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Empreinte parentale et Aide Médicale à la Procréation (AMP)

Parental imprinting and Assisted Reproductive Technology (ART)

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.

References

  1. BERGH T., ERICSON A., HILLENSJO T., NYGREN K. G., WENNERHOLM U.B.: Deliveries and children born after invitro fertilisation in Sweden 1982–95: a retrospective cohort study. Lancet, 1999, 354: 1579–1585.

    Article  PubMed  CAS  Google Scholar 

  2. BOERRIGTER P.J., DE BIE J.J., MANNAERTS B.M., VAN LEEUWEN B.P., PASSIER-TIMMERMANS D.P.: Obstetrical and neonatal outcome after controlled ovarian stimulation for IVF using the GnRH antagonist ganirelix. Hum. Reprod., 2002, 17: 2027–2034.

    Article  PubMed  CAS  Google Scholar 

  3. BONDUELLE M., LIEBAERS I., DEKETELAERE V. et al.: Neonatal data on a cohort of 2889 infants born after ICSI (1991–1999) and 2995 infants born after IVF (1983–1999). Hum. Reprod., 2002, 17: 671–694.

    Article  PubMed  Google Scholar 

  4. COX G., BURGER J., LIP V. et al.: Intracytoplasmic sperm injection may increase the risk of imprinting defects. Am. J. Hum. Genet., 2002, 71: 162–164.

    Article  PubMed  CAS  Google Scholar 

  5. DAVIS T.L., YANG G.J., MCCARREY J.R., BARTOLOMEI M.S.: The H19 methylation imprint is erased and re-established differentially on the parental alleles during male germ cell development. Hum. Mol. Genet., 2000, 9: 2885–2894.

    Article  PubMed  CAS  Google Scholar 

  6. DE RYCKE M., LIEBAERS I., VAN STEIRTEGHEM A.: Epigenetic risks related to assisted reproductive technologies: risk analysis and epigenetic inheritance. Hum. Reprod., 2002, 17: 2487–2494.

    Article  PubMed  Google Scholar 

  7. DEBAUN M.R., NIEMITZ E.L., FEINBERG A.P.: Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19. Am. J. Hum. Genet., 2003, 72: 156–160.

    Article  PubMed  CAS  Google Scholar 

  8. DEBAUN M.R., NIEMITZ E.L., MCNEIL D.E. et al.: Epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith-Wiedemann syndrome with cancer and birth defects. Am. J. Hum. Genet., 2002, 70: 604–611.

    Article  PubMed  CAS  Google Scholar 

  9. DOHERTY A.S., MANN M.R., TREMBLAY K.D., BARTOLOMEI M.S., SCHULTZ R.: M. Differential effects of culture on imprinted H19 expression in the preimplantation mouse embryo. Biol. Reprod., 2000, 62: 1526–1535.

    Article  PubMed  CAS  Google Scholar 

  10. EL-MAARRI O., BUITING K., PEERY E.G., et al.: Maternal methylation imprints on human chromosome 15 are established during or after fertilization. Nat. Genet. 2001, 27: 341–344.

    Article  PubMed  CAS  Google Scholar 

  11. GEUNS E., DE RYCKE M., VAN STEIRTEGHEM, A., LIE-BAERS I. Methylation imprints of the imprint control region of the SNRPN-gene in human gametes and preimplantation embryos. Hum. Mol. Genet., 2003, 12: 2873–2879.

    Article  PubMed  CAS  Google Scholar 

  12. GICQUEL C., GASTON V., MANDELBAUM J et al.: In vitro fertilization may increase the risk of Beckwith-Wiedemann syndrome related to the abnormal imprinting of the KCN1OT gene. Am. J. Hum. Genet., 2003, 72: 1338–1341.

    Article  PubMed  CAS  Google Scholar 

  13. HALLIDAY J., OKE K., BREHENY S., ALGAR E., BECKWITH-WIEDEMANN DJ.A.: syndrome and IVF: a case-control study. Am. J. Hum. Genet., 2004, 75: 526–528.

    Article  PubMed  CAS  Google Scholar 

  14. HANSEN M., KURINCZUK J.J., BOWER C., WEBB S.: The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N. Engl. J. Med., 2002, 346: 725–730.

    Article  PubMed  Google Scholar 

  15. HOLM P., WALKER S.K., SEAMARK R.F.: Embryo viability, duration of gestation and birth weight in sheep after transfer of in vitro matured and in vitro fertilized zygotes cultured in vitro or in vivo. J. Reprod. Fertil., 1996, 107: 175–181.

    PubMed  CAS  Google Scholar 

  16. KERJEAN A., COUVERT P., HEAMS T. et al.: In vitro oocyte growth in mice affects maternal primary imprinting establishment. Eur. J. Hum. Genet., 2003, 11: 493–496.

    Article  PubMed  CAS  Google Scholar 

  17. KERJEAN A., DUPONT J.M., VASSEUR C., et al.: Establishment of the paternal methylation imprint of the humanH19 andMEST/PEG1 genes during spermatogenesis. Hum. Mol. Genet., 2000, 9: 2183–2187.

