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Osteogenic potential of osteoblasts from neonatal rats born to mothers treated with caffeine throughout pregnancy.

ABSTRACT: Caffeine is an active alkaloid that can cause damage to bones in formation during prenatal life into adulthood. This compound can pass across the placenta and into the mother's milk, causing a reduction in bone formation, growth and mass. The objective of this study was to examine the osteogenic potential of osteoblasts extracted from neonatal rats born to mothers treated with caffeine throughout pregnancy.Twenty-four adult Wistar rats were randomly divided into four groups, consisting of one control group and three groups that were treated with 25, 50, or 100 mg/kg of caffeine by an oral-gastric probe throughout the duration of the experimental period (pregnancy). At birth, three puppies from each dam in each group were euthanized, and osteoblasts were extracted from the calvaria of these pups for in vitro testing.The osteoblasts extracted from the pups of rats that received 50 mg/kg caffeine during pregnancy exhibited increased expression of osteocalcin, osteopontin, sialoprotein, runx-2, alkaline phosphatase and type I collagen transcripts, resulting in increased synthesis of mineralization nodules.Neonates from rats treated with 50 mg/kg caffeine during pregnancy contained osteoblasts with a higher osteogenic potential characterized by increased expression of osteocalcin, osteopontin, sialoprotein, runx-2, alkaline phosphatase and type I collagen and increased synthesis of mineralization nodules.

SUBMITTER: Reis AM

PROVIDER: S-EPMC4324429 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Osteogenic potential of osteoblasts from neonatal rats born to mothers treated with caffeine throughout pregnancy.

Reis Amanda Maria Sena AM Ribeiro Lorena Gabriela Rocha LG Ocarino Natália de Melo Nde M Goes Alfredo Miranda AM Serakides Rogéria R

BMC musculoskeletal disorders 20150204

<h4>Background</h4>Caffeine is an active alkaloid that can cause damage to bones in formation during prenatal life into adulthood. This compound can pass across the placenta and into the mother's milk, causing a reduction in bone formation, growth and mass. The objective of this study was to examine the osteogenic potential of osteoblasts extracted from neonatal rats born to mothers treated with caffeine throughout pregnancy.<h4>Methods</h4>Twenty-four adult Wistar rats were randomly divided int ...[more]

PMID: 25649420

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Project description:BackgroundMaternal asthma is associated with serious pregnancy complications, but newborn morbidity is understudied.ObjectiveWe wanted to determine whether infants of asthmatic mothers have more neonatal complications.MethodsThe Consortium on Safe Labor (2002-2008), a retrospective cohort, included 223,512 singleton deliveries at ? 23 weeks' gestation. Newborns of mothers with asthma (n = 17,044) were compared with newborns of women without asthma by using logistic regression models with generalized estimating equations to calculate adjusted odds ratios (ORs) and 95% CIs. Electronic medical record data included gestational week at delivery, birth weight, resuscitation, neonatal intensive care unit (NICU) admission, NICU length of stay, hyperbilirubinemia, respiratory distress syndrome, apnea, sepsis, anemia, transient tachypnea of the newborn, infective pneumonia, asphyxia, intracerebral hemorrhage, seizure, cardiomyopathy, periventricular or intraventricular hemorrhage, necrotizing enterocolitis, aspiration, retinopathy of prematurity, and perinatal mortality.ResultsPreterm delivery was associated with maternal asthma for each week after 33 completed weeks of gestation and not earlier. Maternal asthma also increased the adjusted odds of small for gestational age (OR = 1.10; 95% CI, 1.05-1.16), NICU admission (OR = 1.12; 95% CI, 1.07-1.17), hyperbilirubinemia (OR = 1.09; 95% CI, 1.04-1.14), respiratory distress syndrome (OR = 1.09; 95% CI, 1.01-1.19), transient tachypnea of the newborn (OR = 1.10; 95% CI, 1.02-1.19), and asphyxia (OR = 1.34; 95% CI, 1.03-1.75). Findings persisted for term infants (? 37 weeks) who had additional increased odds of intracerebral hemorrhage (OR = 1.84; 95% CI, 1.11-3.03) and anemia (OR = 1.30; 95% CI, 1.04-1.62).ConclusionsMaternal asthma was associated with prematurity and small for gestational age. Adverse neonatal outcomes, including respiratory complications, hyperbilirubinemia, and NICU admission, were increased in association with maternal asthma even among term deliveries.

