Genomic Imprinting and Assisted Reproductive Technologies (EPIGEN)
Genomic imprinting, referring to an epigenetic marking resulting in monoallelic gene expression, plays a critical role in development. Recently, various imprinting diseases were reported in animals (Large Offspring syndrome (LOS)) and humans (Beckwith-Wiedemann syndrome (BWS) and Angelman syndrome (AS)) born after ART. In all cases, an imprinting defect was involved (loss of methylation at ICR2 in BWS, at SNRPN in AS and at IGF2R DMR2 in LOS). These data suggest that ART procedures may impair the establishment or the maintenance (following fertilization) of methylation marks at maternally imprinted loci. In view of these data, the aim of this study is to determine if children born following ART exhibit an increased risk of imprinting defects. If the answer is yes, the second objective is to identify the problematic step in the ART procedure and thus to suppress or modify this step.
|Study Design:||Time Perspective: Prospective|
|Official Title:||Assessment of the Risk of Imprinting Defects in Children Born Following Assisted Reproductive Technologies (ART)|
- Assessment of the methylation status at 9 imprinted loci in cord blood collected just after birth. [ Time Frame: At the birth ] [ Designated as safety issue: No ]
- Assessment of other epigenetic marks (histone modifications) at imprinted loci and at non imprinted but epigenetically regulated loci. [ Time Frame: At the birth ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples With DNA
whole blood (serum, ADN) and placenta samples
|Study Start Date:||February 2007|
|Estimated Study Completion Date:||May 2015|
|Estimated Primary Completion Date:||April 2015 (Final data collection date for primary outcome measure)|
Pregnancy after ICSI or IVF
Pregnancy after ovarian stimulation
Methodology: assessment of the methylation status at 9 different imprinted loci (using Southern blot and methyl-specific quantitative PCR) in 3 groups of patients: 150 children naturally conceived, 150 children conceived after ovarian stimulation but with in vivo fertilization, and 150 children conceived after ovarian stimulation and in VITRO fertilization. These analyses will be performed on cord blood. Fragments of placental tissue will also be collected for further analyses. Patients will be selected in maternity hospitals associated with ART departments ( ANTOINE BECLERE HOSPITAL, Cochin HOSPITAL, Saint-Vincent de Paul HOSPITAL, Jean VERDIER HOSPITAL, Tenon HOSPITAL and Dijon Hospital).
This work is also a unique opportunity to establish a DNA, RNA and tissue collection allowing further investigation regarding other epigenetic modifications than DNA methylation, not only at imprinted loci, but also in other genomic regions regulated by epigenetic modifications.
|Contact: Yves LE BOUC, Professor||+33(0) 1 44 73 64 firstname.lastname@example.org|
|Paris, France, 75012|
|Contact: Yves Le Bouc, Professor email@example.com|
|Contact: Sylvie Rossignol, PhD, MD firstname.lastname@example.org|
|Principal Investigator: Yves Le Bouc, Professor|
|Principal Investigator:||Yves Le BOUC, PUPH||Assistance Publique - Hôpitaux de Paris|