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Eur J Clin Invest. 2015 Aug;45(8):833-41. doi: 10.1111/eci.12478. Epub 2015 Jul 3.

Preconception folic acid use influences the follicle fluid proteome.

Author information

1
Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
2
Proteomics center, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
3
Clinical Chemistry, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
4
Department of Clinical Genetics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

Abstract

BACKGROUND:

The investigation of the human follicle fluid proteome has gained much interest in the search of new markers as predictors for in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) treatment outcome. Follicular fluid folate, as substrate of one carbon (1-C) metabolism, affects follicular metabolism and oocyte and embryo quality. From this background, we aim to identify a folate-related follicle fluid proteome that associates with IVF/ICSI treatment outcome.

METHODS:

In a nested case-control study embedded in a periconception cohort, we performed qualitative and quantitative proteomic analyses using nanoflow LC-MS/MS and TMT labelling in 30 monofollicular fluid samples from women undergoing IVF/ICSI treatment of which 15 used and 15 did not use a folic acid supplement. The protein data are analysed using scaffold proteome Software and differential abundances are expressed as Log2-fold change. Blood samples were obtained before and after treatment for determination of biomarkers of 1-C metabolism and estradiol.

RESULTS:

We identified 227 uniquely expressed proteins in follicular fluid. In folic acid supplement users compared to nonusers, we established a lower abundance of C-reactive protein (-2.03; P = < 0.01) and higher abundances of apolipoproteins from high-density lipoprotein (HDL), most notably A-I (+1.28; P = < 0.01) and C-I (+1.11; P = 0.016).

CONCLUSION:

Preconception folic acid supplement use is associated with suppression of the inflammatory pathway and upregulation of the HDL pathway in human follicular fluid, being a preferential source of cholesterol for steroid hormone synthesis. Studies are needed on the tissue specificity and on the beneficial effects of embryo quality and IVF/ICSI treatment outcome of the proteome of these pathways.

KEYWORDS:

Folic acid; follicle fluid; in vitro fertilization and intracytoplasmic sperm injection; proteomics

PMID:
26094490
DOI:
10.1111/eci.12478
[Indexed for MEDLINE]

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