Offspring Bone Development Research Articles

Effect of high-fructose consumption in pregnancy on the bone growth of offspring rats.

Growing evidence suggests that bone health is programmed in early life. Maternal diet may influence the skeletal development of offspring. We aimed to determine the possible effects of high-fructose intake during pregnancy on different aspects of long bone morphology in the offspring of rats and to initially explore the possible mechanisms. Pregnant Sprague-Dawley rats were randomly divided into four groups and intragastrically administered the same dose of distilled water (CON, n = 12), 20 g/kg/day glucose (GLU, n = 12), 10 g/kg/day fructose (LFRU, n = 12), or 20 g/kg/day fructose (HFRU, n = 12) for 21 days during gestation. Computed tomography was used to analyze the cortical and cancellous bones of the distal femur of the offspring rats, and circulating bone metabolic biomarkers were measured using enzyme immunoassay. The results showed that high-fructose intake during pregnancy could decrease body weight, impair glucose metabolism, and increase serum leptin and uric acid in offspring. The offspring in the HFRU group had higher levels of the N-terminal propeptide of type I procollagen (PINP) and the C-telopeptide of type I collagen (CTX). The bone mean density (BMD), the total cross-sectional area inside the periosteal envelope (Tt.Ar), cortical bone area (Ct.Ar), medullary (or marrow) area (Ma.Ar), and trabecular mean density of the offspring in the HFRU group were lower than those in the CON group. Tartrate-resistant acid phosphatase (Trap) staining showed that high-fructose intake during pregnancy could increase the number of osteoclasts and increase the absorption area. Our results suggested that excessive fructose intake during pregnancy could inhibit skeletal development in offspring. Thus, attention to fructose intake during pregnancy is important for bone development in offspring.

Bone development in offspring of pregnant rats treated with carbamazepine: Evaluation by three different methods.

This study was carried out to determine the effect of intrauterine carbamazepine (CBZ) exposure on fetal bone development during pregnancy. In the study, 24 female Wistar pregnant rats were used. Rats were 20 weeks old. They had an average body weight of 150-200 g. Pregnant rats were randomly selected and divided (n= 6) into a control group, low-dose CBZ (10 mg/kg/day) group, medium-dose CBZ (25 mg/kg/day) group, and high-dose CBZ (50 mg/kg/day) group. The ossification length (mm) and ossification area (mm2 ) of the long bones of the fetuses in the experimental and control groups were calculated. The densities of alkaline phosphatase (AP) and tartrate-resistant acid phosphatase (TRAP) were analyzed. The ossification regions of the femurs of the fetuses were examined under a light microscope. Microstructural images of the femurs were evaluated with scanning electron microscope photographs. The densities of minerals involved in the ossification process were analyzed. According to the results of the study, all three doses of CBZ caused loss of ossification areas, and it was observed that this bone loss also increased statistically significantly depending on the dose increase (p< .05). Calcium concentration decreased in the CBZ groups. When the electron microscope images were examined, it was determined that the cartilage matrix of the CBZ groups was thinned. In the histological evaluation of the groups, narrowing of the primary bone collar and smaller bone spicules in the ossification region compared to the control group were noted due to the increase in dose in the CBZ groups. In immunohistochemical staining, it was observed that the TRAP and AP expression values of the femurs were the lowest in the CBZ groups. These decreases were also statistically significant when compared with the control group. It was revealed with both microscopic and macroscopic findings that exposure to intrauterine CBZ negatively affected ossification and bone growth.

Positive programming of the GC-IGF1 axis mediates adult osteoporosis susceptibility in male offspring rats induced by prenatal dexamethasone exposure

