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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.

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



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.


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.


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).


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.


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

[Indexed for MEDLINE]

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