Noncoding RNA regulation of the human placental transcriptome among the sexes

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Abstract The placenta, critical for fetal health and development and a potential marker of maternal health, is poorly understood. Traditionally, studies of human placental function have focused on samples obtained at term, limiting our ability to understand both normal placental development and function throughout human gestation. The development of conditions and diseases which manifest throughout pregnancy attributed to placental development and subsequently function most likely occur early in gestation. Early direct placental assessment can be achieved through chorionic villus sampling (CVS), performed in the late first trimester. These villi, used for cytogenetic testing, also represent a unique window into the developing placenta. We developed techniques to bank unused villi for use in subsequent multiple –omics testing including genomics, epigenomics and transcriptomics and also collect term placental samples from these pregnancies providing a window into placental development and potential function throughout gestation. Recently, we identified sex differences in a number of genes expressed on autosomes and sex chromosomes in the first trimester placenta, unique from those identified at term, suggesting there are sex differences in placental development as early as the first trimester. In addition, we also identified differences in noncoding RNA fractions among the sexes, expressed from both autosomes and sex chromosomes. As these noncoding RNA’s are important regulators of transcriptional activity and hence overall function, they may explain the more subtle sex differences observed in fetal development and disease as a result of placental development. However, sexual dimorphism of gene regulation through noncoding RNA has not been studied in normal placental development. Thus, using our already stored samples and our genomics bioinformatics expertise, we have the opportunity to better understand the role of these noncoding RNAs on RNA regulation in placental development throughout gestation among the sexes. In addition, we have corresponding banked maternal plasma from pregnancies in which villi are banked. We have recently isolated placental RNA from our stored samples and intend to use these samples to identify key markers of placental function that are reflective of the intrauterine placenta. Thus, we intend to use our established banked first trimester and term placental samples to establish a normative and sexually distinct placental signature of total RNA (noncoding and coding) throughout gestation. We also intend to identify functional activity of noncoding RNAs on placental function followed by the development of a functionally relevant signature that can be identified in the maternal circulation.