Prenatal dexamethasone exposure (PDE) can lead to offspring long bone dysplasia and continue to postnatal, and this is an important cause of fetal-derived osteoporosis. Studies have confirmed that intrauterine endogenous GC overexposure mediates multiple organ dysplasia and adult-related disease susceptibility in offspring through the glucocorticoid-insulin-like growth factor1 (GC-IGF1) axis. However, it remains unknown if exogenous dexamethasone can regulate bone development in offspring through the GC-IGF1 axis. We determined that the PDE fetal rats exhibited poor osteogenic differentiation, decreased bone mass that continued to adolescence, and increased susceptibility to osteoporosis in adulthood. Concurrently, PDE decreased the serum corticosterone concentration and IGF1 expression in offspring before and after birth, while the increased serum corticosterone concentration induced by chronic stress reversed the inhibition of IGF1 expression induced by PDE. Furthermore, PDE decreased the expression of GRα and miR-130a-5p, increased HDAC4, and decreased H3K27 acetylation in the IGF1 promoter region in bone tissue, and the above changes were negatively compensated after chronic stress. In vitro, a low concentration of corticosterone inhibited the expression of GRα and miR130a-5p, upregulated the expression of HDAC4, inhibited the promoter region H3K27 acetylation, and expression of IGF1 in bone marrow mesenchymal stem cell (BMSCs) osteoblast differentiated cells and inhibited osteogenic differentiation of BMSCs. GRα overexpression, miR-130a-5p mimic treatment, or HDAC4 siRNA exposure reversed the downstream molecular alterations caused by low corticosterone concentrations. In conclusion, PDE-induced intrauterine hypoglucocorticoid exposure could positively program IGF1 expression in bone tissue through the GRα/miR-130a-5p/HDAC4 pathways, thus mediating osteogenic dysdifferentiation and adult osteoporosis susceptibility in male offspring rats.

Maternal high-cholesterol diet negatively programs offspring bone development and downregulates hedgehog signaling in osteoblasts

Cholesterol is one of the essential intrauterine factors required for fetal growth and development. Maternal high cholesterol levels are known to be detrimental for offspring health. However, its long-term effect on offspring skeletal development remains to be elucidated. We performed our studies in two strains of mice (C57BL6/J and Swiss Albino) and human subjects (65 mother–female newborn dyads) to understand the regulation of offspring skeletal growth by maternal high cholesterol. We found that mice offspring from high-cholesterol-fed dams had low birth weight, smaller body length, and delayed skeletal ossification at the E18.5 embryonic stage. Moreover, we observed that the offspring did not recover from the reduced skeletal mass and exhibited a low bone mass phenotype throughout their life. We attributed this effect to reduced osteoblast cell activity with a concomitant increase in the osteoclast cell population. Our investigation of the molecular mechanism revealed that offspring from high-cholesterol-fed dams had a decrease in the expression of ligands and proteins involved in hedgehog signaling. Further, our cross-sectional study of human subjects showed a significant inverse correlation between maternal blood cholesterol levels and cord blood bone formation markers. Moreover, the bone formation markers were significantly lower in the female newborns of hypercholesterolemic mothers compared with mothers with normal cholesterolemic levels. Together, our results suggest that maternal high cholesterol levels deleteriously program offspring bone mass and bone quality and downregulate the hedgehog signaling pathway in their osteoblasts.

Pregnancy and Lactation in Sprague-Dawley Rats Result in Permanent Reductions of Tibia Trabecular Bone Mineral Density and Structure but Consumption of Red Rooibos Herbal Tea Supports the Partial Recovery.

During pregnancy and lactation, maternal bone mineral density (BMD) is reduced as calcium is mobilized to support offspring bone development. In humans, BMD returns to pre-pregnancy levels shortly after delivery, shifting from a high rate of bone resorption during pregnancy and lactation, into a rapid phase of bone formation post-lactation. This rapid change in bone turnover may provide an opportunity to stimulate a greater gain in BMD and stronger trabecular and cortical structure than present pre-pregnancy. Providing polyphenols present in red rooibos herbal tea may promote such an effect. In vitro, red rooibos polyphenols stimulate osteoblast activity, reduce osteoclastic resorption, and increase mineral production. The study objective was to determine if consuming red rooibos from pre-pregnancy through to 4 months post-lactation resulted in a higher BMD and improved trabecular and cortical bone structure in a commonly used rat model. Female Sprague-Dawley rats (n = 42) were randomized to one of the following groups: PREG TEA (pregnant, received supplemental level of red rooibos in water: ~2.6 g /kg body weight/day in water), PREG WATER (pregnant, received water), or NONPREG CON (age-matched, non-pregnant control, received water) from 2 weeks pre-pregnancy (age 8 weeks) through to 4 months post-lactation. Rats were fed AIN-93G (pre-pregnancy through to the end of lactation) and AIN-93M (post-lactation onwards). BMD and trabecular structure (bone volume fraction, trabecular number, trabecular separation) were improved (p < 0.05) by 1- or 2-months post-lactation when comparing PREG TEA to PREG CON, though neither group recovered to the level of NONPREG CON. Cortical outcomes (cortical area fraction, cortical thickness, tissue mineral density) for PREG TEA and PREG CON were reduced (p < 0.05) following lactation but returned to the level of NONPREG CON by 2-months post-lactation, with the exception of cortical thickness. The lack of recovery of BMD and key outcomes of trabecular bone structure was unexpected. While consumption of red rooibos did not result in stronger bone post-lactation, red rooibos did support the partial recovery of trabecular BMD and bone structure following pregnancy and lactation. The findings also provide insight into the timing and dose of polyphenols to study in future interventions.

