Animal models of maternal nutrition and altered offspring bone structure – Bone development across the lifecourse

Lanham, Stuart; Bertram, C.; Cooper, Cyrus; Oreffo, R.O.C.

doi:10.22203/ecm.v022a24

Cited by 19 publications

(22 citation statements)

References 88 publications

(51 reference statements)

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“…These data suggest the increased levels of Gas6 in the aorta from female HF/HF offspring may, ultimately, result in greater susceptibility in these animals to vascular disease. As with previous studies (36), there is evidence that the maternal diet can alter the offspring skeletal response to the postnatal diet. The maternal diet has a larger influence than the offspring diet on parameters such as femur bone volume and length, and vertebral body length, whereas the offspring diet produced the most significant effects and influence on mass and femora midshaft wall thickness parameters in males.…”

Section: Discussionsupporting

confidence: 71%

Maternal High-Fat Diet and Offspring Expression Levels of Vitamin K–Dependent Proteins

2014

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Studies suggest that bone growth and development and susceptibility to vascular disease in later life are influenced by maternal nutrition during intrauterine and early postnatal life. There is evidence for a role of vitamin K-dependent proteins (VKDPs) including osteocalcin, matrix Gla protein, periostin, and growth-arrest specific- protein 6, in both bone and vascular development. We have examined whether there are alterations in these VKDPs in bone and vascular tissue from offspring of mothers subjected to a nutritional challenge: a high-fat diet during pregnancy and postnatally, using 6-week-old mouse offspring. Bone site-specific and sex-specific differences across femoral and vertebral bone in male and female offspring were observed. Overall a high-fat maternal diet and offspring diet exacerbated the bone changes observed. Sex-specific differences and tissue-specific differences were observed in VKDP levels in aorta tissue from high-fat diet-fed female offspring from high-fat diet-fed mothers displaying increased levels of Gas6 and Ggcx compared with those of female controls. In contrast, differences were seen in VKDP levels in femoral bone of female offspring with lower expression levels of Mgp in offspring of mothers fed a high-fat diet compared with those of controls. We observed a significant correlation in Mgp expression levels within the femur to measures of bone structure of the femur and vertebra, particularly in the male offspring cohort. In summary, the current study has highlighted the importance of maternal nutrition on offspring bone development and the correlation of VKDPs to bone structure.

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Section: Discussionsupporting

confidence: 71%

Maternal High-Fat Diet and Offspring Expression Levels of Vitamin K–Dependent Proteins

2014

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“…This is in agreement with previous studies which have shown male rat offspring are less affected than females by maternal diet (Lanham et al. ).…”

Section: Discussionsupporting

confidence: 94%

“…Interestingly, the differences seen in the vertebra between the control and low protein offspring groups (trabecular spacing, trabecular number per mm, and SMI) when ad lib and calorie-restricted groups were combined, showed larger differences in females than males. This is in agreement with previous studies which have shown male rat offspring are less affected than females by maternal diet (Lanham et al 2011). The purpose of the postweaning calorie restriction was to prevent the subsequent catch-up growth seen when low protein diet restriction was removed.…”

Section: Discussionsupporting

confidence: 92%

Altered vertebral and femoral bone structure in juvenile offspring of microswine subject to maternal low protein nutritional challenge

et al. 2019

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Epidemiological studies suggest skeletal growth is programmed during intrauterine and early postnatal life. We hypothesize that bone development may be altered by maternal diet and have investigated this using a microswine model of maternal protein restriction (MPR). Mothers were fed a control diet (14% protein) or isocaloric low (1%) protein diet during late pregnancy and for 2 weeks postnatally. Offspring were weaned at 4 weeks of age to ad lib or calorie‐restricted food intake groups. Femur and vertebra were analysed by micro computed tomography in offspring 3–5 months of age. Caloric restriction from 4 weeks of age, designed to prevent catch‐up growth, showed no significant effects on bone structure in the offspring from either maternal dietary group. A maternal low protein diet altered trabecular number in the proximal femur and vertebra in juvenile offspring. Cortical bone was unaffected. These results further support the need to understand the key role of the nutritional environment in early development on programming of skeletal development and consequences in later life.

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“…Nutrition and mechanical strain each can influence fetal bone morphology. Poor maternal nutrition can lead to an under-mineralized and misshapen infant skeleton (Lanham et al, 2011). Biomechanical influences on bone growth, development, and mineralization depend on the muscular activity of the fetus, as well as the activity of the mother (Carter et al, 1987;Rodriguez et al, 1988;Carter et al, 1991).…”

Section: Environmental Influencesmentioning

confidence: 99%

Skeletal growth and the changing genetic landscape during childhood and adulthood

Duren

Šešelj

Froehle

et al. 2012

American J Phys Anthropol

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Growth, development, and decline of the human skeleton are of central importance to physical anthropology. All processes of skeletal growth (longitudinal growth as well as gains and losses of bone mass) are subject to environmental and genetic influences. These influences, and their relative contributions to the phenotype, can be asserted at any stage of life. We present here the gross phenotypic and genetic landscapes of four skeletal traits, and show how they vary across the life span. Phenotypic sex differences are found in bone diameter and cortical index (a ratio of cortical thickness over bone diameter) at a very early age and continue throughout most of life. Sexual dimorphism in summed cortical thickness and bone length, however, is not evident until shortly after the pubertal growth spurt. Genetic contributions (heritability) to these skeletal phenotypes are generally moderate to high. Bone length and bone diameter (which both scale with body size) tend to have the highest heritability, with heritability of bone length fairly stable across ages (with a notable dip in early childhood) and that of bone diameter peaking in early childhood. The bone traits summed cortical thickness and cortical index, that may better reflect bone mass, a more plastic phenomenon, have slightly lower genetic influences, on average. Results from our phenotypic and genetic landscapes serve three key purposes: demonstration of the integrated nature of the genetic and environmental underpinnings of skeletal form; identification of periods of bone’s relative sensitivity to genetic and environmental influences; and stimulation of hypotheses predicting the effects of exposure to environmental variables on the skeleton, given variation in the underlying genetic architecture.

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Animal models of maternal nutrition and altered offspring bone structure – Bone development across the lifecourse

Cited by 19 publications

References 88 publications

Maternal High-Fat Diet and Offspring Expression Levels of Vitamin K–Dependent Proteins

Maternal High-Fat Diet and Offspring Expression Levels of Vitamin K–Dependent Proteins

Altered vertebral and femoral bone structure in juvenile offspring of microswine subject to maternal low protein nutritional challenge

Skeletal growth and the changing genetic landscape during childhood and adulthood

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