Is there a correlation between follicle size and gene expression in cumulus cells and is gene expression an indicator of embryo development?

Reprod Biol Endocrinol. 2018 Jul 21;16(1):69. doi: 10.1186/s12958-018-0388-0.

Abstract

Background: In an article published in 2017, we discussed the results of the first part of our study into the morphokinetic development of embryos in relation to follicle diameter and homogeneity of follicular development. Our findings showed that embryos coming from small follicles in heterogeneous cycles had significantly higher rates of arrest or failure to reach blastocyst than embryos coming from large follicles in homogenous cycles. The aim of this further study was to investigate the relationship between follicular size and gene expression of cumulus cells (CCs) and evaluate whether gene expression could be an indicator of embryo development.

Methods: This study was based on 2495 COCs from 184 patients. CC expressions of five genes (TNFAIP6, PTGS2, HAS2, PTX3 and GDF9) were studied by generalized linear mixed models (GLMMs) regarding follicular size. CC expressions were then separately analysed regarding patient-specific variables (age, BMI, AMH and follicular size) in relation to embryos reaching blastocyst (eRB) or top or good quality blastocysts (TQ + GQ) using GLMMs with logit link.

Results: Follicular size significantly correlated with the potential of an oocyte to develop into a blastocyst: oocytes developing from large follicles were more than twice as likely to develop into an eRB than oocytes from small follicles (p < 0.001). Gene expression of HAS2 and GDF9 correlated with blastocyst quality when separately evaluated with follicular size and the patient specific variables of age, BMI and AMH. However, no such correlation was found in other gene expressions studied.

Conclusions: Our findings suggest that differences in the expression of genes studied could be related to follicular size rather than to embryo quality. Although gene expression of HAS2 and GDF9 correlated with blastocyst quality, the only variable correlating with eRB and TQ and GQ blastocysts for each of these five models was follicular size.

Trial registration: This prospective cohort study was registered at clinicaltrials.gov (NCT02230449).

Keywords: Blastocyst; Cumulus cells; Follicular size; Gene expression.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Age Factors
  • Anti-Mullerian Hormone / metabolism
  • Body Mass Index
  • C-Reactive Protein / genetics
  • C-Reactive Protein / metabolism
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cohort Studies
  • Cumulus Cells / metabolism*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Embryonic Development / genetics*
  • Female
  • Gene Expression*
  • Growth Differentiation Factor 9 / genetics
  • Growth Differentiation Factor 9 / metabolism
  • Humans
  • Hyaluronan Synthases / genetics
  • Hyaluronan Synthases / metabolism
  • Oocytes / cytology
  • Oocytes / growth & development
  • Ovarian Follicle / anatomy & histology*
  • Ovarian Follicle / growth & development
  • Ovarian Follicle / metabolism
  • Serum Amyloid P-Component / genetics
  • Serum Amyloid P-Component / metabolism

Substances

  • Cell Adhesion Molecules
  • GDF9 protein, human
  • Growth Differentiation Factor 9
  • Serum Amyloid P-Component
  • TNFAIP6 protein, human
  • PTX3 protein
  • Anti-Mullerian Hormone
  • C-Reactive Protein
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • HAS2 protein, human
  • Hyaluronan Synthases

Associated data

  • ClinicalTrials.gov/NCT02230449

Grants and funding