Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring

Adam J. Watkins, Adrian Wilkins, Colm Cunningham, V. Hugh Perry, Meei J. Seet, Clive Osmond, Judith J. Eckert, Christopher Torrens, Felino R.A. Cagampang, Jane Cleal, William P. Gray, Mark A. Hanson, Tom P. Fleming

Research output: Contribution to journalArticle

Abstract

Early embryonic development is known to be susceptible to maternal undernutrition, leading to a disease-related postnatal phenotype. To determine whether this sensitivity extended into oocyte development, we examined the effect of maternal normal protein diet (18% casein; NPD) or isocaloric low protein diet (9% casein; LPD) restricted to one ovulatory cycle (3.5 days) prior to natural mating in female MF-1 mice. After mating, all females received NPD for the remainder of gestation and all offspring were litter size adjusted and fed standard chow. No difference in gestation length, litter size, sex ratio or postnatal growth was observed between treatments. Maternal LPD did, however, induce abnormal anxiety-related behaviour in open field activities in male and female offspring (P <0.05). Maternal LPD offspring also exhibited elevated systolic blood pressure (SBP) in males at 9 and 15 weeks and in both sexes at 21 weeks (P <0.05). Male LPD offspring hypertension was accompanied by attenuated arterial responsiveness in vitro to vasodilators acetylcholine and isoprenaline (P <0.05). LPD female offspring adult kidneys were also smaller, but had increased nephron numbers (P <0.05). Moreover, the relationship between SBP and kidney or heart size or nephron number was altered by diet treatment (P <0.05). These data demonstrate the sensitivity of mouse maturing oocytes in vivo to maternal protein undernutrition and identify both behavioural and cardiovascular postnatal outcomes, indicative of adult disease. These outcomes probably derive from a direct effect of protein restriction, although indirect stress mechanisms may also be contributory. Similar and distinct postnatal outcomes were observed here compared with maternal LPD treatment during post-fertilization preimplantation development which may reflect the relative contribution of the paternal genome.
Original languageEnglish
Pages (from-to)2231-2244
Number of pages14
JournalJournal of Physiology
Volume586
Issue number8
DOIs
Publication statusPublished - 15 Apr 2008

Fingerprint

Cardiovascular Abnormalities
Protein-Restricted Diet
Oocytes
Mothers
Blood Pressure
Litter Size
Nephrons
Caseins
Malnutrition
Diet
Kidney
Pregnancy
Proteins
Sex Ratio
Vasodilator Agents
Isoproterenol
Fertilization
Acetylcholine
Embryonic Development
Therapeutics

Bibliographical note

This is the accepted version of the following article: Watkins, A. J., Wilkins, A., Cunningham, C., Perry, V. H., Seet, M. J., Osmond, C., Eckert, J. J., Torrens, C., Cagampang, F. R. A., Cleal, J., Gray, W. P., Hanson, M. A., & Fleming, T. P. (2008). Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring. Journal of physiology, 586(8), 2231-2244., which has been published in final form at http://dx.doi.org/10.1113/jphysiol.2007.149229

