Maternal Periconceptional and Gestational Low Protein Diet Affects Mouse Offspring Growth, Cardiovascular and Adipose Phenotype at 1 Year of Age

School of Biological Sciences, University of Southampton, Southampton General Hospital, Southampton, United Kingdom.
PLoS ONE (Impact Factor: 3.23). 12/2011; 6(12):e28745. DOI: 10.1371/journal.pone.0028745
Source: PubMed


Human and animal studies have revealed a strong association between periconceptional environmental factors, such as poor maternal diet, and an increased propensity for cardiovascular and metabolic disease in adult offspring. Previously, we reported cardiovascular and physiological effects of maternal low protein diet (LPD) fed during discrete periods of periconceptional development on 6-month-old mouse offspring. Here, we extend the analysis in 1 year aging offspring, evaluating mechanisms regulating growth and adiposity. Isocaloric LPD (9% casein) or normal protein diet (18% casein; NPD) was fed to female MF-1 mice either exclusively during oocyte maturation (for 3.5 days prior to mating; Egg-LPD, Egg-NPD, respectively), throughout gestation (LPD, NPD) or exclusively during preimplantation development (for 3.5 days post mating; Emb-LPD). LPD and Emb-LPD female offspring were significantly lighter and heavier than NPD females respectively for up to 52 weeks. Egg-LPD, LPD and Emb-LPD offspring displayed significantly elevated systolic blood pressure at 52 weeks compared to respective controls (Egg-NPD, NPD). LPD females had significantly reduced inguinal and retroperitoneal fat pad: body weight ratios compared to NPD females. Expression of the insulin receptor (Insr) and insulin-like growth factor I receptor (Igf1r) in retroperitoneal fat was significantly elevated in Emb-LPD females (P<0.05), whilst Emb-LPD males displayed significantly decreased expression of the mitochondrial uncoupling protein 1 (Ucp1) gene compared to NPD offspring. LPD females displayed significantly increased expression of Ucp1 in interscapular brown adipose tissue when compared to NPD offspring. Our results demonstrate that aging offspring body weight, cardiovascular and adiposity homeostasis can be programmed by maternal periconceptional nutrition. These adverse outcomes further exemplify the criticality of dietary behaviour around the time of conception on long-term offspring health.


Available from: Felino R Cagampang
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    • " Vujkovic et al . 2010 , Twigt et al . 2012 ) . Long - term effects of these preconception diets for the offspring in humans are not known . However , interestingly the offspring from female mice fed a low protein diet ( LPD ) exclusively during oocyte maturation ( i . e . 3 . 5 days before mating ) displayed an increased systolic blood pressure ( Watkins et al . 2011 ) ."
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    • "Evidence from different experimental animal models showed that the exposure of embryos before implantation to adverse developmental conditions (i.e., undernutrition, overnutrition, and inflammation), both in vitro and in vivo, can not only hinder the embryonic quality and implantation success but also exert more subtle effects that are expressed later during intrauterine development or even during adulthood [26–28]. Programming of disease can occur as early as in oocytes and zygotes, by mechanisms including the aberrant methylation of genes involved in body homeostasis [29, 30], defective mitochondrial function [28, 31], and the inefficient generation of appropriately sized stem-cell lineages due to abnormal proliferation [32]. Our studies showed that exposure to maternal hypercholesterolemia exclusively before implantation was harmless to embryo growth, as LDLR KO females fed with the proatherogenic HC diet periconceptionally did not exhibit fetal growth restriction. "
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    • "In rats, maternal protein restriction during the periconceptional period induced a reduction in blastocyst cell number both within the inner cell mass and the trophectoderm [10], together with subsequent sex-dependent excess growth and hypertension in the offspring. In mice, maternal protein restriction during this period affected the function of the yolk sack, which developed enhanced endocytic capacity to increase nutrient retrieval [11], and induced sex-dependent effects on offspring growth, cardiovascular and adipose tissue phenotype [12]. Environmental conditions encountered by the embryo were thus shown to affect both embryonic and some extra-embryonic lineages, but the effects on the trophoblast have not been explored yet. "
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