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Periconception maternal low-protein diet adversely affects male mouse fetal bone growth and mineral density quality in late gestation

Published online by Cambridge University Press:  05 June 2020

Stuart A. Lanham ,
Stephanie J. Smith ,
Adam J. Watkins ,
Emma S. Lucas ,
Niamh MacCaoilte ,
Richard O.C. Oreffo ,
Tom P. Fleming  and
Judith J. Eckert Open the ORCID record for Judith J. Eckert [Opens in a new window]
Stuart A. Lanham
Affiliation:
Bone and Joint Research Group, Human Development and Health, Institute of Developmental Sciences, Faculty of Medicine, University of Southampton, SouthamptonSO16 6YD, UK
Stephanie J. Smith
Affiliation:
Biological Sciences, University of Southampton, SouthamptonSO16 6YD, UK
Adam J. Watkins
Affiliation:
School of Medicine, Division of Child Health, Obstetrics and Gynaecology, University of Nottingham, Queens Medical Centre, NottinghamNG7 2UH, UK
Emma S. Lucas
Affiliation:
Biological Sciences, University of Southampton, SouthamptonSO16 6YD, UK
Niamh MacCaoilte
Affiliation:
Biological Sciences, University of Southampton, SouthamptonSO16 6YD, UK
Richard O.C. Oreffo
Affiliation:
Bone and Joint Research Group, Human Development and Health, Institute of Developmental Sciences, Faculty of Medicine, University of Southampton, SouthamptonSO16 6YD, UK
Tom P. Fleming
Affiliation:
Biological Sciences, University of Southampton, SouthamptonSO16 6YD, UK
Judith J. Eckert*
Affiliation:
Human Development and Health, Institute of Developmental Sciences, Faculty of Medicine, University of Southampton, SouthamptonSO16 6YD, UK
*
Address for correspondence: Judith J. Eckert, MP887, Institute of Developmental Sciences, Southampton General Hospital, Tremona Road SO16 6YD, UK. Email: jje@soton.ac.uk
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Abstract

Adverse programming of adult non-communicable disease can be induced by poor maternal nutrition during pregnancy and the periconception period has been identified as a vulnerable period. In the current study, we used a mouse maternal low-protein diet fed either for the duration of pregnancy (LPD) or exclusively during the preimplantation period (Emb-LPD) with control nutrition provided thereafter and postnatally to investigate effects on fetal bone development and quality. This model has been shown previously to induce cardiometabolic and neurological disease phenotypes in offspring. Micro 3D computed tomography examination at fetal stages Embryonic day E14.5 and E17.4, reflecting early and late stages of bone formation, demonstrated LPD treatment caused increased bone formation of relative high mineral density quality in males, but not females, at E14.5, disproportionate to fetal growth, with bone quality maintained at E17.5. In contrast, Emb-LPD caused a late increase in male fetal bone growth, proportionate to fetal growth, at E17.5, affecting central and peripheral skeleton and of reduced mineral density quality relative to controls. These altered dynamics in bone growth coincide with increased placental efficiency indicating compensatory responses to dietary treatments. Overall, our data show fetal bone formation and mineral quality is dependent upon maternal nutritional protein content and is sex-specific. In particular, we find the duration and timing of poor maternal diet to be critical in the outcomes with periconceptional protein restriction leading to male offspring with increased bone growth but of poor mineral density, thereby susceptible to later disease risk.

Keywords

In uteromaternal nutritionmicro-computed tomographybonestructure
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 12 , Issue 3 , June 2021 , pp. 384 - 395
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2020

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