RESUMO
Apolipoprotein E (APOE) is a major cholesterol carrier responsible for lipid transport and injury repair in the brain. The human APOE gene (h-APOE) has 3 naturally occurring alleles: ε3, the common allele; ε4, which increases Alzheimer's disease (AD) risk up to 15-fold; and ε2, the rare allele which protects against AD. Although APOE4 has negative effects on neurocognition in old age, its persistence in the population suggests a survival advantage. We investigated the relationship between APOE genotypes and fertility in EFAD mice, a transgenic mouse model expressing h-APOE. We show that APOE4 transgenic mice had the highest level of reproductive performance, followed by APOE3 and APOE2. Intriguingly, APOE3 pregnancies had more fetal resorptions and reduced fetal weights relative to APOE4 pregnancies. In conclusion, APOE genotypes impact fertility and pregnancy outcomes in female mice, in concordance with findings in human populations. These mouse models may help elucidate how h-APOE4 promotes reproductive fitness at the cost of AD in later life.
Assuntos
Doença de Alzheimer , Apolipoproteínas E , Modelos Animais de Doenças , Fertilidade , Camundongos Transgênicos , Animais , Doença de Alzheimer/genética , Feminino , Camundongos , Fertilidade/genética , Humanos , Apolipoproteínas E/genética , Apolipoproteína E4/genética , Polimorfismo Genético , Gravidez , Genótipo , Apolipoproteína E3/genética , AlelosRESUMO
Iron deficiency (ID) in utero and in infancy can cause irreversible neurocognitive damage. Iron status is not routinely tested at birth, so the burden of neonatal ID in the United States is unknown. Infants born from twin or higher-order pregnancies may be at elevated risk of inadequate nutrient endowment at birth. The present study sought to compare the burden of neonatal ID in cord blood serum samples from twin (n = 54) and singleton pregnancies (n = 24). Iron status (serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin) and inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) biomarker concentrations were measured by immunoassay. The prevalence of ID (SF < 76 ng/mL) among twins was 21% (23/108) and among singletons 20% (5/24). Gestational age at birth, maternal race and infant sex predicted SF levels. Maternal anemia (hemoglobin < 11 g/dL) was observed in 40% of mothers but was not associated with neonatal iron biomarkers. More research is needed to identify risk factors and regulatory mechanisms for inadequate fetal iron accrual to identify higher risk pregnancies and neonates for screening and intervention.