Detection of expressional changes induced by intrauterine growth restriction in the developing rat mammary gland via exploratory pathways analysis.
Intrauterine growth restriction (IUGR) is thought to lead to fetal programming that in turn contributes to developmental changes of many organs postnatally. There is evidence that IUGR is a risk factor for the development of metabolic and cardiovascular disease later in life. A higher incidence of b...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4067350?pdf=render |
| _version_ | 1811206383908945920 |
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| author | Lea Beinder Nina Faehrmann Rainer Wachtveitl Ilona Winterfeld Andrea Hartner Carlos Menendez-Castro Manfred Rauh Matthias Ruebner Hanna Huebner Stephanie C Noegel Helmuth G Doerr Wolfgang Rascher Fabian B Fahlbusch |
| author_facet | Lea Beinder Nina Faehrmann Rainer Wachtveitl Ilona Winterfeld Andrea Hartner Carlos Menendez-Castro Manfred Rauh Matthias Ruebner Hanna Huebner Stephanie C Noegel Helmuth G Doerr Wolfgang Rascher Fabian B Fahlbusch |
| author_sort | Lea Beinder |
| collection | DOAJ |
| description | Intrauterine growth restriction (IUGR) is thought to lead to fetal programming that in turn contributes to developmental changes of many organs postnatally. There is evidence that IUGR is a risk factor for the development of metabolic and cardiovascular disease later in life. A higher incidence of breast cancer was also observed after IUGR. This could be due to changes in mammary gland developmental pathways. We sought to characterise IUGR-induced alterations of the complex pathways of mammary development at the level of the transcriptome in a rat model of IUGR, using pathways analysis bioinformatics.We analysed the mammary glands of Wistar rats with IUGR induced by maternal low protein (LP) diet at the beginning (d21) and the end (d28) of pubertal ductal morphogenesis. Mammary glands of the LP group were smaller in size at d28, however did not show morphologic changes. We identified multiple differentially expressed genes in the mammary gland using Agilent SurePrint arrays at d21 and d28. In silico analysis was carried out using Ingenuity Pathways Analysis. In mammary gland tissue of LP rats at d21 of life a prominent upregulation of WT1 and CDKN1A (p21) expression was observed. Differentially regulated genes were associated with the extracellular regulated kinase (ERK)-1/-2 pathway. Western Blot analysis showed reduced levels of phosphorylated ERK-1/-2 in the mammary glands of the LP group at d21. To identify possible changes in circulating steroid levels, serum LC-Tandem mass-spectrometry was performed. LP rats showed higher serum progesterone levels and an increased corticosterone/dehydrocorticosterone-ratio at d28.Our data obtained from gene array analysis support the hypothesis that IUGR influences pubertal development of the rat mammary gland. We identified prominent differential regulation of genes and pathways for factors regulating cell cycle and growth. Moreover, we detected new pathways which appear to be programmed by IUGR. |
| first_indexed | 2024-04-12T03:46:34Z |
| format | Article |
| id | doaj.art-8f55a86b290e4cc2800daeb3431e8494 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T03:46:34Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-8f55a86b290e4cc2800daeb3431e84942022-12-22T03:49:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0196e10050410.1371/journal.pone.0100504Detection of expressional changes induced by intrauterine growth restriction in the developing rat mammary gland via exploratory pathways analysis.Lea BeinderNina FaehrmannRainer WachtveitlIlona WinterfeldAndrea HartnerCarlos Menendez-CastroManfred RauhMatthias RuebnerHanna HuebnerStephanie C NoegelHelmuth G DoerrWolfgang RascherFabian B FahlbuschIntrauterine growth restriction (IUGR) is thought to lead to fetal programming that in turn contributes to developmental changes of many organs postnatally. There is evidence that IUGR is a risk factor for the development of metabolic and cardiovascular disease later in life. A higher incidence of breast cancer was also observed after IUGR. This could be due to changes in mammary gland developmental pathways. We sought to characterise IUGR-induced alterations of the complex pathways of mammary development at the level of the transcriptome in a rat model of IUGR, using pathways analysis bioinformatics.We analysed the mammary glands of Wistar rats with IUGR induced by maternal low protein (LP) diet at the beginning (d21) and the end (d28) of pubertal ductal morphogenesis. Mammary glands of the LP group were smaller in size at d28, however did not show morphologic changes. We identified multiple differentially expressed genes in the mammary gland using Agilent SurePrint arrays at d21 and d28. In silico analysis was carried out using Ingenuity Pathways Analysis. In mammary gland tissue of LP rats at d21 of life a prominent upregulation of WT1 and CDKN1A (p21) expression was observed. Differentially regulated genes were associated with the extracellular regulated kinase (ERK)-1/-2 pathway. Western Blot analysis showed reduced levels of phosphorylated ERK-1/-2 in the mammary glands of the LP group at d21. To identify possible changes in circulating steroid levels, serum LC-Tandem mass-spectrometry was performed. LP rats showed higher serum progesterone levels and an increased corticosterone/dehydrocorticosterone-ratio at d28.Our data obtained from gene array analysis support the hypothesis that IUGR influences pubertal development of the rat mammary gland. We identified prominent differential regulation of genes and pathways for factors regulating cell cycle and growth. Moreover, we detected new pathways which appear to be programmed by IUGR.http://europepmc.org/articles/PMC4067350?pdf=render |
| spellingShingle | Lea Beinder Nina Faehrmann Rainer Wachtveitl Ilona Winterfeld Andrea Hartner Carlos Menendez-Castro Manfred Rauh Matthias Ruebner Hanna Huebner Stephanie C Noegel Helmuth G Doerr Wolfgang Rascher Fabian B Fahlbusch Detection of expressional changes induced by intrauterine growth restriction in the developing rat mammary gland via exploratory pathways analysis. PLoS ONE |
| title | Detection of expressional changes induced by intrauterine growth restriction in the developing rat mammary gland via exploratory pathways analysis. |
| title_full | Detection of expressional changes induced by intrauterine growth restriction in the developing rat mammary gland via exploratory pathways analysis. |
| title_fullStr | Detection of expressional changes induced by intrauterine growth restriction in the developing rat mammary gland via exploratory pathways analysis. |
| title_full_unstemmed | Detection of expressional changes induced by intrauterine growth restriction in the developing rat mammary gland via exploratory pathways analysis. |
| title_short | Detection of expressional changes induced by intrauterine growth restriction in the developing rat mammary gland via exploratory pathways analysis. |
| title_sort | detection of expressional changes induced by intrauterine growth restriction in the developing rat mammary gland via exploratory pathways analysis |
| url | http://europepmc.org/articles/PMC4067350?pdf=render |
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