Trabecular Bone Parameters, TIMP-2, MMP-8, MMP-13, VEGF Expression and Immunolocalization in Bone and Cartilage in Newborn Offspring Prenatally Exposed to Fumonisins.

Fumonisins are protein serine/threonine phosphatase inhibitors and potent inhibitors of sphingosine N-acyltransferase (ceramide synthase) disrupting de novo sphingolipid biosynthesis. The experiment was conducted to evaluate the effects of fumonisins (FB) exposure from the 7th day of pregnancy to parturition on offspring bone development. The rats were randomly allocated to either a control group (n = 6), not treated with FBs, or to one of the two groups intoxicated with FBs (either at 60 mg FB/kg b.w. or at 90 mg FB/kg b.w. Numerous negative, offspring sex-dependent effects of maternal FB exposure were observed with regards to the histomorphometry of trabecular bone. These effects were due to FB-inducted alterations in bone metabolism, as indicated by changes in the expression of selected proteins involved in bone development: tissue inhibitor of metalloproteinases 2 (TIMP-2), matrix metalloproteinase 8 (MMP-8), matrix metalloproteinase 13 (MMP-13), and vascular endothelial growth factor (VEGF). The immunolocalization of MMPs and TIMP-2 was performed in trabecular and compact bone, as well as articular and growth plate cartilages. Based on the results, it can be concluded that the exposure of pregnant dams to FB negatively affected the expression of certain proteins responsible for bone matrix degradation in newborns prenatally exposed to FB in a dose- and sex-dependent manner.

Maternal Diet, Nutritional Status, and Birth-Related Factors Influencing Offspring's Bone Mineral Density: A Narrative Review of Observational, Cohort, and Randomized Controlled Trials.

There is growing evidence that bone health may be programmed in the first years of life. Factors during the prenatal period, especially maternal nutrition, may have an influence on offspring’s skeletal development and thus the risk of osteoporosis in further life, which is an increasing societal, health and economic burden. However, it is still inconclusive which early life factors are the most important and to what extent they may affect bone health. We searched through three databases (PubMed, Google Scholar, Cochrane Library) and after eligibility criteria were met, the results of 49 articles were analyzed. This narrative review is an overall summary of up-to-date studies on maternal diet, nutritional status, and birth-related factors that may affect offspring bone development, particularly bone mineral density (BMD). Maternal vitamin D status and diet in pregnancy, anthropometry and birth weight seem to influence BMD, however other factors such as subsequent growth may mediate these associations. Due to the ambiguity of the results in the analyzed studies, future, well-designed studies are needed to address the limitations of the present study.

The importance of maternal pregnancy vitamin D for offspring bone health: learnings from the MAVIDOS trial.

