Transcription profile of the insulin-like growth factor signaling pathway during human ovarian follicular development
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Transcription profile of the insulin-like growth factor signaling pathway during human ovarian follicular development. / Bøtkjær, Jane Alrø; Pors, Susanne Elisabeth; Petersen, Tonny Studsgaard; Kristensen, Stine Gry; Jeppesen, Janni Vikkelsø; Oxvig, Claus; Andersen, Claus Yding.
In: Journal of Assisted Reproduction and Genetics, Vol. 36, No. 5, 05.2019, p. 889-903.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Transcription profile of the insulin-like growth factor signaling pathway during human ovarian follicular development
AU - Bøtkjær, Jane Alrø
AU - Pors, Susanne Elisabeth
AU - Petersen, Tonny Studsgaard
AU - Kristensen, Stine Gry
AU - Jeppesen, Janni Vikkelsø
AU - Oxvig, Claus
AU - Andersen, Claus Yding
PY - 2019/5
Y1 - 2019/5
N2 - PURPOSE: The 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.METHODS: Gene 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).RESULTS: The 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.CONCLUSIONS: This 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.
AB - PURPOSE: The 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.METHODS: Gene 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).RESULTS: The 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.CONCLUSIONS: This 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.
KW - Adult
KW - Cells, Cultured
KW - Female
KW - Follicular Fluid/metabolism
KW - Granulosa Cells/metabolism
KW - Humans
KW - Insulin-Like Growth Factor Binding Proteins/genetics
KW - Neoplasms/genetics
KW - Ovarian Follicle/metabolism
KW - Pregnancy
KW - Signal Transduction
KW - Transcriptome
KW - Young Adult
U2 - 10.1007/s10815-019-01432-x
DO - 10.1007/s10815-019-01432-x
M3 - Journal article
C2 - 30877600
VL - 36
SP - 889
EP - 903
JO - Journal of Assisted Reproduction and Genetics
JF - Journal of Assisted Reproduction and Genetics
SN - 1058-0468
IS - 5
ER -
ID: 235152275