Project description:Objectives:To investigate the association between the mode of birth and adverse neonatal outcomes of macrosomic (birth weight ?4000?g) and non-macrosomic (birth weight <4000?g) live-born term singletons in vertex presentation (TSV) born to mothers with diabetes (pre-existing and gestational diabetes mellitus (GDM)). Design:A population-based retrospective cohort study. Setting:New South Wales, Australia. Patients:All live-born TSV born to mothers with diabetes from 2002 to 2012. Intervention:Comparison of neonatal outcomes by mode of birth (prelabour caesarean section (CS) and planned vaginal birth resulted in intrapartum CS, non-instrumental or instrumental vaginal birth). Main outcome measures:Five-minute Apgar score <7, admission to neonatal intensive care unit (NICU) or special care nursery (SCN) and the need for resuscitation. Results:Among the 48 882 TSV born to mothers with diabetes, prelabour CS was associated with a significant increase in the rate of admission to NICU/SCN compared with planned vaginal birth.For TSV born to mothers with pre-existing diabetes, compared with non-instrumental vaginal birth, instrumental vaginal birth was associated with increased odds of the need for resuscitation in macrosomic (adjusted ORs (AOR) 2.6; 95% CI (1.2 to 7.5)) and non-macrosomic TSV (AOR 3.3; 95%?CI (2.2 to 5.0)).For TSV born to mothers with GDM, intrapartum CS was associated with increased odds of the need for resuscitation compared with non-instrumental vaginal birth in non-macrosomic TSV (AOR 2.3; 95%?CI (2.1 to 2.7)). Instrumental vaginal birth was associated with increased likelihood of requiring resuscitation compared with non-instrumental vaginal birth for both macrosomic (AOR 2.3; 95%?CI (1.7 to 3.1)) and non-macrosomic (AOR 2.5; 95%?CI (2.2 to 2.9)) TSV. Conclusion:Pregnant women with diabetes, particularly those with suspected fetal macrosomia, need to be aware of the increased likelihood of adverse neonatal outcomes following instrumental vaginal birth and intrapartum CS when planning mode of birth.

Project description:BackgroundPreterm birth implies an array of respiratory diseases including apnea of prematurity and bronchopulmonary dysplasia (BPD). Caffeine has been introduced to treat apneas but also appears to reduce rates of BPD. Oxygen is essential when treating preterm infants with respiratory problems but high oxygen exposure aggravates BPD. This experimental study is aimed at investigating the action of caffeine on inflammatory response and cell death in pulmonary tissue in a hyperoxia-based model of BPD in the newborn rat. Material/Methods. Lung injury was induced by hyperoxic exposure with 80% oxygen for three (P3) or five (P5) postnatal days with or without recovery in ambient air until postnatal day 15 (P15). Newborn Wistar rats were treated with PBS or caffeine (10 mg/kg) every two days beginning at the day of birth. The effects of caffeine on hyperoxic-induced pulmonary inflammatory response were examined at P3 and P5 immediately after oxygen exposure or after recovery in ambient air (P15) by immunohistological staining and analysis of lung homogenates by ELISA and qPCR.ResultsTreatment with caffeine significantly attenuated changes in hyperoxia-induced cell death and apoptosis-associated factors. There was a significant decrease in proinflammatory mediators and redox-sensitive transcription factor NFκB in the hyperoxia-exposed lung tissue of the caffeine-treated group compared to the nontreated group. Moreover, treatment with caffeine under hyperoxia modulated the transcription of the adenosine receptor (Adora)1. Caffeine induced pulmonary chemokine and cytokine transcription followed by immune cell infiltration of alveolar macrophages as well as increased adenosine receptor (Adora1, 2a, and 2b) expression.ConclusionsThe present study investigating the impact of caffeine on the inflammatory response, pulmonary cell degeneration and modulation of adenosine receptor expression, provides further evidence that caffeine acts as an antioxidative and anti-inflammatory drug for experimental oxygen-mediated lung injury. Experimental studies may broaden the understanding of therapeutic use of caffeine in modulating detrimental mechanisms involved in BPD development.