Cite this

Watkins, A. J., Wilkins, A., Cunningham, C., Perry, V. H., Seet, M. J., Osmond, C., ... Fleming, T. P. (2008). Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring. Journal of Physiology, 586(8), 2231-2244. https://doi.org/10.1113/jphysiol.2007.149229
Watkins, Adam J. ; Wilkins, Adrian ; Cunningham, Colm ; Perry, V. Hugh ; Seet, Meei J. ; Osmond, Clive ; Eckert, Judith J. ; Torrens, Christopher ; Cagampang, Felino R.A. ; Cleal, Jane ; Gray, William P. ; Hanson, Mark A. ; Fleming, Tom P. / Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring. In: Journal of Physiology. 2008 ; Vol. 586, No. 8. pp. 2231-2244.
@article{c052f2b7691846daaf3046bb8c58da15,
title = "Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring",
abstract = "Early embryonic development is known to be susceptible to maternal undernutrition, leading to a disease-related postnatal phenotype. To determine whether this sensitivity extended into oocyte development, we examined the effect of maternal normal protein diet (18{\%} casein; NPD) or isocaloric low protein diet (9{\%} casein; LPD) restricted to one ovulatory cycle (3.5 days) prior to natural mating in female MF-1 mice. After mating, all females received NPD for the remainder of gestation and all offspring were litter size adjusted and fed standard chow. No difference in gestation length, litter size, sex ratio or postnatal growth was observed between treatments. Maternal LPD did, however, induce abnormal anxiety-related behaviour in open field activities in male and female offspring (P <0.05). Maternal LPD offspring also exhibited elevated systolic blood pressure (SBP) in males at 9 and 15 weeks and in both sexes at 21 weeks (P <0.05). Male LPD offspring hypertension was accompanied by attenuated arterial responsiveness in vitro to vasodilators acetylcholine and isoprenaline (P <0.05). LPD female offspring adult kidneys were also smaller, but had increased nephron numbers (P <0.05). Moreover, the relationship between SBP and kidney or heart size or nephron number was altered by diet treatment (P <0.05). These data demonstrate the sensitivity of mouse maturing oocytes in vivo to maternal protein undernutrition and identify both behavioural and cardiovascular postnatal outcomes, indicative of adult disease. These outcomes probably derive from a direct effect of protein restriction, although indirect stress mechanisms may also be contributory. Similar and distinct postnatal outcomes were observed here compared with maternal LPD treatment during post-fertilization preimplantation development which may reflect the relative contribution of the paternal genome.",
author = "Watkins, {Adam J.} and Adrian Wilkins and Colm Cunningham and Perry, {V. Hugh} and Seet, {Meei J.} and Clive Osmond and Eckert, {Judith J.} and Christopher Torrens and Cagampang, {Felino R.A.} and Jane Cleal and Gray, {William P.} and Hanson, {Mark A.} and Fleming, {Tom P.}",
note = "This is the accepted version of the following article: Watkins, A. J., Wilkins, A., Cunningham, C., Perry, V. H., Seet, M. J., Osmond, C., Eckert, J. J., Torrens, C., Cagampang, F. R. A., Cleal, J., Gray, W. P., Hanson, M. A., & Fleming, T. P. (2008). Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring. Journal of physiology, 586(8), 2231-2244., which has been published in final form at http://dx.doi.org/10.1113/jphysiol.2007.149229",
year = "2008",
month = "4",
day = "15",
doi = "10.1113/jphysiol.2007.149229",
language = "English",
volume = "586",
pages = "2231--2244",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",
number = "8",

}

Watkins, AJ, Wilkins, A, Cunningham, C, Perry, VH, Seet, MJ, Osmond, C, Eckert, JJ, Torrens, C, Cagampang, FRA, Cleal, J, Gray, WP, Hanson, MA & Fleming, TP 2008, 'Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring', Journal of Physiology, vol. 586, no. 8, pp. 2231-2244. https://doi.org/10.1113/jphysiol.2007.149229

Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring. / Watkins, Adam J.; Wilkins, Adrian; Cunningham, Colm; Perry, V. Hugh; Seet, Meei J.; Osmond, Clive; Eckert, Judith J.; Torrens, Christopher; Cagampang, Felino R.A.; Cleal, Jane; Gray, William P.; Hanson, Mark A.; Fleming, Tom P.

In: Journal of Physiology, Vol. 586, No. 8, 15.04.2008, p. 2231-2244.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring

AU - Watkins, Adam J.

AU - Wilkins, Adrian

AU - Cunningham, Colm

AU - Perry, V. Hugh

AU - Seet, Meei J.

AU - Osmond, Clive

AU - Eckert, Judith J.

AU - Torrens, Christopher

AU - Cagampang, Felino R.A.

AU - Cleal, Jane

AU - Gray, William P.

AU - Hanson, Mark A.

AU - Fleming, Tom P.

