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Investigation of epigenetic and morphological placental abnormalities induced by in vitro fertilization

体外受精引起的表观遗传和形态学胎盘异常的研究

基本信息

批准号：
10268155
负责人：
Lisa Anne Vrooman
金额：
$ 2.56万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2020-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10268155
关键词：
Abnormal placentation Address Adverse effects Affect Alleles Animals Assisted Reproductive Technology Biological Assay Cells Child Chorion Complex Cone DNA Methylation Development Disease Elements Embryo Loss Embryo Transfer Epigenetic Process Exhibits Expression Profiling Fellowship Fertilization in Vitro Fluorescent in Situ Hybridization Future Gene Expression Genes Genetic Genetic Transcription Goals Growth and Development function Health Human Iatrogenesis Impairment In Situ Hybridization Individual Infertility Investigation Knockout Mice Laboratories Labyrinth Lasers Locus Control Region Low Birth Weight Infant Mammals Maternal Health Methods Methylation Microdissection Molecular Molecular Analysis Morphology Mus Nutrient Organ Outcome Parents Pathology Pathway interactions Phenotype Physiological Placenta Placentation Play Pregnancy Preparation Procedures Protocols documentation Quantitative Reverse Transcriptase PCR Research Training Risk Role Scientist Superovulation Techniques Testing Tissues Transcript Untranslated RNA Work allantois cell type embryo culture experimental study health of the mother high risk imprint in vitro testing innovation laser capture microdissection mouse model offspring placental morphology single molecule tool transcriptome transcriptome sequencing

项目摘要

Project Abstract Several million babies worldwide have been born via Assisted Reproductive Technologies (ART). Although the majority of ART pregnancies result in healthy babies, ART is associated with a number of adverse effects, including increased risk for low birth weight, abnormal placental development, and rare imprinting disorders. Evidence from animal studies support that ART procedures can induce these effects independent from underlying infertility. Important for proper development and growth, imprinted genes are a unique subset of genes that are monoallelically expressed specific to the parent-of-origin. Notably, imprinted gene expression is regulated by DNA methylation at a discrete element known as the imprinting control region (ICR). Term placentae from mice generated by in vitro fertilization (IVF) display abnormal biallelic expression correlated with ICR hypomethylation for several imprinted genes. Additionally, IVF induces abnormal placental overgrowth. The main objective of this proposal is to test how individual IVF procedures affect placental function and to elucidate the underlying genetic and epigenetic mechanisms of this abnormal placentation. Because the placenta has been shown to be capable of compensating for environmental perturbations, the epigenetic and morphological changes observed may not result in physiological consequences. To address this, formation, cell composition, pathology, and nutrient transport function of the placenta will be assessed in natural, embryo transfer with and without superovulation, embryo culture, and IVF concepti in Aim 1. Because different cell types have distinct epigenetic and expression profiles, several limitations currently exist making molecular analyses of complex tissues, like the placenta, difficult. To remedy this, laser capture microdissection (LCM) and single-molecule quantitative fluorescence in situ hybridization (FISH) will be utilized. To determine gene expression changes that may be responsible for the abnormal placental phenotype, transcriptome analyses will be performed in Aim 2 on ectoplacental cone and chorion (E7.5) and junctional zone and labyrinth (E14.5) isolated by LCM from natural and IVF concepti. In Aim 3, gene expression and single-molecule FISH methods will be employed to test the hypothesis that particular imprinted genes play a role in the underlying mechanism resulting in IVF-induced placental overgrowth. Determining how epigenetic changes influence placentation is important not only in the context of IVF, because the placenta is critical for overall offspring and maternal health. Furthermore, the pipeline developed during this fellowship may prove indispensible for future epigenetic investigations of other complex tissues.

项目摘要