Noncoding RNA regulation of the human placental transcriptome among the sexes

摘要 胎盘对胎儿的健康和发育至关重要，也是产妇健康的潜在标志， 明白传统上，人类胎盘功能的研究集中在足月时获得的样本， 限制了我们理解整个人类正常胎盘发育和功能的能力， 怀孕在整个怀孕期间出现的状况和疾病的发展归因于 胎盘发育和随后的功能最可能发生在妊娠早期。早期直接胎盘 评估可以通过在早期妊娠晚期进行的绒毛膜绒毛取样（CVS）来实现。 这些绒毛用于细胞遗传学检测，也是了解胎盘发育的独特窗口。我们 开发了将未使用的绒毛储存起来用于随后的多组学测试包括基因组学的技术， 表观基因组学和转录组学，并从这些妊娠中收集足月胎盘样本， 了解整个妊娠期胎盘发育和潜在功能的窗口。最近，我们发现 妊娠早期常染色体和性染色体上表达的一些基因的差异 胎盘，与足月时鉴定的胎盘不同，表明胎盘发育存在性别差异 早在怀孕的头三个月此外，我们还确定了非编码RNA组分的差异， 性别，由常染色体和性染色体表达。由于这些非编码RNA很重要， 转录活性的调节因子，因此整体功能，他们可以解释更微妙的性别 在胎儿发育和疾病中观察到的差异是胎盘发育的结果。然而，性 通过非编码RNA进行基因调控的二态性在正常胎盘中尚未研究过。 发展因此，利用我们已经储存的样本和我们的基因组学生物信息学专业知识，我们 有机会更好地了解这些非编码RNA对胎盘中RNA调节的作用， 两性在整个妊娠期的发育。此外，我们有相应的银行产妇 怀孕时绒毛堆积的血浆。我们最近从我们储存的胎盘RNA中分离出了 样本，并打算使用这些样本来确定反映胎盘功能的关键标志物， 子宫内胎盘因此，我们打算使用我们建立的前三个月和术语胎盘 样本，以建立总RNA（非编码和编码）的规范性和性别不同的胎盘特征 整个妊娠期。我们还打算鉴定非编码RNA对胎盘功能的功能活性 随后是可以在母体循环中识别的功能相关签名的开发。

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.