Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-26T08:58:41.819Z Has data issue: false hasContentIssue false
  • English
  • Français

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
Get access Rights & Permissions [Opens in a new window]

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
Check for updates
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Barker, DJ, Thornburg, KL. The obstetric origins of health for a lifetime. Clin Obstet Gynecol. 2013; 56, 511–519.CrossRefGoogle ScholarPubMed
Langley-Evans, SC. Fetal programming of CVD and renal disease: animal models and mechanistic considerations. Proc Nutr Soc. 2013; 72, 317–325.CrossRefGoogle ScholarPubMed
Fleming, TP, Watkins, AJ, Velazquez, MA, et al. Origins of lifetime health around the time of conception: causes and consequences. Lancet. 2018; 391, 1842–1852.CrossRefGoogle ScholarPubMed
Jones, G, Riley, MD, Dwyer, T. Maternal diet during pregnancy is associated with bone mineral density in children: a longitudinal study. Eur J Clin Nutr. 2000; 54, 749–756.CrossRefGoogle ScholarPubMed
Tobias, JH, Steer, CD, Emmett, PM, Tonkin, RJ, Cooper, C, Ness, AR. Bone mass in childhood is related to maternal diet in pregnancy. Osteoporos Int. 2005; 16, 1731–1741.CrossRefGoogle ScholarPubMed
Yin, J, Dwyer, T, Riley, M, Cochrane, J, Jones, G. The association between maternal diet during pregnancy and bone mass of the children at age 16. Eur J Clin Nutr. 2010; 64, 131–137.CrossRefGoogle ScholarPubMed
Lanham, SA, Bertram, C, Cooper, C, Oreffo, RO. Animal models of maternal nutrition and altered offspring bone structure – bone development across the lifecourse. Eur Cell Mater. 2011; 22, 321–332; discussion 332.CrossRefGoogle ScholarPubMed
Cooper, C, Javaid, MK, Taylor, P, Walker-Bone, K, Dennison, E, Arden, N. The fetal origins of osteoporotic fracture. Calcif Tissue Int. 2002; 70, 391–394.CrossRefGoogle ScholarPubMed
Petry, CJ, Dorling, MW, Pawlak, DB, Ozanne, SE, Hales, CN. Diabetes in old male offspring of rat dams fed a reduced protein diet. Int J Exp Diabetes Res. 2001; 2, 139–143.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Welham, SJ, Jackson, AA. Fetal exposure to a maternal low protein diet impairs nephrogenesis and promotes hypertension in the rat. Life Sci. 1999; 64, 965–974.CrossRefGoogle ScholarPubMed
Lanham, SA, Roberts, C, Cooper, C, Oreffo, RO. Intrauterine programming of bone. Part 1: alteration of the osteogenic environment. Osteoporos Int. 2008; 19, 147–156.CrossRefGoogle ScholarPubMed
Lanham, SA, Roberts, C, Perry, MJ, C. Cooper, C, Oreffo, RO. Intrauterine programming of bone. Part 2: alteration of skeletal structure. Osteoporos Int. 2008; 19, 157–167.CrossRefGoogle ScholarPubMed
Kwong, WY, Wild, AE, Roberts, P, Willis, AC, Fleming, TP. Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development. 2000; 127, 4195–4202.CrossRefGoogle ScholarPubMed
Watkins, AJ, Ursell, JE, Panton, R, et al. Adaptive responses by mouse early embryos to maternal diet protect fetal growth but predispose to adult onset disease. Biol Reprod. 2008; 78, 299–306.CrossRefGoogle ScholarPubMed
Gould, JM, Smith, PJ, Airey, CJ, et al. Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory. Proc Natl Acad Sci U S A. 2018; 115, E7398–E7407.CrossRefGoogle ScholarPubMed
Watkins, AJ, Sirovica, S, Stokes, B, Isaacs, M, Addison, O, Martin, RA. Paternal low protein diet programs preimplantation embryo gene expression, fetal growth and skeletal development in mice. Biochim Biophys Acta. 2017; 1863, 1371–1381.CrossRefGoogle ScholarPubMed
Watkins, AJ, Lucas, ES, Wilkins, A, Cagampang, FR, Fleming, TP. Maternal periconceptional and gestational low protein diet affects mouse offspring growth, cardiovascular and adipose phenotype at 1 year of age. PLoS One. 2011; 6, e28745.CrossRefGoogle ScholarPubMed
Patton, JT, Kaufman, MH. The timing of ossification of the limb bones, and growth rates of various long bones of the fore and hind limbs of the prenatal and early postnatal laboratory mouse. J Anat. 1995; 186, 175–185.Google ScholarPubMed
Rigueur, D, Lyons, KM. Whole-mount skeletal staining. Methods Mol Biol. 2014; 1130, 113–121.CrossRefGoogle ScholarPubMed
Huang, LF, Fukai, N, Selby, PB, Olsen, BR, Mundlos, S. Mouse clavicular development: analysis of wild-type and cleidocranial dysplasia mutant mice. Dev Dyn. 1997; 210, 33–40.3.0.CO;2-2>CrossRefGoogle ScholarPubMed
Thornburg, KL, Kolahi, K, Pierce, M, Valent, A, Drake, R, Louey, S. Biological features of placental programming. Placenta. 2016; 48 Suppl 1, S47–S53.CrossRefGoogle Scholar
Coan, PM, Vaughan, OR, McCarthy, J, et al. Dietary composition programmes placental phenotype in mice. J Physiol. 2011; 589, 3659–3670.CrossRefGoogle ScholarPubMed
Eckert, JJ, Porter, R, Watkins, AJ, et al. Metabolic induction and early responses of mouse blastocyst developmental programming following maternal low protein diet affecting life-long health. PLoS One. 2012; 7, e52791.CrossRefGoogle ScholarPubMed
Sun, C, Velazquez, MA, Marfy-Smith, S, et al. Mouse early extra-embryonic lineages activate compensatory endocytosis in response to poor maternal nutrition. Development. 2014; 141, 1140–1150.CrossRefGoogle ScholarPubMed
Watkins, AJ, Lucas, ES, Marfy-Smith, S, Bates, N, Kimber, SJ, Fleming, TP. Maternal nutrition modifies trophoblast giant cell phenotype and fetal growth in mice. Reproduction. 2015; 149, 563–575.CrossRefGoogle ScholarPubMed
Sun, C, Denisenko, O, Sheth, B, et al. Epigenetic regulation of histone modifications and Gata6 gene expression induced by maternal diet in mouse embryoid bodies in a model of developmental programming. BMC Dev Biol. 2015; 15, 3.CrossRefGoogle Scholar
Denisenko, O, Lucas, ES, Sun, C, et al. Regulation of ribosomal RNA expression across the lifespan is fine-tuned by maternal diet before implantation. Biochim Biophys Acta. 2016; 1859, 906–913.CrossRefGoogle ScholarPubMed