2.50
Hdl Handle:
http://hdl.handle.net/10755/157445
Type:
Presentation
Title:
EPIGENETIC PATTERNS IN PLACENTAL PROGRAMMING OF PREECLAMPSIA
Abstract:
EPIGENETIC PATTERNS IN PLACENTAL PROGRAMMING OF PREECLAMPSIA
Conference Sponsor:Western Institute of Nursing
Conference Year:2010
Author:Anderson, Cindy M., PhD, RN, WHNP-BC
P.I. Institution Name:University of North Dakota
Title:Associate Professor
Contact Address:400 Oxford Street Stop 9025, Grand Forks, ND, 58202-9025, USA
Co-Authors:Eric Uthus
PURPOSES/AIMS: Preeclampsia, a form of pregnancy-induced hypertension, affects 8-10% of women in the United States. The acute effects of preeclampsia are the result of placental insufficiency leading to pregnancy-induced hypertension in the second half of pregnancy. Long-term consequences of preeclampsia include subsequent development of maternal primary hypertension and hypertension (primary and pregnancy-induced) in offspring. As DNA methylation patterns are established during fetal life and are influenced by maternal nutrition, this study focused on investigation of maternal nutritional status and placental programming through epigenetic alterations in DNA methylation as a plausible explanation of the heritable development of hypertension resulting from maternal preeclampsia.
RATIONALE/CONCEPTUAL BASIS/BACKGROUND: In a pilot study of 46 nulliparous women, we investigated the association between maternal first trimester nutritional status and the subsequent development of preeclampsia. No significant differences in macro- and micronutrient dietary intake or serum status were identified, with the exception of maternal vitamin D. All women reported supplement use containing the recommended vitamin D intake of 400 IU, with dietary intake providing an additional 259-342 IU/day. Vitamin D status was adequate in only 30% of the sample, with the remaining 70% of participants either insufficient (44%) or deficient (26%). The incidence of preeclampsia was 23.9%, far exceeding national norms. As the placenta serves as a significant source of vitamin D production and utilization, we investigated the DNA methylation status of placental genes involved in vitamin D signaling.
METHODS: Genome-wide DNA methylation patterns were determined in placental tissue from women with normotensive pregnancy (control) and preeclampsia (n=3/group), targeting genes producing proteins used in vitamin D signaling. Samples were labeled and co-hybridized to Human DNA Methylation 2.1M microarrays (NimbleGen). Raw data were analyzed using NimbleScan software producing signal ratio values and estimating the significance of enrichment. Promoters and genes with DNA methylation differences (hypo or hyper methylated) in experimental vs. control samples were identified.
RESULTS: Vitamin D-mediated gene transcription is initiated when the active form of vitamin D (1,25-dihydroxyvitamin D3 [1,25[OH]2D]) binds with the vitamin D receptor (VDR) which forms a heterodimer with the retinoid X receptor (RXR). The complex binds to the vitamin D responsive element (VDRE) on a vitamin D-responsive gene, leading to transcription of protein products. The promoter region for the VDR (gene id 7421) which encodes the nuclear hormone receptor for vitamin D3 was methylated near the transcription start site in placentas from women with preeclampsia, suggesting that expression of this gene is down regulated in preeclampsia. Retinoid X receptor alpha (RXR alpha, gene id 6256) which is a significant contributor to VDR mediated gene expression was also found to be methylated in the promoter region in placentas from women with preeclampsia compared to those unmethylated in normal pregnancy.
IMPLICATIONS: Vitamin D insufficiency in pregnancy is associated with increased blood pressure and risk for preeclampsia, leading to increased cardiovascular risk in mothers and children. Placental DNA hyper methylation in the VDR and RXR may reduce vitamin D binding and gene transcription thereby reducing utilization during pregnancy and programming the fetal cardiovascular system for future risk of preeclampsia and hypertension.
