Journal Article


Sex- and bone-specific responses in bone structure to exogenous leptin and leptin receptor antagonism in the ovine fetus

Abstract

Widespread expression of leptin and its receptor in developing cartilage and bone suggests that leptin may regulate bone growth and development in the fetus. Using micro-computed tomography, this study investigated the effects of exogenous leptin and leptin receptor antagonism on aspects of bone structure in the sheep fetus during late gestation. From 125-130 days of gestation (term ~145 days), chronically-catheterised singleton sheep fetuses were infused intravenously for five days with either saline (0.9% saline, n=13), recombinant ovine leptin at two doses (0.6 mg/kg/day LEP1, n=10 or 1.4 mg/kg/day LEP2, n=7) or recombinant super-active ovine leptin receptor antagonist (4.6 mg/kg/day SOLA, n=6). No significant differences in plasma insulin-like growth factor-I, osteocalcin, calcium, inorganic phosphate or alkaline phosphatase were observed between treatment groups. Total femur midshaft diameter and metatarsal lumen diameter were narrower in male fetuses treated with exogenous leptin. In a fixed length of femur midshaft, total and bone volumes were reduced by the higher dose of leptin; non-bone space volume was lower in both groups of leptin-treated fetuses. Leptin infusion caused increments in femur porosity and connectivity density, and vertebral trabecular thickness. Leptin receptor antagonism decreased trabecular spacing and increased trabecular number, degree of anisotrophy and connectivity density in the lumbar vertebrae. The increase in vertebral porosity observed following leptin receptor antagonism was greater in the male, compared to female, fetuses. Therefore, leptin may have a role in the growth and development of the fetal skeleton, dependent on the concentration of leptin, sex of the fetus and bone type examined.

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Authors

De Blasio, Miles J.
Lanham, Stuart A.
Blache, Dominique
Oreffo, Richard O. C.
Fowden, Abigail L.
Forhead, Alison J.

Oxford Brookes departments

Faculty of Health and Life Sciences\Department of Biological and Medical Sciences

Dates

Year of publication: 2018
Date of RADAR deposit: 2018-02-13


Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License


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