zhu,Aijie Xin,Xiaoxi Sun,He Li

doi:10.3389/fendo.2020.00210

Abstract

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=.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 thecellular mechanism of RvE1 in improvingoocyte qualityby decreasing the cumulus cellapoptotic rate and increasing cell viability and proliferation. It is the first time thatthe role of RvE1 in reproduction is explored. In conclusion, RvE1 is valuable as a potential exclusive biomarker for oocyte selection andplays a role in improving oocyte quality.

Highlights

With an increasing number of infertile couples worldwide, in vitro fertilization (IVF) has become the most effective treatment for infertility in both developed and developing countries
The results of receiver operating characteristic curve (ROC) analysis showed specificity of 97.2% and sensitivity of 25.0% (Figure 1C) with the optimal cutoff value of Resolvin E1 (RvE1) (8.96 pg/ml) in follicular fluid (FF) from both groups determined by the largest positive likelihood ratio (8.99; value of sensitivity divided by 1 - specificity; Figures 1B,C)
We revealed the positive association between RvE1 and oocyte quality, suggesting RvE1 as a candidate for FF biomarkers to exclude inferior oocytes

Summary

Introduction

With an increasing number of infertile couples worldwide, in vitro fertilization (IVF) has become the most effective treatment for infertility in both developed and developing countries. In an attempt to optimize the IVF outcome, recent researches have focused on the identification of non-invasive biomarkers to aid the selection of oocytes and embryos with superior quality and viability [3, 4]. Follicular fluid (FF), the relatively independent microenvironment of oocytes, is produced by the effusion of blood plasma and secretion of theca cells, granulosa cells as well as oocytes [5]. FF contains a series of metabolites critical for oocyte maturation and its variation in composition, to a certain extent, reflects oocyte developmental competence and embryo viability [6, 7]. The investigation into the metabolic profile of FF might provide potential biomarkers for oocyte and embryo quality which could be applied as a supplemental assessment method in assisted reproductive technology (ART)

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