Repository Posting Date:
26-Oct-2011
Date of Publication:
17-Oct-2011
Sponsors:
Western Institute of Nursing

Full metadata record

DC FieldValue Language
dc.typePresentationen_GB
dc.titleEPIGENETIC PATTERNS IN PLACENTAL PROGRAMMING OF PREECLAMPSIAen_GB
dc.identifier.urihttp://hdl.handle.net/10755/157445-
dc.description.abstract<table><tr><td colspan="2" class="item-title">EPIGENETIC PATTERNS IN PLACENTAL PROGRAMMING OF PREECLAMPSIA</td></tr><tr class="item-sponsor"><td class="label">Conference Sponsor:</td><td class="value">Western Institute of Nursing</td></tr><tr class="item-year"><td class="label">Conference Year:</td><td class="value">2010</td></tr><tr class="item-author"><td class="label">Author:</td><td class="value">Anderson, Cindy M., PhD, RN, WHNP-BC</td></tr><tr class="item-institute"><td class="label">P.I. Institution Name:</td><td class="value">University of North Dakota</td></tr><tr class="item-author-title"><td class="label">Title:</td><td class="value">Associate Professor</td></tr><tr class="item-address"><td class="label">Contact Address:</td><td class="value">400 Oxford Street Stop 9025, Grand Forks, ND, 58202-9025, USA</td></tr><tr class="item-email"><td class="label">Email:</td><td class="value">cindyanderson@mail.und.edu</td></tr><tr class="item-co-authors"><td class="label">Co-Authors:</td><td class="value">Eric Uthus</td></tr><tr><td colspan="2" class="item-abstract">PURPOSES/AIMS: Preeclampsia, a form of pregnancy-induced hypertension, affects 8-10% of women in the United States. The acute effects of preeclampsia are the result of placental insufficiency leading to pregnancy-induced hypertension in the second half of pregnancy. Long-term consequences of preeclampsia include subsequent development of maternal primary hypertension and hypertension (primary and pregnancy-induced) in offspring. As DNA methylation patterns are established during fetal life and are influenced by maternal nutrition, this study focused on investigation of maternal nutritional status and placental programming through epigenetic alterations in DNA methylation as a plausible explanation of the heritable development of hypertension resulting from maternal preeclampsia. <br/>RATIONALE/CONCEPTUAL BASIS/BACKGROUND: In a pilot study of 46 nulliparous women, we investigated the association between maternal first trimester nutritional status and the subsequent development of preeclampsia. No significant differences in macro- and micronutrient dietary intake or serum status were identified, with the exception of maternal vitamin D. All women reported supplement use containing the recommended vitamin D intake of 400 IU, with dietary intake providing an additional 259-342 IU/day. Vitamin D status was adequate in only 30% of the sample, with the remaining 70% of participants either insufficient (44%) or deficient (26%). The incidence of preeclampsia was 23.9%, far exceeding national norms. As the placenta serves as a significant source of vitamin D production and utilization, we investigated the DNA methylation status of placental genes involved in vitamin D signaling.<br/>METHODS: Genome-wide DNA methylation patterns were determined in placental tissue from women with normotensive pregnancy (control) and preeclampsia (n=3/group), targeting genes producing proteins used in vitamin D signaling. Samples were labeled and co-hybridized to Human DNA Methylation 2.1M microarrays (NimbleGen). Raw data were analyzed using NimbleScan software producing signal ratio values and estimating the significance of enrichment. Promoters and genes with DNA methylation differences (hypo or hyper methylated) in experimental vs. control samples were identified.<br/>RESULTS: Vitamin D-mediated gene transcription is initiated when the active form of vitamin D (1,25-dihydroxyvitamin D3 [1,25[OH]2D]) binds with the vitamin D receptor (VDR) which forms a heterodimer with the retinoid X receptor (RXR). The complex binds to the vitamin D responsive element (VDRE) on a vitamin D-responsive gene, leading to transcription of protein products. The promoter region for the VDR (gene id 7421) which encodes the nuclear hormone receptor for vitamin D3 was methylated near the transcription start site in placentas from women with preeclampsia, suggesting that expression of this gene is down regulated in preeclampsia. Retinoid X receptor alpha (RXR alpha, gene id 6256) which is a significant contributor to VDR mediated gene expression was also found to be methylated in the promoter region in placentas from women with preeclampsia compared to those unmethylated in normal pregnancy.<br/>IMPLICATIONS: Vitamin D insufficiency in pregnancy is associated with increased blood pressure and risk for preeclampsia, leading to increased cardiovascular risk in mothers and children. Placental DNA hyper methylation in the VDR and RXR may reduce vitamin D binding and gene transcription thereby reducing utilization during pregnancy and programming the fetal cardiovascular system for future risk of preeclampsia and hypertension.<br/></td></tr></table>en_GB
dc.date.available2011-10-26T19:52:48Z-
dc.date.issued2011-10-17en_GB
dc.date.accessioned2011-10-26T19:52:48Z-
dc.description.sponsorshipWestern Institute of Nursingen_GB
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