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Effect of sphingosine-1-phosphate on activation of dormant follicles in murine and human ovarian tissue

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Pors, Susanne Elisabeth ; Harðardóttir, Lilja ; Olesen, Hanna Ørnes ; Riis, Malene Lundgaard ; Jensen, Lea Bejstrup ; Andersen, Astrid Sten ; Cadenas, Jesús ; Grønning, Annika Patricia ; Colmorn, Lotte Berdiin ; Dueholm, Margit ; Andersen, Claus Yding ; Kristensen, Stine Gry. / Effect of sphingosine-1-phosphate on activation of dormant follicles in murine and human ovarian tissue. In: Molecular Human Reproduction. 2020 ; Vol. 26, No. 5. pp. 301-311.

Bibtex

@article{5b943b03b3ef43b2b3ce8d051aa3860e,
title = "Effect of sphingosine-1-phosphate on activation of dormant follicles in murine and human ovarian tissue",
abstract = "In vitro activation of resting ovarian follicles, with the use of mechanical stress and/or pharmacological compounds, is an emerging and novel approach for infertility treatment. The aim of this study was to assess the sphingolipid, sphingosine-1-phosphate (S1P), as a potential in vitro activation agent in murine and human ovarian tissues and isolated follicles. Juvenile murine ovaries and donated human ovarian tissues, from 10 women undergoing ovarian tissue cryopreservation for fertility preservation, were incubated with or without 12 μM S1P for 3 h for quantitative PCR analysis, and 12 h for xenotransplantation or culture studies. Gene expression analyses were performed for genes downstream of the Hippo signaling pathway. Murine ovaries and isolated murine and human preantral follicles showed significantly increased mRNA expression levels of Ccn2/CCN2 following S1P treatment compared to controls. This increase was shown to be specific for the Hippo signaling pathway and for the S1P2 receptor, as co-treatment with Hippo-inhibitor, verteporfin and S1PR2 antagonist, JTE-013, reduced the S1P-induced Ccn2 gene expression in murine ovaries. Histological evaluation of human cortical tissues (5 × 5 × 1 mm; n = 30; three pieces per patient) xenografted for 6 weeks and juvenile murine ovaries cultured for 4 days (n = 9) or allografted for 2 weeks (n = 48) showed no differences in the distribution of resting or growing follicles in S1P-treated ovarian tissues compared to controls. Collectively, S1P increased Ccn2/CCN2 gene expression in isolated preantral follicles and ovarian tissue from mice and human, but it did not promote follicle activation or growth in vivo. Thus, S1P does not appear to be a potent in vitro activation agent under these experimental conditions.",
keywords = "follicle activation, hippo pathway, human ovarian tissue, sphingosine-1-phosphate, xenotransplantation",
author = "Pors, {Susanne Elisabeth} and Lilja Har{\dh}ard{\'o}ttir and Olesen, {Hanna {\O}rnes} and Riis, {Malene Lundgaard} and Jensen, {Lea Bejstrup} and Andersen, {Astrid Sten} and Jes{\'u}s Cadenas and Gr{\o}nning, {Annika Patricia} and Colmorn, {Lotte Berdiin} and Margit Dueholm and Andersen, {Claus Yding} and Kristensen, {Stine Gry}",
note = "{\textcopyright} The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.",
year = "2020",
month = may,
day = "15",
doi = "10.1093/molehr/gaaa022",
language = "English",
volume = "26",
pages = "301--311",
journal = "Molecular Human Reproduction",
issn = "1360-9947",
publisher = "Oxford University Press",
number = "5",

}

RIS

TY - JOUR

T1 - Effect of sphingosine-1-phosphate on activation of dormant follicles in murine and human ovarian tissue

