Abstract
BackgroundMaternal stress during pregnancy is one of the major adverse environmental factors in utero that is capable of influencing health outcomes of the offspring throughout life. Both genetic and epigenetic processes are susceptible to environmental insults in utero and are potential biomarkers of the experienced environment including maternal stress.MethodsWe profiled expression level of six genes in hypothalamic pituitary adrenal (HPA) axis functioning (HSD11B2, SLC6A4, NR3C1, NR3C2, CRHR1 and CRHR2), two imprinted genes (IGF2 and H19) and one neurodevelopmental gene (EGR1), from 49 pairs of placenta and umbilical cord blood (UCB) samples from a birth cohort. We also assessed global methylation levels by LUminometric Methylation Assay (LUMA) and methylation at the imprinting control region (ICR) of IGF2/H19.ResultsLittle correlations between paired placenta and UCB were observed except H19 expression (r = 0.31, P = 0.04) and IGF2/H19 ICR methylation (r = 0.43, P = 0.01); gene expression levels were significantly higher (P < 0.001) in placenta than UCB except CRHR1 and CRHR2, which were unexpressed in placenta. Maternal stress correlated higher levels of HPA genes and lower levels of EGR1 and LUMA, but only in placenta. Positive association between maternal stress and IGF2/H19 ICR methylation was present in both placenta and UCB.ConclusionsOur findings support the notion that adverse in utero environment, as measured by antenatal maternal stress, depression and anxiety, can be observed in the epi/genome of the relevant tissues, i.e. placenta and UCBs, leading to development of molecular markers for assessing in utero adversities.
Highlights
Increasing evidence suggests that the period of intrauterine development constitutes one of the most critical periods that can influence risks for neurodevelopmental and mental disease of the offspring throughout life
Little correlations between paired placenta and umbilical cord blood (UCB) were observed except H19 expression (r = 0.31, P = 0.04) and IGF2/H19 imprinting control region (ICR) methylation (r = 0.43, P = 0.01); gene expression levels were significantly higher (P < 0.001) in placenta than UCB except CRHR1 and CRHR2, which were unexpressed in placenta
Positive association between maternal stress and IGF2/H19 ICR methylation was present in both placenta and UCB
Summary
Increasing evidence suggests that the period of intrauterine development constitutes one of the most critical periods that can influence risks for neurodevelopmental and mental disease of the offspring throughout life. Placenta is the first complex fetal organ to form during development Once developed it serves as the source of fetal nutrients, water, gas exchange, excretion, and immune regulation. It shares integrated endocrine control with the brain and may play a vital role in fetal growth and neurodevelopment. Maternal stress during pregnancy is one of the major adverse environmental factors in utero that is capable of influencing health outcomes of the offspring throughout life. Both genetic and epigenetic processes are susceptible to environmental insults in utero and are potential biomarkers of the experienced environment including maternal stress
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