580: A pathway analysis of imprinted genes in developing placentae

Abstract

genes in developing placentae Jennifer King, Kai Wang, Huaiyu Mi, Nicole Bender, Rachel Steward, Sue Ingles, Joseph Ouzounian, Melissa Wilson University of Southern California, Department of Obstetrics and Gynecology, Los Angeles, CA, University of Southern California, Department of Psychiatry and The Behavioral Sciences, Los Angeles, CA, University of Southern California, Department of Preventive Medicine, Los Angeles, CA OBJECTIVE: Genomic imprinting has been demonstrated to be integral to fetal development and placentation. The majority of studies on imprinted gene expression in humans have involved term placentas, while placental imprinting is known to be a dynamic process, which evolves during human pregnancy. For these reasons, the distinct imprinted gene expression profile displayed in the early human placenta remains largely unknown. Our objective was to investigate the pattern of imprinted gene expression across first and early second trimester placental development. STUDY DESIGN: We sequenced complementary cDNA from placental villi obtained at 7, 8, 9, and 15 weeks gestation using massively parallel next-generation sequencing (RNA-seq). We used the PANTHER classification system (http://www.pantherdb.org/about.jsp) to evaluate imprinted gene expression at each gestational age in reference to the human genome. We performed a pathway analysis to determine important processes at each time point that differ from the human genome using the Wilcoxon Rank Sum test. We did not use a Bonferroni correction due to the exploratory nature of the analysis. We report the top 15 pathways for each gestational age. RESULTS: Table includes top 15 pathways for each gestational age, none of which are statistically significant after Bonferroni correction. CONCLUSION: Similarities between global gene expression pathways and imprinted gene pathways speak to the importance of imprinted genes in the developing placenta. Imprinted genes have variable expression in early placental development. The top pathway for gestational ages of 8 and 9 weeks appear remarkably similar. At 15 weeks, the molecular pathways of the imprinted genes are notably different compared to earlier gestational age. These observations may reflect changes in imprinted gene expression that occur with changes in oxygen pressure or may be a result of small sample size. Larger studies are required to differentiate. 581 A pathway analysis of the developing placentome Jennifer King, Kai Wang, Huaiyu Mi, Ian Tilley, Rachel Steward, Sue Ingles, Joseph Ouzounian, Melissa Wilson University of Southern California, Department of Obstetrics and Gynecology, Los Angeles, CA, University of Southern California, Department of Psychiatry and The Behavioral Sciences, Los Angeles, CA, University of Southern California, Department of Preventive Medicine, Los Angeles, CA OBJECTIVE: The creation of a suitable intrauterine environment for fetal development is dependent on the proper functioning of placental chorionic villi. Chorionic villi require well-coordinated expression of several transcription factors, cytokines and their receptors, growth factors, and cell cycle regulators. Disruption of the expression of these regulatory factors may lead to placental growth and development disorders. However, gene expression levels across gestatational age have not been fully delineated. Our objective was to investigate the pattern of global gene expression across first and early second trimester placental development. STUDY DESIGN: In the present investigation, we sequenced complementary cDNA from placenta villi obtained at 7, 8, 9, and 15 weeks gestation, using massively parallel next-generation sequencing (RNAseq). We used the PANTHER classification system (http://www.pantherdb.org/about.jsp) to evaluate global gene expression at each gestational age in reference to the human genome. We performed a pathway analysis to determine important processes at each time point that differ from the human genome using the Wilcoxon Rank Sum test with a Bonferroni correction for multiple comparisons. RESULTS: See Table. CONCLUSION: Pathways involved in protein degradation, and regulation of trophoblast invasion are important at all four gestational ages. However, the relative importance of different pathways diverges after that point among the four gestational ages. The possible clinical significance of the ubiquitin proteasome pathway may be underappreciated to date. Additional analyses with a larger sample size are required to understand how these pathways may play a role in predisposing to diseases of placental etiology, such as preeclampsia or intrauterine growth restriction. Pathway description, ( )over or ( )under represented vs human genome (reference) Poster Session IV Academic Issues, Antepartum Fetal, Clinical Ob, Fetus, Genetics, Hypertension, Med-Surg-Diseases, Operative Ob, U/S www.AJOG.org