AU - Pors, Susanne Elisabeth

AU - Harðardóttir, Lilja

AU - Olesen, Hanna Ørnes

AU - Riis, Malene Lundgaard

AU - Jensen, Lea Bejstrup

AU - Andersen, Astrid Sten

AU - Cadenas, Jesús

AU - Grønning, Annika Patricia

AU - Colmorn, Lotte Berdiin

AU - Dueholm, Margit

AU - Andersen, Claus Yding

AU - Kristensen, Stine Gry

N1 - © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

PY - 2020/5/15

Y1 - 2020/5/15

N2 - In vitro activation of resting ovarian follicles, with the use of mechanical stress and/or pharmacological compounds, is an emerging and novel approach for infertility treatment. The aim of this study was to assess the sphingolipid, sphingosine-1-phosphate (S1P), as a potential in vitro activation agent in murine and human ovarian tissues and isolated follicles. Juvenile murine ovaries and donated human ovarian tissues, from 10 women undergoing ovarian tissue cryopreservation for fertility preservation, were incubated with or without 12 μM S1P for 3 h for quantitative PCR analysis, and 12 h for xenotransplantation or culture studies. Gene expression analyses were performed for genes downstream of the Hippo signaling pathway. Murine ovaries and isolated murine and human preantral follicles showed significantly increased mRNA expression levels of Ccn2/CCN2 following S1P treatment compared to controls. This increase was shown to be specific for the Hippo signaling pathway and for the S1P2 receptor, as co-treatment with Hippo-inhibitor, verteporfin and S1PR2 antagonist, JTE-013, reduced the S1P-induced Ccn2 gene expression in murine ovaries. Histological evaluation of human cortical tissues (5 × 5 × 1 mm; n = 30; three pieces per patient) xenografted for 6 weeks and juvenile murine ovaries cultured for 4 days (n = 9) or allografted for 2 weeks (n = 48) showed no differences in the distribution of resting or growing follicles in S1P-treated ovarian tissues compared to controls. Collectively, S1P increased Ccn2/CCN2 gene expression in isolated preantral follicles and ovarian tissue from mice and human, but it did not promote follicle activation or growth in vivo. Thus, S1P does not appear to be a potent in vitro activation agent under these experimental conditions.

AB - In vitro activation of resting ovarian follicles, with the use of mechanical stress and/or pharmacological compounds, is an emerging and novel approach for infertility treatment. The aim of this study was to assess the sphingolipid, sphingosine-1-phosphate (S1P), as a potential in vitro activation agent in murine and human ovarian tissues and isolated follicles. Juvenile murine ovaries and donated human ovarian tissues, from 10 women undergoing ovarian tissue cryopreservation for fertility preservation, were incubated with or without 12 μM S1P for 3 h for quantitative PCR analysis, and 12 h for xenotransplantation or culture studies. Gene expression analyses were performed for genes downstream of the Hippo signaling pathway. Murine ovaries and isolated murine and human preantral follicles showed significantly increased mRNA expression levels of Ccn2/CCN2 following S1P treatment compared to controls. This increase was shown to be specific for the Hippo signaling pathway and for the S1P2 receptor, as co-treatment with Hippo-inhibitor, verteporfin and S1PR2 antagonist, JTE-013, reduced the S1P-induced Ccn2 gene expression in murine ovaries. Histological evaluation of human cortical tissues (5 × 5 × 1 mm; n = 30; three pieces per patient) xenografted for 6 weeks and juvenile murine ovaries cultured for 4 days (n = 9) or allografted for 2 weeks (n = 48) showed no differences in the distribution of resting or growing follicles in S1P-treated ovarian tissues compared to controls. Collectively, S1P increased Ccn2/CCN2 gene expression in isolated preantral follicles and ovarian tissue from mice and human, but it did not promote follicle activation or growth in vivo. Thus, S1P does not appear to be a potent in vitro activation agent under these experimental conditions.

KW - follicle activation

KW - hippo pathway

KW - human ovarian tissue

KW - sphingosine-1-phosphate

KW - xenotransplantation

UR - http://www.scopus.com/inward/record.url?scp=85084942823&partnerID=8YFLogxK

U2 - 10.1093/molehr/gaaa022

DO - 10.1093/molehr/gaaa022

M3 - Journal article

C2 - 32202615

VL - 26

SP - 301

EP - 311

JO - Molecular Human Reproduction

JF - Molecular Human Reproduction

SN - 1360-9947

IS - 5

ER -

ID: 61254911