Optimisation of skeletal mineralisation in childhood is important to reduce childhood fracture and the long-term risk of osteoporosis and fracture in later life. One approach to achieving this is antenatal vitamin D supplementation. The Maternal Vitamin D Osteoporosis Study is a randomised placebo-controlled trial, the aim of which was to assess the effect of antenatal vitamin D supplementation (1000 IU/day cholecalciferol) on offspring bone mass at birth. The study has since extended the follow up into childhood and diversified to assess demographic, lifestyle and genetic factors that determine the biochemical response to antenatal vitamin D supplementation, and to understand the mechanisms underpinning the effects of vitamin D supplementation on offspring bone development, including epigenetics. The demonstration of positive effects of maternal pregnancy vitamin D supplementation on offspring bone development and the delineation of underlying biological mechanisms inform clinical care and future public-health policies.

Acrylamide-Induced Prenatal Programming of Bone Structure in Mammal Model

Abstract Acrylamide (AA) is a chemical substance with a potentially carcinogenic effect. Its presence in food or animal food arises from its thermal processing. The experiment was conducted to evaluate the effect of AA exposure (3.0 mg/kg. b.w./day) of pregnant dams during the second half of the pregnancy on bone development in offspring. As an model animal, guinea pig was used. While term body weight of newborns was not influenced by maternal AA treatment, shorter bones with reduced bone diaphysis cross-sectional area were observed in experimental group. Numerous negative, offspring sex-dependent effects of maternal AA exposure were observed in femoral epiphysis and metaphysis as well as the articular and growth plate cartilages. These effects resulted from the AA-induced alterations in bone metabolism, as indicated by the changes in the expression of numerous proteins involved in bone development: receptor activator of nuclear factor kappa-Β ligand (RANKL), tissue inhibitor of metalloproteinases 2 (TIMP-2), bone morphogenetic protein 2 (BMP-2), vascular endothelial growth factor (VEGF), and cartilage oligomeric matrix protein (COMP), all of whose expression was measured as well as distribution of immature collagen fibres was determined. Based on the results, it can be concluded that the exposure of pregnant dams to AA negatively affected the structure of compact bone in bone diaphysis, microarchitecture of trabecular bone in metaphysis and epiphysis as well as the structure of the articular and growth plate cartilages in their offspring. The AA-induced bone impairment increased osteoclast differentiation, as observed through the change in the RANKL/OPG ratio, which in turn inhibited osteoblast function by decreasing the expression of other proteins. The data of the present study suggests that maternal AA exposure can result in insufficient bone gain and even bone loss after the birth.

Dried fermented post-extraction rapeseed meal given to sows as an alternative protein source for soybean meal during pregnancy improves bone development of their offspring

The experiment was conducted to evaluate the effect of inclusion of dried fermented post-extracted rapeseed meal to the diet of pregnant sows (using 20 pregnant sows in total) on bone development in offspring. In one treatment group (n = 10 sows), the soybean meal in the diet of pregnant sows was partially replaced with dried fermented rapeseed meal (40 g/kg) during the whole pregnancy up to parturition. All newborn boars, a total of 45 in each treatment group, were grown up to the end of starter phase at the age of 77 d. Then, one boar from each sow (n = 10) was selected to be sacrificed. Dried fermented rapeseed meal included in the sow diet resulted in longer (P = 0.006) and heavier (P = 0.036) femur in their offspring. Maternal dietary supplementation of dried fermented rapeseed meal increased relative bone volume (P = 0.024) and trabecular number (P = 0.006) and decreased trabecular space (P = 0.007) in femoral epiphysis as well as increased the thickness of hyaline cartilages increased (P < 0.001). The 3-point bending test showed increase in bone mechanical strength (yield and ultimate load, stiffness, elastic energy, and work to fracture; P < 0.05) in boars maternally supplemented with dried fermented rapeseed meal. However, material properties (Young's modulus, yield, and ultimate strain) of bone did not differ between treatments, which was a result of the changes in bone mid-diaphysis's geometry. Although the quantitative indicators of bone mineralization did not differ between treatments, the maternal diet changed the structure of mineral phase of bone, as X-ray diffraction analysis shown the decrease of the mean size of the hydroxyapatite nanocrystallites (P < 0.001) in boars maternally supplemented with dried fermented rapeseed meal. This could be the effect of ionic substitutions of Ca ions in the hydroxyapatite structure, as the content of macro- and microelements in ashed bone samples was different in treatment groups. Based on the results, it can be concluded that inclusion of dried fermented rapeseed meal to the diet of pregnant sows improved the structure and mechanical properties of compact bone in the mid-diaphysis and microarchitecture of trabecular bone in metaphysis and epiphysis of the examined bones in their offspring at the beginning of the grower period.

