Jens Randel Nyengaard

Fetal Renal DNA Methylation and Developmental Programming of Stress-Induced Hypertension in Growth-Restricted Male Mice

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

Fetal Renal DNA Methylation and Developmental Programming of Stress-Induced Hypertension in Growth-Restricted Male Mice. / DuPriest, Elizabeth; Hebert, Jessica; Morita, Mayu et al.

In: Reproductive Sciences, Vol. 27, No. 5, 2020, p. 1110-1120.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

DuPriest, E, Hebert, J, Morita, M, Marek, N, Meserve, EEK, Andeen, N, Houseman, EA, Qi, Y, Alwasel, S, Nyengaard, J & Morgan, T 2020, 'Fetal Renal DNA Methylation and Developmental Programming of Stress-Induced Hypertension in Growth-Restricted Male Mice', Reproductive Sciences, vol. 27, no. 5, pp. 1110-1120. https://doi.org/10.1007/s43032-019-00121-5

APA

DuPriest, E., Hebert, J., Morita, M., Marek, N., Meserve, E. E. K., Andeen, N., Houseman, E. A., Qi, Y., Alwasel, S., Nyengaard, J., & Morgan, T. (2020). Fetal Renal DNA Methylation and Developmental Programming of Stress-Induced Hypertension in Growth-Restricted Male Mice. Reproductive Sciences, 27(5), 1110-1120. https://doi.org/10.1007/s43032-019-00121-5

CBE

DuPriest E, Hebert J, Morita M, Marek N, Meserve EEK, Andeen N, Houseman EA, Qi Y, Alwasel S, Nyengaard J, et al. 2020. Fetal Renal DNA Methylation and Developmental Programming of Stress-Induced Hypertension in Growth-Restricted Male Mice. Reproductive Sciences. 27(5):1110-1120. https://doi.org/10.1007/s43032-019-00121-5

MLA

Vancouver

DuPriest E, Hebert J, Morita M, Marek N, Meserve EEK, Andeen N et al. Fetal Renal DNA Methylation and Developmental Programming of Stress-Induced Hypertension in Growth-Restricted Male Mice. Reproductive Sciences. 2020;27(5):1110-1120. https://doi.org/10.1007/s43032-019-00121-5

Author

DuPriest, Elizabeth ; Hebert, Jessica ; Morita, Mayu et al. / Fetal Renal DNA Methylation and Developmental Programming of Stress-Induced Hypertension in Growth-Restricted Male Mice. In: Reproductive Sciences. 2020 ; Vol. 27, No. 5. pp. 1110-1120.

Bibtex

@article{8cf2b87a810844b3a257929802f6d555,
title = "Fetal Renal DNA Methylation and Developmental Programming of Stress-Induced Hypertension in Growth-Restricted Male Mice",
abstract = "Fetal growth restriction (FGR) is associated with developmental programming of adult onset hypertension, which may be related to differences in nephron development. Prior studies showed that maternal nutrient restriction is associated with reduced nephrogenesis in rodents, especially in male progeny. We hypothesized that maternal genetic risk for FGR may similarly affect fetal kidney development, leading to adult onset hypertension. We employed an angiotensinogen (AGT) gene titration transgenic (TG) construct with 3 copies of the mouse AGT gene that mimics a common human genotype (AGT A[-6]G) associated with FGR. We investigated whether FGR in 2-copy (wild type, [WT]) progeny from 3-copy TG dams leads to developmental programming differences in kidney development and adult blood pressure compared with age- and sex-matched controls. Progeny were tested in the late fetal period (e17.5), neonatal period (2 weeks of age), and as young adults (12 weeks). We measured weights, tested for renal oxidative stress, compared renal DNA methylation profiles, counted the number of glomeruli, and measured adult blood pressure ± stress. Progeny from TG dams were growth restricted with evidence of renal oxidative stress, males showed fetal renal DNA hypermethylation, they had fewer glomeruli, and they developed stress-induced hypertension as adults. Their female siblings did not share this pathology and instead resembled progeny from WT dams. Surprisingly, glomerular counts in the neonatal period were not different between sexes or maternal genotypes. In turn, we suspect that differences in fetal renal DNA methylation may affect the long-term viability of glomeruli, rather than reducing nephrogenesis.",
keywords = "Angiotensinogen, Developmental programming, DNA methylation, Hypertension, Nephrogenesis",
author = "Elizabeth DuPriest and Jessica Hebert and Mayu Morita and Nicole Marek and Meserve, {Emily E.K.} and Nicole Andeen and Houseman, {E. Andres} and Yue Qi and Saleh Alwasel and Jens Nyengaard and Terry Morgan",
year = "2020",
doi = "10.1007/s43032-019-00121-5",
language = "English",
volume = "27",
pages = "1110--1120",
journal = "Reproductive Sciences",
issn = "1933-7191",
publisher = "Sage Publications, Inc.",
number = "5",

