Androgen Receptor and Histone Lysine Demethylases in Ovine Placenta

Sex steroid hormones regulate developmental programming in many tissues, including programming gene expression during prenatal development. While estradiol is known to regulate placentation, little is known about the role of testosterone and androgen signaling in placental development despite the fa...

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Autores principales: Cleys, Ellane R., Halleran, Jennifer L., Enriquez, Vanessa A., da Silveira, Juliano C., West, Rachel C., Winger, Quinton A., Anthony, Russell V., Bruemmer, Jason E., Clay, Colin M., Bouma, Gerrit J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326353/
https://www.ncbi.nlm.nih.gov/pubmed/25675430
http://dx.doi.org/10.1371/journal.pone.0117472
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author Cleys, Ellane R.
Halleran, Jennifer L.
Enriquez, Vanessa A.
da Silveira, Juliano C.
West, Rachel C.
Winger, Quinton A.
Anthony, Russell V.
Bruemmer, Jason E.
Clay, Colin M.
Bouma, Gerrit J.
author_facet Cleys, Ellane R.
Halleran, Jennifer L.
Enriquez, Vanessa A.
da Silveira, Juliano C.
West, Rachel C.
Winger, Quinton A.
Anthony, Russell V.
Bruemmer, Jason E.
Clay, Colin M.
Bouma, Gerrit J.
author_sort Cleys, Ellane R.
collection PubMed
description Sex steroid hormones regulate developmental programming in many tissues, including programming gene expression during prenatal development. While estradiol is known to regulate placentation, little is known about the role of testosterone and androgen signaling in placental development despite the fact that testosterone rises in maternal circulation during pregnancy and in placenta-induced pregnancy disorders. We investigated the role of testosterone in placental gene expression, and focused on androgen receptor (AR). Prenatal androgenization decreased global DNA methylation in gestational day 90 placentomes, and increased placental expression of AR as well as genes involved in epigenetic regulation, angiogenesis, and growth. As AR complexes with histone lysine demethylases (KDMs) to regulate AR target genes in human cancers, we also investigated if the same mechanism is present in the ovine placenta. AR co-immunoprecipitated with KDM1A and KDM4D in sheep placentomes, and AR-KDM1A complexes were recruited to a half-site for androgen response element (ARE) in the promoter region of VEGFA. Androgenized ewes also had increased cotyledonary VEGFA. Finally, in human first trimester placental samples KDM1A and KDM4D immunolocalized to the syncytiotrophoblast, with nuclear KDM1A and KDM4D immunostaining also present in the villous stroma. In conclusion, placental androgen signaling, possibly through AR-KDM complex recruitment to AREs, regulates placental VEGFA expression. AR and KDMs are also present in first trimester human placenta. Androgens appear to be an important regulator of trophoblast differentiation and placental development, and aberrant androgen signaling may contribute to the development of placental disorders.
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spelling pubmed-43263532015-02-24 Androgen Receptor and Histone Lysine Demethylases in Ovine Placenta Cleys, Ellane R. Halleran, Jennifer L. Enriquez, Vanessa A. da Silveira, Juliano C. West, Rachel C. Winger, Quinton A. Anthony, Russell V. Bruemmer, Jason E. Clay, Colin M. Bouma, Gerrit J. PLoS One Research Article Sex steroid hormones regulate developmental programming in many tissues, including programming gene expression during prenatal development. While estradiol is known to regulate placentation, little is known about the role of testosterone and androgen signaling in placental development despite the fact that testosterone rises in maternal circulation during pregnancy and in placenta-induced pregnancy disorders. We investigated the role of testosterone in placental gene expression, and focused on androgen receptor (AR). Prenatal androgenization decreased global DNA methylation in gestational day 90 placentomes, and increased placental expression of AR as well as genes involved in epigenetic regulation, angiogenesis, and growth. As AR complexes with histone lysine demethylases (KDMs) to regulate AR target genes in human cancers, we also investigated if the same mechanism is present in the ovine placenta. AR co-immunoprecipitated with KDM1A and KDM4D in sheep placentomes, and AR-KDM1A complexes were recruited to a half-site for androgen response element (ARE) in the promoter region of VEGFA. Androgenized ewes also had increased cotyledonary VEGFA. Finally, in human first trimester placental samples KDM1A and KDM4D immunolocalized to the syncytiotrophoblast, with nuclear KDM1A and KDM4D immunostaining also present in the villous stroma. In conclusion, placental androgen signaling, possibly through AR-KDM complex recruitment to AREs, regulates placental VEGFA expression. AR and KDMs are also present in first trimester human placenta. Androgens appear to be an important regulator of trophoblast differentiation and placental development, and aberrant androgen signaling may contribute to the development of placental disorders. Public Library of Science 2015-02-12 /pmc/articles/PMC4326353/ /pubmed/25675430 http://dx.doi.org/10.1371/journal.pone.0117472 Text en © 2015 Cleys et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Cleys, Ellane R.
Halleran, Jennifer L.
Enriquez, Vanessa A.
da Silveira, Juliano C.
West, Rachel C.
Winger, Quinton A.
Anthony, Russell V.
Bruemmer, Jason E.
Clay, Colin M.
Bouma, Gerrit J.
Androgen Receptor and Histone Lysine Demethylases in Ovine Placenta
title Androgen Receptor and Histone Lysine Demethylases in Ovine Placenta
title_full Androgen Receptor and Histone Lysine Demethylases in Ovine Placenta
title_fullStr Androgen Receptor and Histone Lysine Demethylases in Ovine Placenta
title_full_unstemmed Androgen Receptor and Histone Lysine Demethylases in Ovine Placenta
title_short Androgen Receptor and Histone Lysine Demethylases in Ovine Placenta
title_sort androgen receptor and histone lysine demethylases in ovine placenta
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326353/
https://www.ncbi.nlm.nih.gov/pubmed/25675430
http://dx.doi.org/10.1371/journal.pone.0117472
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