aP2-Cre-mediated inactivation of estrogen receptor alpha causes hydrometra.

In this study we describe the reproductive phenotypes of a novel mouse model in which Cre-mediated deletion of ERα is regulated by the aP2 (fatty acid binding protein 4) promoter. ERα-floxed mice were crossed with transgenic mice expressing Cre-recombinase under the control of the aP2 promoter to ge...

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Autores principales:	Per Antonson, Marko Matic, Neil Portwood, Raoul V Kuiper, Galyna Bryzgalova, Hui Gao, Sara H Windahl, Patricia Humire, Claes Ohlsson, Per-Olof Berggren, Jan-Åke Gustafsson, Karin Dahlman-Wright
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ed88f335c13244e8ac3c98cce9caa6b2
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spelling	oai:doaj.org-article:ed88f335c13244e8ac3c98cce9caa6b22021-11-18T08:38:21ZaP2-Cre-mediated inactivation of estrogen receptor alpha causes hydrometra.1932-620310.1371/journal.pone.0085581https://doaj.org/article/ed88f335c13244e8ac3c98cce9caa6b22014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24416430/?tool=EBIhttps://doaj.org/toc/1932-6203In this study we describe the reproductive phenotypes of a novel mouse model in which Cre-mediated deletion of ERα is regulated by the aP2 (fatty acid binding protein 4) promoter. ERα-floxed mice were crossed with transgenic mice expressing Cre-recombinase under the control of the aP2 promoter to generate aP2-Cre/ERα(flox/flox) mice. As expected, ERα mRNA levels were reduced in adipose tissue, but in addition we also detected an 80% reduction of ERα levels in the hypothalamus of aP2-Cre/ERα(flox/flox) mice. Phenotypic analysis revealed that aP2-Cre/ERα(flox/flox) female mice were infertile. In line with this, aP2-Cre/ERα(flox/flox) female mice did not cycle and presented 3.8-fold elevated estrogen levels. That elevated estrogen levels were associated with increased estrogen signaling was evidenced by increased mRNA levels of the estrogen-regulated genes lactoferrin and aquaporin 5 in the uterus. Furthermore, aP2-Cre/ERα(flox/flox) female mice showed an accumulation of intra-uterine fluid, hydrometra, without overt indications for causative anatomical anomalies. However, the vagina and cervix displayed advanced keratosis with abnormal quantities of accumulating squamous epithelial cells suggesting functional obstruction by keratin plugs. Importantly, treatment of aP2-Cre/ERα(flox/flox) mice with the aromatase inhibitor Letrozole caused regression of the hydrometra phenotype linking increased estrogen levels to the observed phenotype. We propose that in aP2-Cre/ERα(flox/flox) mice, increased serum estrogen levels cause over-stimulation in the uterus and genital tracts resulting in hydrometra and vaginal obstruction.Per AntonsonMarko MaticNeil PortwoodRaoul V KuiperGalyna BryzgalovaHui GaoSara H WindahlPatricia HumireClaes OhlssonPer-Olof BerggrenJan-Åke GustafssonKarin Dahlman-WrightPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e85581 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Per Antonson Marko Matic Neil Portwood Raoul V Kuiper Galyna Bryzgalova Hui Gao Sara H Windahl Patricia Humire Claes Ohlsson Per-Olof Berggren Jan-Åke Gustafsson Karin Dahlman-Wright aP2-Cre-mediated inactivation of estrogen receptor alpha causes hydrometra.
description	In this study we describe the reproductive phenotypes of a novel mouse model in which Cre-mediated deletion of ERα is regulated by the aP2 (fatty acid binding protein 4) promoter. ERα-floxed mice were crossed with transgenic mice expressing Cre-recombinase under the control of the aP2 promoter to generate aP2-Cre/ERα(flox/flox) mice. As expected, ERα mRNA levels were reduced in adipose tissue, but in addition we also detected an 80% reduction of ERα levels in the hypothalamus of aP2-Cre/ERα(flox/flox) mice. Phenotypic analysis revealed that aP2-Cre/ERα(flox/flox) female mice were infertile. In line with this, aP2-Cre/ERα(flox/flox) female mice did not cycle and presented 3.8-fold elevated estrogen levels. That elevated estrogen levels were associated with increased estrogen signaling was evidenced by increased mRNA levels of the estrogen-regulated genes lactoferrin and aquaporin 5 in the uterus. Furthermore, aP2-Cre/ERα(flox/flox) female mice showed an accumulation of intra-uterine fluid, hydrometra, without overt indications for causative anatomical anomalies. However, the vagina and cervix displayed advanced keratosis with abnormal quantities of accumulating squamous epithelial cells suggesting functional obstruction by keratin plugs. Importantly, treatment of aP2-Cre/ERα(flox/flox) mice with the aromatase inhibitor Letrozole caused regression of the hydrometra phenotype linking increased estrogen levels to the observed phenotype. We propose that in aP2-Cre/ERα(flox/flox) mice, increased serum estrogen levels cause over-stimulation in the uterus and genital tracts resulting in hydrometra and vaginal obstruction.
format	article
author	Per Antonson Marko Matic Neil Portwood Raoul V Kuiper Galyna Bryzgalova Hui Gao Sara H Windahl Patricia Humire Claes Ohlsson Per-Olof Berggren Jan-Åke Gustafsson Karin Dahlman-Wright
author_facet	Per Antonson Marko Matic Neil Portwood Raoul V Kuiper Galyna Bryzgalova Hui Gao Sara H Windahl Patricia Humire Claes Ohlsson Per-Olof Berggren Jan-Åke Gustafsson Karin Dahlman-Wright
author_sort	Per Antonson
title	aP2-Cre-mediated inactivation of estrogen receptor alpha causes hydrometra.
title_short	aP2-Cre-mediated inactivation of estrogen receptor alpha causes hydrometra.
title_full	aP2-Cre-mediated inactivation of estrogen receptor alpha causes hydrometra.
title_fullStr	aP2-Cre-mediated inactivation of estrogen receptor alpha causes hydrometra.
title_full_unstemmed	aP2-Cre-mediated inactivation of estrogen receptor alpha causes hydrometra.
title_sort	ap2-cre-mediated inactivation of estrogen receptor alpha causes hydrometra.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/ed88f335c13244e8ac3c98cce9caa6b2
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aP2-Cre-mediated inactivation of estrogen receptor alpha causes hydrometra.

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