Maternal Bisphenol A exposure impaired endochondral ossification in craniofacial cartilage of rare minnow (Gobiocypris rarus) offspring

Bisphenol A (BPA), an endocrine disrupting compound, is present in the aquatic environment. BPA can mimic estrogen and cause adverse effects on development and reproduction in different organisms. As epigenetic modifications due to BPA exposure have been reported, the interest on the effects of this chemical has increased. To assess the potential effects of maternal BPA exposure on offspring bone development, adult Gobiocypris rarus (G. rarus) females were exposed to 15 μg L−1 and 225 μg L−1 BPA for 21 days. Eggs were collected after artificial spawning and fertilized with the fresh milt of non-exposed male fish. The offspring were raised in clean water and randomly selected for examination at different development stages. Our results showed that specific effects including poor quality of the embryos, increased malformation (bent spine and tail), and delayed craniofacial cartilage ossification of the larvae. Additionally, the transcripts of ossification related genes were significantly downregulated in offspring, and the lysyloxidase activity decreased. The present study demonstrated the maternal-mediated skeleton toxicity of BPA and its adverse effects on G. rarus.

Maternal serum retinol and β-carotene concentrations and neonatal bone mineralization: results from the Southampton Women’s Survey cohort

Background: Studies in older adults and animals have suggested contrasting relations between bone health and different vitamin A compounds. To our knowledge, the associations between maternal vitamin A status and offspring bone development have not previously been elucidated.Objective: We examined the associations between maternal serum retinol and β-carotene concentrations during late pregnancy and offspring bone mineralization assessed at birth with the use of dual-energy X-ray absorptiometry.Design: In the Southampton Women’s Survey mother-offspring birth cohort, maternal health, lifestyle, and diet were assessed prepregnancy and at 11 and 34 wk of gestation. In late pregnancy, maternal serum retinol and β-carotene concentrations were measured. Offspring total body bone mineral density (BMD), bone mineral content (BMC), and bone area (BA) were measured within 2 wk after birth.Results: In total, 520 and 446 mother-offspring pairs had measurements of maternal serum retinol and β-carotene, respectively. Higher maternal serum retinol in late pregnancy was associated with lower offspring total body BMC (β = −0.10 SD/SD; 95% CI: −0.19, −0.02; P = 0.020) and BA (β = −0.12 SD/SD; 95% CI: −0.20, −0.03; P = 0.009) but not BMD. Conversely, higher maternal serum β-carotene concentrations in late pregnancy were associated with greater total body BMC (β = 0.12 SD/SD; 95% CI: 0.02, 0.21; P = 0.016) and BA (β = 0.12 SD/SD; 95% CI: 0.03, 0.22; P = 0.010) but not BMD.Conclusions: Maternal serum retinol and β-carotene concentrations had differing associations with offspring bone size and growth at birth: retinol was negatively associated with these measurements, whereas β-carotene was positively associated. These findings highlight the need for further investigation of the effects of maternal retinol and carotenoid status on offspring bone development.

Maternal High Fat Diet Affects Offspring's Vitamin K-Dependent Proteins Expression Levels.

Studies suggest bone growth & development and susceptibility to vascular disease in later life are influenced by maternal nutrition, during intrauterine and early postnatal life. There is evidence for a role of vitamin K-dependent proteins (VKDPs) including Osteocalcin, Matrix-gla protein, Periostin, and Gas6, in bone and vascular development. This study extends the analysis of VKDPs previously conducted in 6 week old offspring, into offspring of 30 weeks of age, to assess the longer term effects of a maternal and postnatal high fat (HF) diet on VKDP expression. Overall a HF maternal diet and offspring diet exacerbated the bone changes observed. Sex specific and tissue specific differences were observed in VKDP expression for both aorta and femoral tissues. In addition, significant correlations were observed between femoral OCN, Periostin Gas6, and Vkor expression levels and measures of femoral bone structure. Furthermore, MGP, OCN, Ggcx and Vkor expression levels correlated to mass and fat volume, in both sexes. In summary the current study has highlighted the importance of the long-term effects of maternal nutrition on offspring bone development and the correlation of VKDPs to bone structure.