N1 - This is the accepted version of the following article: Watkins, A. J., Wilkins, A., Cunningham, C., Perry, V. H., Seet, M. J., Osmond, C., Eckert, J. J., Torrens, C., Cagampang, F. R. A., Cleal, J., Gray, W. P., Hanson, M. A., & Fleming, T. P. (2008). Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring. Journal of physiology, 586(8), 2231-2244., which has been published in final form at http://dx.doi.org/10.1113/jphysiol.2007.149229

PY - 2008/4/15

Y1 - 2008/4/15

N2 - Early embryonic development is known to be susceptible to maternal undernutrition, leading to a disease-related postnatal phenotype. To determine whether this sensitivity extended into oocyte development, we examined the effect of maternal normal protein diet (18% casein; NPD) or isocaloric low protein diet (9% casein; LPD) restricted to one ovulatory cycle (3.5 days) prior to natural mating in female MF-1 mice. After mating, all females received NPD for the remainder of gestation and all offspring were litter size adjusted and fed standard chow. No difference in gestation length, litter size, sex ratio or postnatal growth was observed between treatments. Maternal LPD did, however, induce abnormal anxiety-related behaviour in open field activities in male and female offspring (P <0.05). Maternal LPD offspring also exhibited elevated systolic blood pressure (SBP) in males at 9 and 15 weeks and in both sexes at 21 weeks (P <0.05). Male LPD offspring hypertension was accompanied by attenuated arterial responsiveness in vitro to vasodilators acetylcholine and isoprenaline (P <0.05). LPD female offspring adult kidneys were also smaller, but had increased nephron numbers (P <0.05). Moreover, the relationship between SBP and kidney or heart size or nephron number was altered by diet treatment (P <0.05). These data demonstrate the sensitivity of mouse maturing oocytes in vivo to maternal protein undernutrition and identify both behavioural and cardiovascular postnatal outcomes, indicative of adult disease. These outcomes probably derive from a direct effect of protein restriction, although indirect stress mechanisms may also be contributory. Similar and distinct postnatal outcomes were observed here compared with maternal LPD treatment during post-fertilization preimplantation development which may reflect the relative contribution of the paternal genome.

AB - Early embryonic development is known to be susceptible to maternal undernutrition, leading to a disease-related postnatal phenotype. To determine whether this sensitivity extended into oocyte development, we examined the effect of maternal normal protein diet (18% casein; NPD) or isocaloric low protein diet (9% casein; LPD) restricted to one ovulatory cycle (3.5 days) prior to natural mating in female MF-1 mice. After mating, all females received NPD for the remainder of gestation and all offspring were litter size adjusted and fed standard chow. No difference in gestation length, litter size, sex ratio or postnatal growth was observed between treatments. Maternal LPD did, however, induce abnormal anxiety-related behaviour in open field activities in male and female offspring (P <0.05). Maternal LPD offspring also exhibited elevated systolic blood pressure (SBP) in males at 9 and 15 weeks and in both sexes at 21 weeks (P <0.05). Male LPD offspring hypertension was accompanied by attenuated arterial responsiveness in vitro to vasodilators acetylcholine and isoprenaline (P <0.05). LPD female offspring adult kidneys were also smaller, but had increased nephron numbers (P <0.05). Moreover, the relationship between SBP and kidney or heart size or nephron number was altered by diet treatment (P <0.05). These data demonstrate the sensitivity of mouse maturing oocytes in vivo to maternal protein undernutrition and identify both behavioural and cardiovascular postnatal outcomes, indicative of adult disease. These outcomes probably derive from a direct effect of protein restriction, although indirect stress mechanisms may also be contributory. Similar and distinct postnatal outcomes were observed here compared with maternal LPD treatment during post-fertilization preimplantation development which may reflect the relative contribution of the paternal genome.

UR - http://www.scopus.com/inward/record.url?scp=42149090406&partnerID=8YFLogxK

U2 - 10.1113/jphysiol.2007.149229

DO - 10.1113/jphysiol.2007.149229

M3 - Article

AN - SCOPUS:42149090406

VL - 586

SP - 2231

EP - 2244

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 8

ER -