Detection of soluble ST2 in human follicular fluid and luteinized granulosa cells

PLoS One. 2013 Sep 10;8(9):e74385. doi: 10.1371/journal.pone.0074385. eCollection 2013.

Abstract

Follicular fluid (FF) contains various cytokines that are involved with folliculogenesis, some of which have been shown to be associated with oocyte quality and the implantation potential of a resulting embryo. Several IL-1 family members have previously been identified in FF. This study investigates a newly identified member of the family, IL-33, and its receptor ST2, comparing values to those of FF Granulocyte-Colony Stimulating Factor (G-CSF)--a known predictor of Assisted Reproductive Technology (ART) success. FF was collected from patients undergoing in vitro fertilisation/intra-cytoplasmic sperm injection (IVF/ICSI) at oocyte retrieval to analyse IL-33 and sST2 expression in human follicles. sST2, but not IL-33, is highly increased in the FF compared to plasma levels (up to 7.9-fold), with higher levels in larger follicles (p<0.05). Furthermore, we identify that human luteinised granulosa cells are one possible source of the FF sST2, as these cells express and secrete sST2 when cultured ex vivo. FF associated with oocytes which when fertilised develop into good quality embryos have higher sST2 levels than those which are graded average (p<0.01). These embryos were transferred to the patient and levels of FF sST2 compared between successful and unsuccessful ICSI cycles. However unlike G-CSF, sST2 levels cannot be used to predict cycle outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Embryo, Mammalian
  • Female
  • Follicular Fluid / chemistry
  • Follicular Fluid / metabolism*
  • Gene Expression
  • Granulosa Cells / cytology
  • Granulosa Cells / metabolism*
  • Humans
  • Infertility, Female
  • Infertility, Male
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins / genetics*
  • Interleukins / metabolism
  • Luteinization / physiology
  • Male
  • Oocytes / cytology*
  • Oocytes / physiology
  • Pregnancy
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism
  • Reproductive Techniques, Assisted*
  • Solubility
  • Sperm Injections, Intracytoplasmic
  • Treatment Outcome

Substances

  • IL1RL1 protein, human
  • IL33 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins
  • Receptors, Cell Surface

Grants and funding

This work was supported by the Wellbeing of Women (grant number RG1326), the Oxfordshire Health Services Research Committee (OSHRC 1085, charitable fund number 8234) and the Agence de la Biomédecine and Uteron SA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.