Maternal high-fat diet and offspring expression levels of vitamin K-dependent proteins.

Studies suggest that bone growth and development and susceptibility to vascular disease in later life are influenced by maternal nutrition during intrauterine and early postnatal life. There is evidence for a role of vitamin K-dependent proteins (VKDPs) including osteocalcin, matrix Gla protein, periostin, and growth-arrest specific- protein 6, in both bone and vascular development. We have examined whether there are alterations in these VKDPs in bone and vascular tissue from offspring of mothers subjected to a nutritional challenge: a high-fat diet during pregnancy and postnatally, using 6-week-old mouse offspring. Bone site-specific and sex-specific differences across femoral and vertebral bone in male and female offspring were observed. Overall a high-fat maternal diet and offspring diet exacerbated the bone changes observed. Sex-specific differences and tissue-specific differences were observed in VKDP levels in aorta tissue from high-fat diet-fed female offspring from high-fat diet-fed mothers displaying increased levels of Gas6 and Ggcx compared with those of female controls. In contrast, differences were seen in VKDP levels in femoral bone of female offspring with lower expression levels of Mgp in offspring of mothers fed a high-fat diet compared with those of controls. We observed a significant correlation in Mgp expression levels within the femur to measures of bone structure of the femur and vertebra, particularly in the male offspring cohort. In summary, the current study has highlighted the importance of maternal nutrition on offspring bone development and the correlation of VKDPs to bone structure.

Prenatal calcium and vitamin D intake, and bone mass in later life.

The aging population will result in an increasing burden of osteoporotic fractures, necessitating the identification of novel strategies for prevention. There is increasing recognition that factors in utero may influence bone mineral accrual, and, thus, osteoporosis risk. The role of calcium and vitamin D has received much attention in recent years, and in this review, we will survey available studies relating maternal calcium and vitamin D status during pregnancy to offspring bone development. The evidence base supporting a positive influence on intrauterine skeletal growth appears somewhat stronger for maternal 25(OH)-vitamin D concentration than for calcium intake, and the available data point toward the need for high-quality randomized controlled trials in order to inform public health policy. It is only with such a rigorous approach that it will be possible to delineate the optimal strategy for vitamin D supplementation in pregnancy in relation to offspring bone health.

Impact of Maternal Prenatal Stress on Growth of the Offspring

Unperturbed fetal development is essential for future health of an individual. Previous studies have linked diseases of aging to harmful alterations that happen during fetal development. Given the significant long-term impact that intrauterine environment has on an individual's life, it was hypothesized that maternal stress during pregnancy will have negative effects on the offspring's prenatal and postnatal growth. To test this, twenty-eight female and seven male Wistar rats (Rattus norvegicus) were purchased and bred to produce 176 offspring. During pregnancy, dams were randomly divided into four groups (n=7, per group) and immobilization stress induced as follows; Group 1 (GW1): immobilization stress on days 1-7 of pregnancy, Group 2 (GW2): on days 8-14, Group 3 (GW3): on days 15-21, Group 4 (Controls): left undisturbed. Maternal cortisol hormone, food intake, and weight gain were monitored during pregnancy. Pups were raised under normal laboratory conditions and sacrificed at ages: 4, 8, 12, and 16 weeks to determine the effect of prenatal stress. At necropsy, the tibia was removed and processed for histology. Differences among groups were determined by T-test or analysis of variance (ANOVA). Linear regression analysis was performed to establish the relationship between stress in utero and indicators of bone development in offspring. P values ≤ 0.05 were considered significant. Cortisol hormone levels in controls were lower than those of stressed animals. Stressed dams consumed 12.5% less food per day compared to controls. Animals in GW1 and GW2 gained less weight during pregnancy but had larger litters than did GW3 or the control group. Offspring born to GW3 were heavier compared to all other groups. GW3 offspring had a higher rate of bone formation. In conclusion, stress during pregnancy resulted in increased cortisol and reduced food intake in mothers, but faster growth and higher weight gain in offspring compared to controls.

