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

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

doi:10.1016/j.mce.2019.110522

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

Mol Cell Endocrinol. 2019 Sep 15:495:110522. doi: 10.1016/j.mce.2019.110522. Epub 2019 Jul 26.

Authors

Liv la Cour Poulsen¹, Indira Pla², Aniel Sanchez², Marie Louise Grøndahl³, György Marko-Varga⁴, Claus Yding Andersen⁵, Anne Lis Mikkelsen Englund⁶, Johan Malm²

Affiliations

¹ Zealand Fertility Clinic, Zealand University Hospital, Lykkebækvej 14, 4600 Køge, Denmark. Electronic address: [email protected].
² Clinical Protein Science & Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund University, BMC D13, 221 84 Lund, Sweden; Section for Clinical Chemistry, Department of Translational Medicine, Lund University, Skåne University Hospital Malmö, 205 02 Malmö, Sweden.
³ Fertility Clinic, University Hospital of Copenhagen, Herlev and Gentofte Hospital, Herlev Ringvej 75, 2730 Herlev, Denmark.
⁴ Clinical Protein Science & Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund University, BMC D13, 221 84 Lund, Sweden; Section for Clinical Chemistry, Department of Translational Medicine, Lund University, Skåne University Hospital Malmö, 205 02 Malmö, Sweden; Department of Surgery, Tokyo Medical University, 6-7-1 Nishishinjiku Shinjiku-ku, Japan.
⁵ Laboratory of Reproductive Biology, University Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
⁶ Zealand Fertility Clinic, Zealand University Hospital, Lykkebækvej 14, 4600 Køge, Denmark.

PMID: 31356852
DOI: 10.1016/j.mce.2019.110522

Abstract

Follicular fluid (FF) acts as a vehicle for paracrine signalling between somatic cells of the follicle and the oocyte. To investigate changes in the protein composition of FF during ovulation, we conducted a prospective cohort study including 25 women undergoing fertility treatment. Follicular fluid was aspirated either before or 12, 17, 32 or 36 h after induction of ovulation (five patients per time point). Liquid chromatography-mass spectrometry was used to identify and quantify FF proteins. In total, 400 proteins were identified and the levels of 40 proteins changed significantly across ovulation, evaluated by analysis of covariance (adjusted p < 0.05) and on-off expression patterns. The majority peaked after 12-17 h, e.g., AREG (p < 0.0001), TNFAIP6 (p < 0.0001), and LDHB (p = 0.0316), while some increased to peak after 36 h e.g., ACPP (p < 0.0001), TIMP1 (p < 0.0001) and SERPINE1 (p = 0.0002). Collectively, this study highlights proteins and pathways of importance for ovulation and oocyte competence in humans.

Keywords: Follicular fluid; Human; Oocyte maturation; Ovulation; Proteome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Female
Follicular Fluid / metabolism*
Gene Ontology
Humans
Ovulation / physiology*
Principal Component Analysis
Protein Interaction Mapping
Proteomics*
Young Adult