, Volume 15, Issue 4, pp 359-365

Empreinte parentale et Aide Médicale à la Procréation (AMP)

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Résumé

La prise en charge de l’infertilité a débuté il y a plus de deux siècles par la réalisation d’inséminations artificielles, technique interférant peu sur le processus de reproduction puisque la fécondation se déroulein vivo. Les années 80 ont vu l’émergence de la fécondationin vitro (FIV) nécessitant une stimulation hormonale soutenue, une fécondation exvivo et une culture embryonnaire. Enfin, l’arrivée de l’ICSI (Intra Cytoplasmic Sperm Injection) a révolutionné la prise en charge des couples en permettant de créer un embryon par simple microinjection d’un spermatozoïde, même anormal ou immature, dans un ovocyte. Rapidement, la question de l’impact de ces techniques sur la santé des enfants ainsi conçus a été posée. Des études récentes ont suggéré un lien entre aide médicale à la procréation et développement de pathologies d’empreinte. En effet, l’empreinte parentale établie spécifiquement sur chacun des gamètes et transmise à l’embryon peut être sensible à des facteurs externes. La manipulation et la culturein vitro des gamètes et embryons, inhérentes à la réalisation de la FIV/ICSI, pourraient avoir des conséquences sur l’établissement et/ou la conservation de l’empreinte. La connaissance des mécanismes d’acquisition et de maintien de l’empreinte et l’analyse de leur dérégulation sont nécessaires pour évaluer ce risque potentiel.

Abstract

Medical intervention in procreation is not recent, as the first artificial insemination (AI) was performed more than two centuries ago. However, the interference in the reproductive process with Al is limited. The first major change concerned the possibility of fertilizing oocytesin vitro (IVF) and culture of preimplantation embryos before their transfer to the uterus. In the early nineties, it was shown that direct injection of a single spermatozoon, even abnormal or immature, into an oocyte could result in a viable embryo and child. These techniques expanded very rapidly and 45,000 IVFs, with ICSI in 50% of cases, were performed in France in 2001 (FIVNAT). Although a high incidence of major defects has not been reported, the health status of children born by these techniques is a growing concern. Congenital malformations [Hansenet al., 2002], chromosomal abnormalities [Van Steirteghemet al., 2002], neurological disorders [Stromberget al., 2002] and low birth weight [Schieveet al., 2002] have been observed and discussed, but none of them seems to be statistically much more frequent after assisted reproductive technology (ART). It is important to determine the mechanism of these defects in order to prevent them. These risks may be related to the parents’ health status and to their infertility, but they could also be linked to the techniques used for procreation. Recently, several human and animal studies have suggested an increased risk of imprinting disorders in ART offspring [Debaunet al., 2003; Gicquelet al., 2003; Maheret al., 2003; Hallidayet al., 2004]. Several elements can be considered to be responsible for these defects and each step of reproductive technology could be concerned and must be studied. Priority should be given to confirm the incidence of rare genomic imprinting diseases, such as Beckwith Wiedemann Syndrome and Angelman Syndrome after ART. Should systematic analysis of the methylation status of several imprinted genes therefore be performed to evaluate the respective influence of the use of immature gametes, ovarian stimulation and embryo culture involved in IVF/ICSI?

It would also be important to evaluate other epigenetic modifications to determine the role of epigenetic deregulations that could be related to ART.

Prix du meilleur DESS (Biologie de la Reproduction) SALF 2004