}

RIS

TY - JOUR

T1 - Fetal Renal DNA Methylation and Developmental Programming of Stress-Induced Hypertension in Growth-Restricted Male Mice

AU - DuPriest, Elizabeth

AU - Hebert, Jessica

AU - Morita, Mayu

AU - Marek, Nicole

AU - Meserve, Emily E.K.

AU - Andeen, Nicole

AU - Houseman, E. Andres

AU - Qi, Yue

AU - Alwasel, Saleh

AU - Nyengaard, Jens

AU - Morgan, Terry

PY - 2020

Y1 - 2020

N2 - Fetal growth restriction (FGR) is associated with developmental programming of adult onset hypertension, which may be related to differences in nephron development. Prior studies showed that maternal nutrient restriction is associated with reduced nephrogenesis in rodents, especially in male progeny. We hypothesized that maternal genetic risk for FGR may similarly affect fetal kidney development, leading to adult onset hypertension. We employed an angiotensinogen (AGT) gene titration transgenic (TG) construct with 3 copies of the mouse AGT gene that mimics a common human genotype (AGT A[-6]G) associated with FGR. We investigated whether FGR in 2-copy (wild type, [WT]) progeny from 3-copy TG dams leads to developmental programming differences in kidney development and adult blood pressure compared with age- and sex-matched controls. Progeny were tested in the late fetal period (e17.5), neonatal period (2 weeks of age), and as young adults (12 weeks). We measured weights, tested for renal oxidative stress, compared renal DNA methylation profiles, counted the number of glomeruli, and measured adult blood pressure ± stress. Progeny from TG dams were growth restricted with evidence of renal oxidative stress, males showed fetal renal DNA hypermethylation, they had fewer glomeruli, and they developed stress-induced hypertension as adults. Their female siblings did not share this pathology and instead resembled progeny from WT dams. Surprisingly, glomerular counts in the neonatal period were not different between sexes or maternal genotypes. In turn, we suspect that differences in fetal renal DNA methylation may affect the long-term viability of glomeruli, rather than reducing nephrogenesis.

AB - Fetal growth restriction (FGR) is associated with developmental programming of adult onset hypertension, which may be related to differences in nephron development. Prior studies showed that maternal nutrient restriction is associated with reduced nephrogenesis in rodents, especially in male progeny. We hypothesized that maternal genetic risk for FGR may similarly affect fetal kidney development, leading to adult onset hypertension. We employed an angiotensinogen (AGT) gene titration transgenic (TG) construct with 3 copies of the mouse AGT gene that mimics a common human genotype (AGT A[-6]G) associated with FGR. We investigated whether FGR in 2-copy (wild type, [WT]) progeny from 3-copy TG dams leads to developmental programming differences in kidney development and adult blood pressure compared with age- and sex-matched controls. Progeny were tested in the late fetal period (e17.5), neonatal period (2 weeks of age), and as young adults (12 weeks). We measured weights, tested for renal oxidative stress, compared renal DNA methylation profiles, counted the number of glomeruli, and measured adult blood pressure ± stress. Progeny from TG dams were growth restricted with evidence of renal oxidative stress, males showed fetal renal DNA hypermethylation, they had fewer glomeruli, and they developed stress-induced hypertension as adults. Their female siblings did not share this pathology and instead resembled progeny from WT dams. Surprisingly, glomerular counts in the neonatal period were not different between sexes or maternal genotypes. In turn, we suspect that differences in fetal renal DNA methylation may affect the long-term viability of glomeruli, rather than reducing nephrogenesis.

KW - Angiotensinogen

KW - Developmental programming

KW - DNA methylation

KW - Hypertension

KW - Nephrogenesis

UR - http://www.scopus.com/inward/record.url?scp=85080871936&partnerID=8YFLogxK

U2 - 10.1007/s43032-019-00121-5

DO - 10.1007/s43032-019-00121-5

M3 - Journal article

C2 - 32046425

AN - SCOPUS:85080871936

VL - 27

SP - 1110

EP - 1120

JO - Reproductive Sciences

JF - Reproductive Sciences

SN - 1933-7191

IS - 5

ER -