Cargando…
In an Ovine Model of Polycystic Ovary Syndrome (PCOS) Prenatal Androgens Suppress Female Fetal Renal Gluconeogenesis
Increased maternal androgen exposure during pregnancy programmes a polycystic ovary syndrome (PCOS)-like condition, with metabolic dysfunction, in adult female offspring. Other in utero exposures associated with the development of insulin resistance, such as intrauterine growth restriction and expos...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492923/ https://www.ncbi.nlm.nih.gov/pubmed/26148093 http://dx.doi.org/10.1371/journal.pone.0132113 |
_version_ | 1782379825988632576 |
---|---|
author | Connolly, Fiona Rae, Michael T. Späth, Katharina Boswell, Lyndsey McNeilly, Alan S. Duncan, W. Colin |
author_facet | Connolly, Fiona Rae, Michael T. Späth, Katharina Boswell, Lyndsey McNeilly, Alan S. Duncan, W. Colin |
author_sort | Connolly, Fiona |
collection | PubMed |
description | Increased maternal androgen exposure during pregnancy programmes a polycystic ovary syndrome (PCOS)-like condition, with metabolic dysfunction, in adult female offspring. Other in utero exposures associated with the development of insulin resistance, such as intrauterine growth restriction and exposure to prenatal glucocorticoids, are associated with altered fetal gluconeogenesis. We therefore aimed to assess the effect of maternal androgenisation on the expression of PEPCK and G6PC in the ovine fetus. Pregnant Scottish Greyface sheep were treated with twice weekly testosterone propionate (TP; 100mg) or vehicle control from day 62 to day102 of gestation. At day 90 and day 112 fetal plasma and liver and kidney tissue was collected for analysis. PEPCK and G6PC expression were analysed by quantitative RT-PCR, immunohistochemistry and western blotting. PEPCK and G6PC were localised to fetal hepatocytes but maternal androgens had no effect on female or male fetuses. PEPCK and G6PC were also localised to the renal tubules and renal PEPCK (P<0.01) and G6PC (P = 0.057) were lower in females after prenatal androgenisation with no change in male fetuses. These tissue and sex specific observations could not be explained by alterations in fetal insulin or cortisol. The sexual dimorphism may be related to the increase in circulating estrogen (P<0.01) and testosterone (P<0.001) in females but not males. The tissue specific effects may be related to the increased expression of ESR1 (P<0.01) and AR (P<0.05) in the kidney when compared to the fetal liver. After discontinuation of maternal androgenisation female fetal kidney PEPCK expression normalised. These data further highlight the fetal and sexual dimorphic effects of maternal androgenisation, an antecedent to adult disease and the plasticity of fetal development. |
format | Online Article Text |
id | pubmed-4492923 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44929232015-07-15 In an Ovine Model of Polycystic Ovary Syndrome (PCOS) Prenatal Androgens Suppress Female Fetal Renal Gluconeogenesis Connolly, Fiona Rae, Michael T. Späth, Katharina Boswell, Lyndsey McNeilly, Alan S. Duncan, W. Colin PLoS One Research Article Increased maternal androgen exposure during pregnancy programmes a polycystic ovary syndrome (PCOS)-like condition, with metabolic dysfunction, in adult female offspring. Other in utero exposures associated with the development of insulin resistance, such as intrauterine growth restriction and exposure to prenatal glucocorticoids, are associated with altered fetal gluconeogenesis. We therefore aimed to assess the effect of maternal androgenisation on the expression of PEPCK and G6PC in the ovine fetus. Pregnant Scottish Greyface sheep were treated with twice weekly testosterone propionate (TP; 100mg) or vehicle control from day 62 to day102 of gestation. At day 90 and day 112 fetal plasma and liver and kidney tissue was collected for analysis. PEPCK and G6PC expression were analysed by quantitative RT-PCR, immunohistochemistry and western blotting. PEPCK and G6PC were localised to fetal hepatocytes but maternal androgens had no effect on female or male fetuses. PEPCK and G6PC were also localised to the renal tubules and renal PEPCK (P<0.01) and G6PC (P = 0.057) were lower in females after prenatal androgenisation with no change in male fetuses. These tissue and sex specific observations could not be explained by alterations in fetal insulin or cortisol. The sexual dimorphism may be related to the increase in circulating estrogen (P<0.01) and testosterone (P<0.001) in females but not males. The tissue specific effects may be related to the increased expression of ESR1 (P<0.01) and AR (P<0.05) in the kidney when compared to the fetal liver. After discontinuation of maternal androgenisation female fetal kidney PEPCK expression normalised. These data further highlight the fetal and sexual dimorphic effects of maternal androgenisation, an antecedent to adult disease and the plasticity of fetal development. Public Library of Science 2015-07-06 /pmc/articles/PMC4492923/ /pubmed/26148093 http://dx.doi.org/10.1371/journal.pone.0132113 Text en © 2015 Connolly 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 Connolly, Fiona Rae, Michael T. Späth, Katharina Boswell, Lyndsey McNeilly, Alan S. Duncan, W. Colin In an Ovine Model of Polycystic Ovary Syndrome (PCOS) Prenatal Androgens Suppress Female Fetal Renal Gluconeogenesis |
title | In an Ovine Model of Polycystic Ovary Syndrome (PCOS) Prenatal Androgens Suppress Female Fetal Renal Gluconeogenesis |
title_full | In an Ovine Model of Polycystic Ovary Syndrome (PCOS) Prenatal Androgens Suppress Female Fetal Renal Gluconeogenesis |
title_fullStr | In an Ovine Model of Polycystic Ovary Syndrome (PCOS) Prenatal Androgens Suppress Female Fetal Renal Gluconeogenesis |
title_full_unstemmed | In an Ovine Model of Polycystic Ovary Syndrome (PCOS) Prenatal Androgens Suppress Female Fetal Renal Gluconeogenesis |
title_short | In an Ovine Model of Polycystic Ovary Syndrome (PCOS) Prenatal Androgens Suppress Female Fetal Renal Gluconeogenesis |
title_sort | in an ovine model of polycystic ovary syndrome (pcos) prenatal androgens suppress female fetal renal gluconeogenesis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492923/ https://www.ncbi.nlm.nih.gov/pubmed/26148093 http://dx.doi.org/10.1371/journal.pone.0132113 |
work_keys_str_mv | AT connollyfiona inanovinemodelofpolycysticovarysyndromepcosprenatalandrogenssuppressfemalefetalrenalgluconeogenesis AT raemichaelt inanovinemodelofpolycysticovarysyndromepcosprenatalandrogenssuppressfemalefetalrenalgluconeogenesis AT spathkatharina inanovinemodelofpolycysticovarysyndromepcosprenatalandrogenssuppressfemalefetalrenalgluconeogenesis AT boswelllyndsey inanovinemodelofpolycysticovarysyndromepcosprenatalandrogenssuppressfemalefetalrenalgluconeogenesis AT mcneillyalans inanovinemodelofpolycysticovarysyndromepcosprenatalandrogenssuppressfemalefetalrenalgluconeogenesis AT duncanwcolin inanovinemodelofpolycysticovarysyndromepcosprenatalandrogenssuppressfemalefetalrenalgluconeogenesis |