Anti-oxidative function of follicular fluid HDL and outcomes of modified natural cycle-IVF

Ruxandra A Nagy,Josephine L C Anderson,Aafke P A Van Montfoort,Henk Groen,Daniela Andrei,Irene Homminga,Rima H Mistry,Uwe J F Tietge,Annemieke Hoek

doi:10.1038/s41598-019-49091-3

Abstract

High density lipoproteins (HDL) are the main cholesterol carriers in follicular fluid (FF), the natural environment of oocyte development. Additionally, HDL have critical biological functions such as anti-oxidative capacity, which have not been studied in reproduction. Therefore, this study aimed to investigate whether the anti-oxidative function of FF-HDL is associated with fertility outcomes. From 253 women undergoing modified natural cycle (MNC)- IVF at a single academic centre FF and plasma were collected (n = 375 cycles). Anti-oxidative function of FF was mainly attributable to HDL (n = 8; 83%). FF-HDL had a higher anti-oxidative function than plasma HDL (n = 19, P < 0.001) coinciding with increased vitamin E and sphingosine 1 phosphate content (P = 0.028 each). Proteomic analysis indicated no significant differences in major anti-oxidative proteins such as paraoxonase 1, apolipoprotein (apo) A-I or apoA-IV between FF-HDL and matched plasma-HDL (n = 5), while apoC-III, apoE and apoC-II were relatively lower in FF-HDL. Finally, FF-HDL anti-oxidative function was related to a decrease in the odds of the oocyte undergoing normal fertilization, an association that persisted after adjustment for confounders (odds ratio 0.97 (0.93–1), P = 0.041). In conclusion, FF-HDL has considerable anti-oxidative properties that might be relevant for embryo quality.

Highlights

The role of high density lipoproteins (HDL) in health and disease is traditionally viewed in the context of protection against atherosclerotic cardiovascular disease (CVD)
Its composition has been linked to oocyte growth and quality, and variations in the metabolic profile of follicular fluid (FF), such as lipoproteins, certain bile acid species, glucose, lactate and other metabolites are associated with the developmental potential of embryos in in vitro fertilization (IVF) procedures[3,4,5]
The results of this study demonstrate that (i) FF has anti-oxidative capacity of which the majority is attributable to the presence of High density lipoproteins (HDL), and (ii) an increase in FF anti-oxidative function was associated with a decreased chance for the oocyte to undergo normal fertilization

Summary

Introduction

The role of high density lipoproteins (HDL) in health and disease is traditionally viewed in the context of protection against atherosclerotic cardiovascular disease (CVD). While the body of literature on HDL function in the cardiovascular field is increasing, this concept remains insufficiently explored in other fields where HDL might play a physiological role, such as reproduction[2]. Unfavourable metabolic conditions including obesity, insulin resistance or other components of the metabolic syndrome are associated with decreased fertility on the one hand and with altered plasma HDL anti-oxidative function on the other[10,15,16,17,18,19]. Despite the biological activities of HDL and their abundant presence in FF, the anti-oxidative properties of HDL in FF and their potential association with parameters of fertility have not been explored far. In contrast to classic hyperstimulation IVF, in MNC-IVF (a setting close to normal reproductive physiology) it is possible to associate each FF sample collected with one specific oocyte and subsequently one embryo

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Conclusion