Pancreas deficiency modifies bone development in the ovine fetus near term
Pancreas deficiency modifies bone development in the ovine fetus near term
Hormones have an important role in the regulation of fetal growth and development, especially in response to nutrient availability in utero. Using micro-CT and an electromagnetic three-point bend test, this study examined the effect of pancreas removal at 0.8 fraction of gestation on the developing bone structure and mechanical strength in fetal sheep. When fetuses were studied at 10 and 25 days after surgery, pancreatectomy caused hypoinsulinaemia, hyperglycaemia and growth retardation which was associated with low plasma concentrations of leptin and a marker of osteoclast activity and collagen degradation. In pancreatectomized fetuses compared to control fetuses, limb lengths were shorter, and trabecular (Tb) bone in the metatarsi showed greater bone volume fraction, Tb thickness, degree of anisotropy and porosity, and lower fractional bone surface area and Tb spacing. Mechanical strength testing showed that pancreas deficiency was associated with increased stiffness and a greater maximal weight load at fracture in a subset of fetuses studied near term. Overall, pancreas deficiency in utero slowed the growth of the fetal skeleton and adapted the developing bone to generate a more compact and connected structure. Maintenance of bone strength in growth-retarded limbs is especially important in a precocial species in preparation for skeletal loading and locomotion at birth.
Bone structure, Fetus, Glucose, Insulin, Leptin, Metatarsal, Micro-computed tomography, Pancreas, Skeleton
71-80
Oreffo, Richard
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Lanham, Stuart
28fdbbef-e3b6-4fdf-bd0f-4968eeb614d6
Fowden, Abigail L.
78847bb7-4d2d-4e79-93c8-a90e0131c1d6
Forhead, Alison J.
8ad02d28-a814-4b74-93ff-9c29a254019c
January 2022
Oreffo, Richard
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Lanham, Stuart
28fdbbef-e3b6-4fdf-bd0f-4968eeb614d6
Fowden, Abigail L.
78847bb7-4d2d-4e79-93c8-a90e0131c1d6
Forhead, Alison J.
8ad02d28-a814-4b74-93ff-9c29a254019c
Oreffo, Richard, Lanham, Stuart, Fowden, Abigail L. and Forhead, Alison J.
(2022)
Pancreas deficiency modifies bone development in the ovine fetus near term.
Journal of Endocrinology, 252 (1), .
(doi:10.1530/JOE-21-0189).
Abstract
Hormones have an important role in the regulation of fetal growth and development, especially in response to nutrient availability in utero. Using micro-CT and an electromagnetic three-point bend test, this study examined the effect of pancreas removal at 0.8 fraction of gestation on the developing bone structure and mechanical strength in fetal sheep. When fetuses were studied at 10 and 25 days after surgery, pancreatectomy caused hypoinsulinaemia, hyperglycaemia and growth retardation which was associated with low plasma concentrations of leptin and a marker of osteoclast activity and collagen degradation. In pancreatectomized fetuses compared to control fetuses, limb lengths were shorter, and trabecular (Tb) bone in the metatarsi showed greater bone volume fraction, Tb thickness, degree of anisotropy and porosity, and lower fractional bone surface area and Tb spacing. Mechanical strength testing showed that pancreas deficiency was associated with increased stiffness and a greater maximal weight load at fracture in a subset of fetuses studied near term. Overall, pancreas deficiency in utero slowed the growth of the fetal skeleton and adapted the developing bone to generate a more compact and connected structure. Maintenance of bone strength in growth-retarded limbs is especially important in a precocial species in preparation for skeletal loading and locomotion at birth.
Text
accepted JoE manuscript final
- Accepted Manuscript
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e-pub ahead of print date: 1 October 2021
Published date: January 2022
Additional Information:
Funding Information:
This work was supported by the BBSRC (grant number S18103) and Research into Ageing (grant number 253).
Funding Information:
This work was supported by the BBSRC (grant number S18103) and Research into Ageing (grant number 253). The authors are grateful to the members of the Universities of Cambridge, Southampton and Western Australia who provided technical assistance in this study. Plasma calcium concentration was measured by Dr Keith Burling, Department of Clinical Biochemistry, Addenbrooke?s Hospital, Cambridge.
Publisher Copyright:
© 2021 The authors Published by Bioscientifica Ltd.
Keywords:
Bone structure, Fetus, Glucose, Insulin, Leptin, Metatarsal, Micro-computed tomography, Pancreas, Skeleton
Identifiers
Local EPrints ID: 452610
URI: http://eprints.soton.ac.uk/id/eprint/452610
ISSN: 0022-0795
PURE UUID: 9c578c54-2a3e-4a83-a643-5ab97d0d3958
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Date deposited: 11 Dec 2021 11:29
Last modified: 17 Mar 2024 02:50
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Author:
Stuart Lanham
Author:
Abigail L. Fowden
Author:
Alison J. Forhead
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