Effects of Maternal Hypoxia during Pregnancy on Bone Development in Offspring: A Guinea Pig Model.

Low birth weight is associated with reduced bone mass and density in adult life. However, effects of maternal hypoxia (MH) on offspring bone development are not known. Objective. The current study investigated the effects of fetal growth restriction induced by MH during the last half of gestation on bone structure and volume in the offspring of the fetus near term and the pup in adolescence. Methods. During 35–62-day gestation (term, 69d), guinea pigs were housed in room air (21% O2; control) or 12% O2 (MH). Offspring femur and tibia were collected at 62d gestation and 120d after birth. Results. MH decreased fetal birth weight but did not affect osteogenic potential pools in the fetal bone marrow. Histological analysis showed no effects of MH on tibial growth plate thickness in either fetal or postnatal offspring, although there was increased VEGF mRNA expression in the growth plate of postnatal offspring. MH did not change primary spongiosa height but lowered collagen-1 mRNA expression in postnatal offspring. There was increased mRNA expression of adipogenesis-related gene (FABP4) in bone from the MH postnatal offspring. Conclusion. MH during late gestation did not change the pool of osteogenic cells before birth or growth plate heights before and after birth. However, MH reduced expression of bone formation marker (collagen-1) and increased expression of fat formation marker (FABP4) in postnatal offspring bone.

Maternal Antenatal Vitamin D Status and Offspring Muscle Development: Findings From the Southampton Women's Survey

Maternal 25-hydroxyvitamin D [25(OH)D] status in pregnancy has been associated with offspring bone development and adiposity. Vitamin D has also been implicated in postnatal muscle function, but little is known about a role for antenatal 25(OH)D exposure in programming muscle development. We investigated the associations between maternal plasma 25(OH)D status at 34 weeks of gestation and offspring lean mass and muscle strength at 4 years of age. We studied a prospective UK population-based mother-offspring cohort: the Southampton Women's Survey (SWS). Initially, 12,583 nonpregnant women were recruited into the SWS, of whom 3159 had singleton pregnancies; 678 mother-child pairs were included in this analysis. At 4 years of age, offspring assessments included hand grip strength and whole-body dual-energy x-ray absorptiometry, yielding lean mass and percent lean mass. Physical activity was assessed by 7-day accelerometry in a subset of children (n=326). The maternal serum 25(OH)D concentration in pregnancy was positively associated with offspring height-adjusted hand grip strength (β=0.10 SD/SD, P=.013), which persisted after adjustment for maternal confounding factors, duration of breastfeeding, and child's physical activity at 4 years (β=0.13 SD/SD, P=.014). Maternal 25(OH)D was also positively associated with offspring percent lean mass (β=0.11 SD/SD, P=.006), but not total lean mass (β=0.06 SD/SD, P=.15). However, this association did not persist after adjustment for confounding factors (β=0.09 SD/SD, P=.11). This observational study suggests that intrauterine exposure to 25(OH)D during late pregnancy might influence offspring muscle development through an effect primarily on muscle strength rather than on muscle mass.

Maternal vitamin D status in pregnancy and offspring bone development: the unmet needs of vitamin D era

Data from animal and human studies implicate maternal vitamin D deficiency during pregnancy as a significant risk factor for several adverse outcomes affecting maternal, fetal, and child health. The possible associations of maternal vitamin D status and offspring bone development comprise a significant public health issue. Evidence from randomized trials regarding maternal vitamin D supplementation for optimization of offspring bone mass is lacking. In the same field, data from observational studies suggest that vitamin D supplementation is not indicated. Conversely, supplementation studies provided evidence that vitamin D has beneficial effects on neonatal calcium homeostasis. Nevertheless, a series of issues, such as technical difficulties of current vitamin D assays and functional interplay among vitamin D analytes, prohibit arrival at safe conclusions. Future studies would benefit from adoption of a gold standard assay, which would unravel the functions of vitamin D analytes. This narrative review summarizes and discusses data from both observational and supplementation studies regarding maternal vitamin D status during pregnancy and offspring bone development.

