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

Stuart A Lanham,Richard O C Oreffo,Elizabeth Dupriest,Susan P Bagby,Cyrus Cooper,Philipp Kupfer

doi:10.14814/phy2.14081

Stuart A Lanham, Richard O C Oreffo + Show 4 more

Open Access

https://doi.org/10.14814/phy2.14081

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Abstract

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.

Highlights

Epidemiological data has suggested that the risk of developing a broad range of chronic diseases in adulthood, including cardiovascular disease and type 2 diabetes is influenced by genetic and life-style factors, and by environmental factors present in early life
Sows were housed at the Oregon Health & Science University (OHSU) Department of Comparative Medicine and experiments were approved by the OHSU Institutional Animal Care and Use Committee under protocol A439, under compliance with the Animal Welfare Act regulations and Public Health Service (PHS) Policy
The maternal low protein diet alone resulted in offspring with lower total Bone mineral content (BMC), lower hind leg and vertebrae BMC and raised total bone mineral density (BMD) at 6 weeks of age, and raised vertebral BMC at 11 weeks of age

Summary

Introduction

Epidemiological data has suggested that the risk of developing a broad range of chronic diseases in adulthood, including cardiovascular disease and type 2 diabetes is influenced by genetic and life-style factors, and by environmental factors present in early life. It has been hypothesized that the fetal response to maternalfetal nutritional stress leads to a phenotypic change which provides a fitness advantage in later life, altering its physiology to better match (“predict”) an adult environment which matches that experienced in utero. Such modifications have been termed predictive adaptive responses (Gluckman et al 2005). Through epidemiological evidence, reduced bone mass in the adult is associated with impaired growth during fetal life, infancy, and early childhood (Cooper et al 1997, 2002; Jones et al 2000; Tobias et al 2005) These observations indicate a link between maternal and fetal nutrition, peak bone mass, and fracture risk in later life. We present data from a larger mammalian model, the microswine, which show altered bone structure and density in the femur and vertebra in juvenile offspring from mothers fed a low protein diet during the last quarter of pregnancy and the early postnatal period, during which maximal bone development occurs

Ethical approval

Results

C Vertebra

D Ad Lib