The in utero programming effect of increased maternal androgens and a direct fetal intervention on liver and metabolic function in adult sheep.

Epigenetic changes in response to external stimuli are fast emerging as common underlying causes for the pre-disposition to adult disease. Prenatal androgenization is one such model that results in reproductive and metabolic features that are present in conditions such as polycystic ovary syndrome (...

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Autores principales:	Kirsten Hogg, Charlotte Wood, Alan S McNeilly, W Colin Duncan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a497d4ab59ff47b5bf2a68e477119ae3
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spelling	oai:doaj.org-article:a497d4ab59ff47b5bf2a68e477119ae32021-11-04T06:08:35ZThe in utero programming effect of increased maternal androgens and a direct fetal intervention on liver and metabolic function in adult sheep.1932-620310.1371/journal.pone.0024877https://doaj.org/article/a497d4ab59ff47b5bf2a68e477119ae32011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21935484/?tool=EBIhttps://doaj.org/toc/1932-6203Epigenetic changes in response to external stimuli are fast emerging as common underlying causes for the pre-disposition to adult disease. Prenatal androgenization is one such model that results in reproductive and metabolic features that are present in conditions such as polycystic ovary syndrome (PCOS). We examined the effect of prenatal androgens on liver function and metabolism of adult sheep. As non-alcoholic fatty liver disease is increased in PCOS we hypothesized that this, and other important liver pathways including metabolic function, insulin-like growth factor (IGF) and steroid receptivity, would be affected. Pregnant ewes received vehicle control (C; n = 5) or testosterone propionate (TP; n = 9) twice weekly (100 mg; i.m) from d62-102 (gestation 147 days). In a novel treatment paradigm, a second cohort received a direct C (n = 4) or TP (20 mg; n = 7) fetal injection at d62 and d82. In adults, maternal TP exposure resulted in increased insulin secretion to glucose load (P<0.05) and the histological presence of fatty liver (P<0.05) independent of central obesity. Additionally, hepatic androgen receptor (AR; P<0.05), glucocorticoid receptor (GR; P<0.05), UDP- glucose ceramide glucosyltransferase (UGCG; P<0.05) and IGF1 (P<0.01) expression were upregulated. The direct fetal intervention (C and TP) led to early fatty liver changes in all animals without differential changes in insulin secretion. Furthermore, hepatic phosphoenolpyruvate carboxykinase (PEPCK) was up-regulated in the fetal controls (P<0.05) and this was opposed by fetal TP (P<0.05). Hepatic estrogen receptor (ERα; P<0.05) and mitogen activated protein kinase kinase 4 (MAP2K4; P<0.05) were increased following fetal TP exposure. Adult liver metabolism and signaling can be altered by early exposure to sex steroids implicating epigenetic regulation of metabolic disturbances that are common in PCOS.Kirsten HoggCharlotte WoodAlan S McNeillyW Colin DuncanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 9, p e24877 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kirsten Hogg Charlotte Wood Alan S McNeilly W Colin Duncan The in utero programming effect of increased maternal androgens and a direct fetal intervention on liver and metabolic function in adult sheep.
description	Epigenetic changes in response to external stimuli are fast emerging as common underlying causes for the pre-disposition to adult disease. Prenatal androgenization is one such model that results in reproductive and metabolic features that are present in conditions such as polycystic ovary syndrome (PCOS). We examined the effect of prenatal androgens on liver function and metabolism of adult sheep. As non-alcoholic fatty liver disease is increased in PCOS we hypothesized that this, and other important liver pathways including metabolic function, insulin-like growth factor (IGF) and steroid receptivity, would be affected. Pregnant ewes received vehicle control (C; n = 5) or testosterone propionate (TP; n = 9) twice weekly (100 mg; i.m) from d62-102 (gestation 147 days). In a novel treatment paradigm, a second cohort received a direct C (n = 4) or TP (20 mg; n = 7) fetal injection at d62 and d82. In adults, maternal TP exposure resulted in increased insulin secretion to glucose load (P<0.05) and the histological presence of fatty liver (P<0.05) independent of central obesity. Additionally, hepatic androgen receptor (AR; P<0.05), glucocorticoid receptor (GR; P<0.05), UDP- glucose ceramide glucosyltransferase (UGCG; P<0.05) and IGF1 (P<0.01) expression were upregulated. The direct fetal intervention (C and TP) led to early fatty liver changes in all animals without differential changes in insulin secretion. Furthermore, hepatic phosphoenolpyruvate carboxykinase (PEPCK) was up-regulated in the fetal controls (P<0.05) and this was opposed by fetal TP (P<0.05). Hepatic estrogen receptor (ERα; P<0.05) and mitogen activated protein kinase kinase 4 (MAP2K4; P<0.05) were increased following fetal TP exposure. Adult liver metabolism and signaling can be altered by early exposure to sex steroids implicating epigenetic regulation of metabolic disturbances that are common in PCOS.
format	article
author	Kirsten Hogg Charlotte Wood Alan S McNeilly W Colin Duncan
author_facet	Kirsten Hogg Charlotte Wood Alan S McNeilly W Colin Duncan
author_sort	Kirsten Hogg
title	The in utero programming effect of increased maternal androgens and a direct fetal intervention on liver and metabolic function in adult sheep.
title_short	The in utero programming effect of increased maternal androgens and a direct fetal intervention on liver and metabolic function in adult sheep.
title_full	The in utero programming effect of increased maternal androgens and a direct fetal intervention on liver and metabolic function in adult sheep.
title_fullStr	The in utero programming effect of increased maternal androgens and a direct fetal intervention on liver and metabolic function in adult sheep.
title_full_unstemmed	The in utero programming effect of increased maternal androgens and a direct fetal intervention on liver and metabolic function in adult sheep.
title_sort	in utero programming effect of increased maternal androgens and a direct fetal intervention on liver and metabolic function in adult sheep.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/a497d4ab59ff47b5bf2a68e477119ae3
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The in utero programming effect of increased maternal androgens and a direct fetal intervention on liver and metabolic function in adult sheep.

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