Project description:Recent research shows that preschool children born to opioid-dependent mothers are at increased risk for cognitive, psychomotor, attention, and social-emotional adjustment problems. But very little is known about their school-age functioning, particularly their educational achievement. This analysis examined the educational outcomes of a regional cohort of 100 prenatally methadone-exposed children who were prospectively studied from birth to age 9.5 years alongside a comparison group of 110 randomly identified non-exposed children born between 2003 and 2008. At age 9.5, as part of a comprehensive neurodevelopmental evaluation, children's teachers rated their achievement across the school curriculum, and children completed the Woodcock Johnson-III Tests of Achievement (WJ-III). Detailed information about the birth mother's social background, pregnancy substance use, and mental health was also collected during pregnancy/at term. Infant clinical data were collected after birth. Methadone-exposed children performed less well than non-exposed children across seven school curriculum areas rated by teachers (ps ?.001), performed less well than non-exposed children on all reading and mathematics subtests of the WJ-III, and had higher rates of any educational delay on the WJ-III (57% vs. 15%), OR = 7.47 (3.71-15.02). Results were similar when children with severe intellectual impairment were excluded. After adjusting for confounding factors, methadone-exposed children had increased odds of educational delay, but this was only marginally significant (OR = 3.62, [1.01-13.01], p = .049). Maternal educational attainment level (OR = 0.69, [0.50-0.89], p = .006), and maternal benzodiazepine use during pregnancy (OR = 2.70 [1.03-7.12], p = .044) were also associated with later educational risk. Findings suggest that children born to opioid-dependent women enrolled in methadone maintenance are at high risk of educational delay by age 9.5 years. Children's academic difficulties appeared to reflect the effects of both adverse prenatal exposures and postnatal social risk.

Project description:BackgroundFormate can be incorporated into 10-formyl-tetrahydrofolate (10-formyl-THF), which is a substrate for purine synthesis, and after further reduction of the one-carbon group, may be used as a substrate for thymidylate synthesis and for homocysteine remethylation.ObjectiveWe examined plasma formate concentrations and the expression of genes involved in the production and utilization of formate in fetal and neonatal rats and in pregnant and virgin female rats.MethodsIn 1 experiment, plasma formate was measured by GC-MS in rats aged 1-56 d. In a second experiment, virgin female (adult) rats, 19-d pregnant rats (P) and their male and female fetuses (F), and 3-d-old (N) and 7-d-old (J) offspring had plasma and amniotic fluid analyzed for formate by GC-MS, mRNA abundance in liver and placenta by qPCR, and several plasma amino acids by HPLC.ResultsThe plasma formate concentration was significantly higher in fetuses at embryonic day 19 than in the mothers. It was also significantly higher in neonatal rats but slowly returned to adult concentrations by ∼3 wk. The abundance of mitochondrial monofunctional 10-formyl-tetrahydrofolate synthetase (Mthfd1l) mRNA was significantly higher in placenta (PP) and F liver than in liver of N or J. Expression of mitochondrial bifunctional NAD-dependent methylene-tetrahydrofolate dehydrogenase/methenyl-tetrahydrofolate cyclohydrolase (Mthfd2) was significantly enriched in PP and liver of P, intermediate in F liver, and much lower in liver of N and J, relative to PP. Serine hydroxymethyltransferase 2 (Shmt2), methylenetetrahydrofolate dehydrogenase 1 (Mthfd1), and glycine decarboxylase protein of the glycine cleavage system (Gldc) mRNA expression was significantly lower in PP compared with other groups. Cytoplasmic NAD(P)-dependent 10-formyl-tetrahydrofolate dehydrogenase (Aldh1/1) and mitochondrial NAD(P)-dependent 10-formyl-tetrahydrofolate dehydrogenase (Aldh1/2) , genes responsible for the catabolism of 10-formylTHF, were very weakly expressed in PP, low in livers of F and N, and reached the significantly higher adult levels in J. Serine, glycine, and methionine concentrations in plasma of F were significantly higher than in plasma of P.ConclusionsFormate metabolism is highly active in fetuses and in placenta of pregnant rats.

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Osteogenic potential of osteoblasts from neonatal rats born to mothers treated with caffeine throughout pregnancy.

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Osteogenic potential of osteoblasts from neonatal rats born to mothers treated with caffeine throughout pregnancy.

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