    Article  PubMed  CAS  Google Scholar 

  18. KLEIN G.: Epigenetics: surveillance team against cancer. Nature, 2005, 434: 150.

    Article  PubMed  CAS  Google Scholar 

  19. KOUDSTAAL J., BRUINSE H.W., HELMERHORST F.M. et al.: Obstetric outcome of twin pregnancies after in-vitro fertilization: a matched control study in four Dutch university hospitals. Hum. Reprod., 2000, 15: 935–940.

    Article  PubMed  CAS  Google Scholar 

  20. LUCIFERO D., CHAILLET J.R., TRASLER J.M.: Potential significance of genomic imprinting defects for reproduction and assisted reproductive technology. Hum. Reprod. Update, 2004, 10: 3–18.

    Article  PubMed  CAS  Google Scholar 

  21. LUCIFERO D., MERTINEIT C., CLARKE H.J., BESTOR T.H., TRASLER J.M.: Methylation dynamics of imprinted genes in mouse germ cells. Genomics, 2002, 79: 530–538.

    Article  PubMed  CAS  Google Scholar 

  22. MAHER E.R., AFNAN M., BARRATT C.L.: Epigenetic risks related to assisted reproductive technologies: epigenetics, imprinting, ART and icebergs? Hum. Reprod., 2003, 18: 2508–2511.

    Article  PubMed  Google Scholar 

  23. OBATA Y., KONO T.: Maternal primary imprinting is established at a specific time for each gene throughout oocyte growth. J. Biol. Chem., 2002, 277: 5285–5289.

    Article  PubMed  CAS  Google Scholar 

  24. OLIVENNES F., MANNAERTS B., STRUIJS M., BONDUELLE M., DEVROEY P. Perinatal outcome of pregnancy after GnRH antagonist (ganirelix) treatment during ovarian stimulation for conventional IVF or ICSI: a preliminary report. Hum. Reprod., 2001, 16: 1588–1591.

    Article  PubMed  CAS  Google Scholar 

  25. ORSTAVIK K.H., EILID K., VAN DER HAGEN C.B. et al.: Another case of imprinting defect in a girl with Angelman syndrome who was conceived by intracytoplasmic semen injection. Am. J. Hum. Genet., 2003, 72: 218–219.

    Article  PubMed  CAS  Google Scholar 

  26. SCHIEVE L.A., MEIKLE S.F., FERRE C. et al.: Low and very low birth weight in infants conceived with use of assisted reproductive technology. N. Engl. J. Med., 2002, 346: 731–737.

    Article  PubMed  Google Scholar 

  27. SHI W., HAAF T.: Aberrant methylation patterns at the two-cell stage as an indicator of early developmental failure. Mol. Reprod. Dev., 2002, 63: 329–334.

    Article  PubMed  CAS  Google Scholar 

  28. SINCLAIR K.D., MCEVOY T.G., MAXFIELD E.K. et al.: Aberrant fetal growth and development after in vitro culture of sheep zygotes. J. Reprod. Fertil., 1999, 116: 177–186.

    Article  PubMed  CAS  Google Scholar 

  29. STROMBERG B., DAHLQUIST G., ERICSON A. et al.: Neurological sequelae in children born after in-vitro fertilisation: a population-based study. Lancet, 2002, 359: 461–465.

    Article  PubMed  CAS  Google Scholar 

  30. SUTCLIFFE A.G., D’SOUZA S.W., CADMAN J. et al.: Minor congenital anomalies, major congenital malformations and development in children conceived from cryopreserved embryos. Hum. Reprod., 1995, 10: 3332–3337.

    PubMed  CAS  Google Scholar 

  31. SZABO P.E., MANN J.R.: Biallelic expression of imprinted genes in the mouse germ line: implications for erasure, establishment, and mechanisms of genomic imprinting. Genes Dev., 1995, 9: 1857–1868.

    Article  PubMed  CAS  Google Scholar 

  32. VAN STEIRTEGHEM A., BONDUELLE M., DEVROEY P., LIEBAERS I.: Follow-up of children born after ICSI. Hum. Reprod. Update, 2002, 8: 111–116.

    Article  PubMed  Google Scholar 

  33. WENNERHOLM U.B., BERGH C., HAMBERGER L. et al.: Incidence of congenital malformations in children born after. ICSI. Hum. Reprod., 2000, 15: 944–948.

    Article  CAS  Google Scholar 

  34. YOUNG L.E., FERNANDES K., MCEVOY T.G. et al.: Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nat. Genet., 2001, 27: 153–154.

    Article  PubMed  CAS  Google Scholar 

  35. YOUNG L.E., SINCLAIR K.D., WILMUT I.: Large offspring syndrome in cattle and sheep. Rev. Reprod., 1998, 3: 155–163.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Pierre Jouannet.

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

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Chalas, C., Jouannet, P. Empreinte parentale et Aide Médicale à la Procréation (AMP). Androl. 15, 359–365 (2005). https://doi.org/10.1007/BF03035294

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