Objective One in 3 pregnant women in the United States is
Objective One in 3 pregnant women in the United States is obese. as early as the second trimester. These findings may have implications for postnatal neurodevelopmental and metabolic abnormalities described in the offspring of obese women. Introduction Maternal 942999-61-3 supplier obesity is a major public health problem in the United States. Sixty percent of reproductive age women are overweight at conception and one third are obese , . There has been a parallel rise in childhood obesity and metabolic syndrome. This has coincided with an increased interest in the impact of the intrauterine environment on fetal gene expression and development . Offspring of obese parents are significantly more likely to be obese and to have metabolic syndrome , . Importantly, maternal body mass index (BMI) is more significantly associated with offspring obesity than paternal BMI, suggesting that the environment plays an important role . Maternal obesity also seems to have intergenerational health consequences beyond childhood metabolic obesity and symptoms. Data from huge epidemiologic studies recommend a link with undesirable neurodevelopmental results in offspring, including lower general cognitive features , , , and an elevated occurrence of autism range disorders , developmental hold off , and interest deficit hyperactivity disorder . The molecular systems where maternal weight problems may bring about an elevated risk for years as a child weight problems, metabolic symptoms, and adverse neurodevelopmental outcomes are unfamiliar currently. Amniotic liquid supernatant (AFS) gives exclusive advantages in learning real-time human being fetal physiology and advancement. The evaluation of cell-free fetal RNA (cffRNA) in AFS employs a easily available, discarded human biofluid typically. Prior function by our lab has proven that fetal gene manifestation patterns in AFS differ relating to gender, gestational age group, and disease condition , , , , . Cell-free fetal nucleic acids can be found in higher concentrations in amniotic liquid considerably, and occur from a definite pool, in ICAM1 comparison to cell-free nucleic acids in maternal serum , , , . While cell-free fetal RNA and DNA in maternal serum are recognized to occur through the placenta , , , , epigenetic research and gene manifestation microarrays of cell-free fetal nucleic acids in amniotic liquid demonstrate relatively small contribution through the placenta , . Therefore, cell-free nucleic acids in amniotic liquid provide real-time information regarding fetal advancement. Characterization of the standard second trimester amniotic liquid core transcriptome offers proven cffRNA transcripts in mid-trimester amniotic liquid reflecting the introduction of multiple organs like the fetal thyroid, liver organ, lung, pancreas, bloodstream, and mind . In prior function from our group, twenty-three organ-specific transcripts had been determined extremely, one-third which mapped towards the fetal mind . This unpredicted and book locating continues to be substantiated in later on research , and suggests that amniotic fluid supernatant may be used to obtain neurodevelopmental information from living fetuses. These nucleic acid transcripts may pass into amniotic fluid via transport through fetal membranes in the fontanelle, nose, or ear; via shedding through urine; the trachea; fetal blood, or other mechanisms. Here, we performed a discovery-driven research study to test the hypothesis that fetuses of obese women have different gene expression patterns than fetuses of lean women. We used cell-free RNA isolated from second trimester amniotic fluid supernatant, gene expression microarrays, and publicly available bioinformatics resources to identify differentially expressed genes, and 942999-61-3 supplier their 942999-61-3 supplier functions and interactions. In so doing, we have identified mechanisms that may be associated with an increased risk of neurodevelopmental and metabolic morbidity in offspring of obese pregnant women. Materials and Methods Ethics statement Samples were collected with approval from the Tufts Medical Center Institutional Review Board from June 2011 through April 2012 (IRB protocol # 5582). Subjects signed informed consent for amniocentesis, which was performed for standard clinical indications. Recruitment and sample collection This was a prospective pilot study of women with singleton fetuses without structural anomalies going through second trimester (14C24 weeks) hereditary amniocentesis at Tufts INFIRMARY. Subjects signed educated consent for amniocentesis, that was performed for regular clinical signs (advanced maternal age group, ultrasonographic smooth markers of aneuploidy, irregular serum screening outcomes, or maternal demand). Women having a BMI30 (obese, n?=?14) or <25 (low 942999-61-3 supplier fat, n?=?23) during amniocentesis were enrolled. Per process, usage of the medical record was limited by clinical information offered by enough time of amniocentesis (i.e. signs for the task, presence/lack of fetal anomalies, regular maternal demographic data), and cytogenetic outcomes. Fetuses later on discovered with an irregular karyotype, or those with RNA or cDNA of insufficient quality or quantity to hybridize to.