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Developmental programming of bone deficits in growth-restricted offspring
Tania Romano1, John D Wark2, Mary E Wlodek3
1Department of Human Biosciences, La Trobe University, Bundoora, Vic. 3086, Australia.
Insights
Low birth weight in rats due to uteroplacental insufficiency leads to significant bone deficits. These skeletal impairments, including reduced bone size and strength, show gender-specific differences and worsen with age.
Area of Science:
- Bone Biology
- Developmental Origins of Health and Disease (DOHaD)
Background:
- Emerging evidence suggests a link between low birth weight and compromised adult bone health.
- Uteroplacental insufficiency during gestation is a known cause of fetal growth restriction.
Purpose of the Study:
- To investigate the long-term effects of uteroplacental insufficiency on bone development and strength in rats.
- To characterize gender-specific skeletal changes from weaning through adulthood.
Main Methods:
- Uteroplacental insufficiency was induced in pregnant rats via bilateral uterine vessel ligation.
- Offspring bone characteristics (size, mineral content, density, strength) were assessed using quantitative computed tomography (pQCT) at multiple time points.
- Bone strength was evaluated using the stress-strain index (SSI).
Main Results:
- Restricted offspring exhibited reduced femur length and bone mineral content compared to controls.
- Trabecular bone content was lower in restricted rats, while cortical bone content and density were reduced, particularly in females.
- Stress-strain index (SSI) indicated significantly lower bone strength in restricted males and females across various ages, with some deficits worsening over time.
Conclusions:
- Uteroplacental insufficiency during gestation results in persistent skeletal deficits in offspring.
- Observed bone impairments display distinct gender-specific patterns and can be exacerbated by aging.
- These findings highlight the critical impact of early-life nutrition and development on long-term bone health.
Abstract:
Recent evidence links low birthweight and poor adult bone health. We characterised bone size, mineral content, density and strength (stress strain index of bone bending strength (SSI)) in rats from weaning to 12 months. Bilateral uterine vessel ligation (Restricted) or sham surgery (Control) was performed on gestational Day 18 in rats inducing uteroplacental insufficiency. Postmortem of male and female offspring was performed at postnatal Day 35 and at 2, 4, 6 and 12 months. Femur mineral content, density and strength were measured using quantitative computed tomography (pQCT). Restricted pups were born 10%-15% lighter and remained smaller with shorter femurs than Controls (P<0.05). Male and female Restricted rats had lower trabecular bone content compared with Controls (P<0.05), without trabecular density changes. Cortical content was reduced in Restricted males (Day 35 and 6 and 12 months) and at all ages in Restricted females (P<0.05). Cortical density was lower at Day 35 in Restricted males (P<0.05). SSI was lower at Day 35 and at 6 and 12 months in Restricted males, and at all ages in Restricted females (P<0.05). Skeletal deficits were detected in Restricted offspring with gender-specific differences during juvenile and adolescent periods. Bone deficits observed at 6 months in males were greater than at 12 months, indicating that aging can exacerbate programmed bone phenotypes.
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