Intracrine androgens enhance decidualization and modulate expression of human endometrial receptivity genes

Douglas A Gibson; Ioannis Simitsidellis; Fiona Cousins; Hilary O. D. Critchley; Philippa T. K. Saunders

doi:10.1038/srep19970

Intracrine androgens enhance decidualization and modulate expression of human endometrial receptivity genes

Douglas A Gibson, Ioannis Simitsidellis, Fiona Cousins, Hilary O. D. Critchley, Philippa T. K. Saunders

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

The endometrium is a complex, steroid-dependent tissue that undergoes dynamic cyclical remodelling. Transformation of stromal fibroblasts (ESC) into specialised secretory cells (decidualization) is fundamental to the establishment of a receptive endometrial microenvironment which can support and maintain pregnancy. Androgen receptors (AR) are present in ESC; in other tissues local metabolism of ovarian and adrenal-derived androgens regulate AR-dependent gene expression. We hypothesised that altered expression/activity of androgen biosynthetic enzymes would regulate tissue availability of bioactive androgens and the process of decidualization. Primary human ESC were treated in vitro for
1–8 days with progesterone and cAMP (decidualized) in the presence or absence of the AR antagonist flutamide. Time and treatment-dependent changes in genes essential for a) intra-tissue biosynthesis of androgens (5α-reductase/SRD5A1, aldo-keto reductase family 1 member C3/AKR1C3), b)
establishment of endometrial decidualization (IGFBP1, prolactin) and c) endometrial receptivity (SPP1, MAOA, EDNRB) were measured. Decidualization of ESC resulted in significant time-dependent changes in expression of AKR1C3 and SRD5A1 and secretion of T/DHT. Addition of flutamide significantly
reduced secretion of IGFBP1 and prolactin and altered the expression of endometrial receptivity markers. Intracrine biosynthesis of endometrial androgens during decidualization may play a key role in endometrial receptivity and offer a novel target for fertility treatment.

Original language	English
Journal	Scientific Reports
Early online date	28 Jan 2016
DOIs	https://doi.org/10.1038/srep19970
Publication status	E-pub ahead of print - 28 Jan 2016

Access to Document

10.1038/srep19970Licence: Creative Commons: Attribution (CC-BY)

srep19970
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Final published version, 1.25 MBLicence: Creative Commons: Attribution (CC-BY)

Impact of sex steroids on immune and vascular cell function in the reproductive system
Saunders, P.
MRC
1/10/11 → 31/03/17
Project: Research

Philippa Saunders
- p.saundersed.acuk
- Deanery of Clinical Sciences - Personal Chair of Reproductive Steroids
- Centre for Inflammation Research - Professor of Reproductive Steroids & Director of Postgraduate Research for CMVM
- Edinburgh Imaging
Person: Academic: Research Active

Cite this

@article{8e8d62eef3a54191b5acf133814925cb,

title = "Intracrine androgens enhance decidualization and modulate expression of human endometrial receptivity genes",

abstract = "The endometrium is a complex, steroid-dependent tissue that undergoes dynamic cyclical remodelling. Transformation of stromal fibroblasts (ESC) into specialised secretory cells (decidualization) is fundamental to the establishment of a receptive endometrial microenvironment which can support and maintain pregnancy. Androgen receptors (AR) are present in ESC; in other tissues local metabolism of ovarian and adrenal-derived androgens regulate AR-dependent gene expression. We hypothesised that altered expression/activity of androgen biosynthetic enzymes would regulate tissue availability of bioactive androgens and the process of decidualization. Primary human ESC were treated in vitro for1–8 days with progesterone and cAMP (decidualized) in the presence or absence of the AR antagonist flutamide. Time and treatment-dependent changes in genes essential for a) intra-tissue biosynthesis of androgens (5α-reductase/SRD5A1, aldo-keto reductase family 1 member C3/AKR1C3), b)establishment of endometrial decidualization (IGFBP1, prolactin) and c) endometrial receptivity (SPP1, MAOA, EDNRB) were measured. Decidualization of ESC resulted in significant time-dependent changes in expression of AKR1C3 and SRD5A1 and secretion of T/DHT. Addition of flutamide significantlyreduced secretion of IGFBP1 and prolactin and altered the expression of endometrial receptivity markers. Intracrine biosynthesis of endometrial androgens during decidualization may play a key role in endometrial receptivity and offer a novel target for fertility treatment.",

author = "Gibson, {Douglas A} and Ioannis Simitsidellis and Fiona Cousins and Critchley, {Hilary O. D.} and Saunders, {Philippa T. K.}",

year = "2016",

month = jan,

day = "28",

doi = "10.1038/srep19970",

language = "English",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Intracrine androgens enhance decidualization and modulate expression of human endometrial receptivity genes