Neonatal knee ultrasound: a new method for assessing distal femur morphology in perinatal vitamin D insufficiency

Event Abstract Back to Event Neonatal knee ultrasound: a new method for assessing distal femur morphology in perinatal vitamin D insufficiency PA Mahon1*, G Ntani1, C Cooper2, KM Godfrey3, MK Javaid2 and NC Harvey1 1 University of Southampton, MRC Lifecourse Epidemiology Unit, United Kingdom 2 Oxford NIHR Musculoskeletal Biomedical Research Centre, Oxford NIHR Musculoskeletal Biomedical Research Centre, United Kingdom 3 Southampton General Hospital, NIHR Nutrition, Diet and Lifestyle Biomedical Research Unit, United Kingdom We have previously demonstrated that lower maternal circulating 25(OH)-vitamin D concentrations in late pregnancy are associated with reduced offspring bone mass postnatally, and altered distal femoral morphology in utero, reminiscent of metaphyseal changes observed in postnatal rickets. We therefore aimed to develop a technique that would allow investigation of whether distal femoral morphology differed in offspring born to women who were supplemented with vitamin D or placebo in a randomised, double-blind, placebo-controlled trial (MAVIDOS: Maternal Vitamin D Osteoporosis Study).{BR}Pregnant women recruited to the MAVIDOS study at their 11 week nuchal or dating scan are randomised to either 1000 IU cholecalciferol daily or matched placebo until delivery of the baby. Fetal measurements are taken using ultrasound at 11, 19 and 34 weeks gestation, with dual energy X-ray absorptiometry of the neonate at birth. From the 400 pregnant women recruited to date a sub-set of 142 neonates underwent 3D ultrasound assessment of the distal femoral metaphysis within 2 weeks after delivery. Measurements of epiphyseal volume (using VOCAL technique), central epiphyseal-metaphyseal distance (CEMD) and cross-sectional area (CSA) were taken in triplicate from stored images. Values were adjusted for gestational age and then assessed for reproducibility. The coefficients of variation (CVs) were 0.98% for linear CEMD, 0.83% for epiphyseal volume and 2.17% for traced CSA measurements. These results demonstrate good reproducibility. Additionally, the between-subject variability was assessed and showed a sizeable range of dimensions consistent with biological variation: between subject CVs for CEMD, epiphyseal volume and CSA were 28.7%, 49.4% and 17.3%, respectively.{BR}These results suggest that the technique is reproducible and may yield meaningful biological data. Images on further participants will be acquired and at the end of the trial, comparisons will be made of measurements in babies of supplemented and unsupplemented mothers. Potentially, this will add valuable information regarding the role of maternal vitamin D status in offspring bone development. This non-invasive technique may also be utilised in longitudinal assessments during childhood follow-up studies, allowing the longer term evaluation of effects originating in utero. Keywords: Bones, Bone Research Conference: 2011 joint meeting of the Bone Research Society & the British Orthopaedic Research Society, Cambridge, United Kingdom, 27 Jun - 29 Jun, 2011. Presentation Type: Poster Topic: Abstracts Citation: Mahon P, Ntani G, Cooper C, Godfrey K, Javaid M and Harvey N (2011). Neonatal knee ultrasound: a new method for assessing distal femur morphology in perinatal vitamin D insufficiency. Front. Endocrinol. Conference Abstract: 2011 joint meeting of the Bone Research Society & the British Orthopaedic Research Society. doi: 10.3389/conf.fendo.2011.02.00043 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Sep 2011; Published Online: 30 Sep 2011. * Correspondence: Dr. PA Mahon, University of Southampton, MRC Lifecourse Epidemiology Unit, United Kingdom, pam@mrc.soton.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers PA Mahon G Ntani C Cooper KM Godfrey MK Javaid NC Harvey Google PA Mahon G Ntani C Cooper KM Godfrey MK Javaid NC Harvey Google Scholar PA Mahon G Ntani C Cooper KM Godfrey MK Javaid NC Harvey PubMed PA Mahon G Ntani C Cooper KM Godfrey MK Javaid NC Harvey Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.