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

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@article{5ac7542d80594d94aa5aa0b7f8183524,
title = "Transcription profile of the insulin-like growth factor signaling pathway during human ovarian follicular development",
abstract = "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.",
keywords = "Human ovarian follicles, IGF system, IGFBPs, PAPP-A, Stanniocalcins, Signal Transduction, Humans, Cells, Cultured, Transcriptome, Neoplasms/genetics, Pregnancy, Young Adult, Follicular Fluid/metabolism, Adult, Female, Granulosa Cells/metabolism, Ovarian Follicle/metabolism, Insulin-Like Growth Factor Binding Proteins/genetics",
author = "B{\o}tkj{\ae}r, {Jane Alr{\o}} and Pors, {Susanne Elisabeth} and Petersen, {Tonny Studsgaard} and Kristensen, {Stine Gry} and Jeppesen, {Janni Vikkels{\o}} and Claus Oxvig and Andersen, {Claus Yding}",
year = "2019",
month = "5",
doi = "10.1007/s10815-019-01432-x",
language = "English",
volume = "36",
pages = "889--903",
journal = "Journal of Assisted Reproduction and Genetics",
issn = "1058-0468",
publisher = "Springer New York LLC",
number = "5",

}

RIS

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 - Human ovarian follicles

KW - IGF system

KW - IGFBPs

KW - PAPP-A

KW - Stanniocalcins

KW - Signal Transduction

KW - Humans

KW - Cells, Cultured

KW - Transcriptome

KW - Neoplasms/genetics

KW - Pregnancy

KW - Young Adult

KW - Follicular Fluid/metabolism

KW - Adult

KW - Female

KW - Granulosa Cells/metabolism

KW - Ovarian Follicle/metabolism

KW - Insulin-Like Growth Factor Binding Proteins/genetics

U2 - 10.1007/s10815-019-01432-x

DO - 10.1007/s10815-019-01432-x

M3 - Journal article

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: 57199618