AU - Gibson, Douglas A

AU - Simitsidellis, Ioannis

AU - Cousins, Fiona

AU - Critchley, Hilary O. D.

AU - Saunders, Philippa T. K.

PY - 2016/1/28

Y1 - 2016/1/28

N2 - The endometrium is a complex, steroid-dependent tissue that undergoes dynamic cyclical remodelling. Transformation of stromal fibroblasts (ESC) into specialised secretory cells (decidualization) is fundamental to the establishment of a receptive endometrial microenvironment which can support and maintain pregnancy. Androgen receptors (AR) are present in ESC; in other tissues local metabolism of ovarian and adrenal-derived androgens regulate AR-dependent gene expression. We hypothesised that altered expression/activity of androgen biosynthetic enzymes would regulate tissue availability of bioactive androgens and the process of decidualization. Primary human ESC were treated in vitro for1–8 days with progesterone and cAMP (decidualized) in the presence or absence of the AR antagonist flutamide. Time and treatment-dependent changes in genes essential for a) intra-tissue biosynthesis of androgens (5α-reductase/SRD5A1, aldo-keto reductase family 1 member C3/AKR1C3), b)establishment of endometrial decidualization (IGFBP1, prolactin) and c) endometrial receptivity (SPP1, MAOA, EDNRB) were measured. Decidualization of ESC resulted in significant time-dependent changes in expression of AKR1C3 and SRD5A1 and secretion of T/DHT. Addition of flutamide significantlyreduced secretion of IGFBP1 and prolactin and altered the expression of endometrial receptivity markers. Intracrine biosynthesis of endometrial androgens during decidualization may play a key role in endometrial receptivity and offer a novel target for fertility treatment.

AB - The endometrium is a complex, steroid-dependent tissue that undergoes dynamic cyclical remodelling. Transformation of stromal fibroblasts (ESC) into specialised secretory cells (decidualization) is fundamental to the establishment of a receptive endometrial microenvironment which can support and maintain pregnancy. Androgen receptors (AR) are present in ESC; in other tissues local metabolism of ovarian and adrenal-derived androgens regulate AR-dependent gene expression. We hypothesised that altered expression/activity of androgen biosynthetic enzymes would regulate tissue availability of bioactive androgens and the process of decidualization. Primary human ESC were treated in vitro for1–8 days with progesterone and cAMP (decidualized) in the presence or absence of the AR antagonist flutamide. Time and treatment-dependent changes in genes essential for a) intra-tissue biosynthesis of androgens (5α-reductase/SRD5A1, aldo-keto reductase family 1 member C3/AKR1C3), b)establishment of endometrial decidualization (IGFBP1, prolactin) and c) endometrial receptivity (SPP1, MAOA, EDNRB) were measured. Decidualization of ESC resulted in significant time-dependent changes in expression of AKR1C3 and SRD5A1 and secretion of T/DHT. Addition of flutamide significantlyreduced secretion of IGFBP1 and prolactin and altered the expression of endometrial receptivity markers. Intracrine biosynthesis of endometrial androgens during decidualization may play a key role in endometrial receptivity and offer a novel target for fertility treatment.

U2 - 10.1038/srep19970

DO - 10.1038/srep19970

M3 - Article

SN - 2045-2322

JO - Scientific Reports

JF - Scientific Reports

ER -

Intracrine androgens enhance decidualization and modulate expression of human endometrial receptivity genes

Abstract / Description of output

Access to Document

Fingerprint

Projects

Impact of sex steroids on immune and vascular cell function in the reproductive system

Profiles

Philippa Saunders

Cite this