Transcription profile of the insulin-like growth factor signaling pathway during human ovarian follicular development

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  • Jane Alro Botkjaer, University of Copenhagen
  • ,
  • Susanne Elisabeth Pors, University of Copenhagen
  • ,
  • Tonny Studsgaard Petersen, University of Copenhagen
  • ,
  • Stine Gry Kristensen, University of Copenhagen
  • ,
  • Janni Vikkelso Jeppesen, University of Copenhagen
  • ,
  • Claus Oxvig
  • Claus Yding Andersen, University of Copenhagen

PurposeThe IGF signaling cascade exerts important regulatory functions in human ovarian folliculogenesis. The scope of this study was to evaluate the transcription profile of insulin-like growth factor (IGF) genes during human ovarian follicle development and to analyze follicle fluid levels of key IGF proteins.MethodsGene expression profiling was performed with microarray gene analysis. The analysis was assessed from ovarian follicles and granulosa cells (GCs) obtained from isolated stage-specific human ovarian follicles, including preantral follicles, small antral follicles, and preovulatory follicles. Numerous genes involved in the IGF signaling pathway was evaluated and key genes were validated by qPCR from GCs. Protein levels of various IGF components of human follicular fluid (FF) were measured by ELISA and time-resolved immunofluorometric assays (TRIFMA).ResultsThe gene expression levels of PAPPA, IGF2, IGF receptors and intracellular IGF-activated genes increased with increasing follicle size. This was especially prominent in the late preovulatory stage where IGF2 expression peaked. Protein levels of intact IGF binding protein-4 decreased significantly in FF from large preovulatory follicles compared with small antral follicles concomitant with higher protein levels of PAPP-A. The IGF modulators IGF-2 receptor, IGFBPs, stanniocalcins, and IGF-2 mRNA binding proteins were all observed to be expressed in the different follicle stages.ConclusionsThis study confirms and highlights the importance of PAPP-A regulating bioactive IGF levels throughout folliculogenesis and especially for the high rate of granulosa cell proliferation and expression of key ovarian hormones important in the last part of the follicular phase of the menstrual cycle.

Original languageEnglish
JournalJournal of Assisted Reproduction and Genetics
Volume36
Issue5
Pages (from-to)889-903
Number of pages15
ISSN1058-0468
DOIs
Publication statusPublished - May 2019

    Research areas

  • IGF system, IGFBPs, PAPP-A, Stanniocalcins, Human ovarian follicles, PLASMA PROTEIN-A, HUMAN CHORIONIC-GONADOTROPIN, ROBUST MULTIARRAY ANALYSIS, PRE-ANTRAL FOLLICLES, HUMAN THECAL CELLS, GRANULOSA-CELLS, IGF-II, BINDING-PROTEIN, STIMULATES STEROIDOGENESIS

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