Abnormal Development at Early Postimplantation Stage in Mouse Embryos After Preimplantation Genetic Diagnosis

Preimplantation genetic diagnosis (PGD) is an established procedure for the genetic analysis of embryos. To assess the effect of the procedure on early embryonic development, we generated a murine experimental system, including mice implanted with biopsied in vitro cultured embryos, control mice implanted with in vitro cultured embryos without biopsy, and mice with naturally conceived embryos. Embryos at the 7.5‐dpc stage were isolated from all three groups and the embryo implantation rate, the survival rate of implanted embryos, and the developmental stage of surviving embryos were carefully assessed and compared among all three groups. We found the implantation rate was similar between biopsied and control group embryos (67.92% vs. 66.67%). However, the survival rate of implanted embryos in the biopsied group (49.31%) was significantly lower than that of the control (60.91%) and normal groups (96.24%) at 7.5 dpc. In addition, the survival rate of control group embryos was significant lower than that of normal group embryos. Classification of the precise developmental stages of randomly selected live implanted embryos at 7.5 dpc revealed no differences among the three groups. Our results indicate that blastomere biopsy does not adversely affect embryo implantation. The PGD procedure, in particular blastomere biopsy, increases the rate of embryo death at 4.5–7.5 dpc, but does not affect the development of surviving 7.5 dpc embryos. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.

[1]  J. Fisher,et al.  Looking downstream: a review of the literature on physical and psychosocial health outcomes in adolescents and young adults who were conceived by ART. , 2011, Human reproduction.

[2]  Michael Weber,et al.  Targets and dynamics of promoter DNA methylation during early mouse development , 2010, Nature Genetics.

[3]  E. Maltepe,et al.  Effect of the method of conception and embryo transfer procedure on mid-gestation placenta and fetal development in an IVF mouse model. , 2010, Human reproduction.

[4]  J. Simpson.  Preimplantation genetic diagnosis at 20 years , 2010, Prenatal diagnosis.

[5]  P. Haentjens,et al.  Report on a consecutive series of 581 children born after blastomere biopsy for preimplantation genetic diagnosis. , 2010, Human reproduction.

[6]  M. Roelants,et al.  Growth and health outcome of 102 2-year-old children conceived after preimplantation genetic diagnosis or screening. , 2009, Early human development.

[7]  Yang Yu,et al.  Evaluation of Blastomere Biopsy Using a Mouse Model Indicates the Potential High Risk of Neurodegenerative Disorders in the Offspring* , 2009, Molecular & Cellular Proteomics.

[8]  D. Amor,et al.  A review of known imprinting syndromes and their association with assisted reproduction technologies. , 2008, Human reproduction.

[9]  D. Hu,et al.  Gender determination and detection of aneuploidy in single cells using DNA array-based comparative genomic hybridization. , 2007, Methods in molecular medicine.

[10]  J. Beyene,et al.  Perinatal Outcomes of Singleton Pregnancies Achieved by In Vitro Fertilization: A Systematic Review and Meta-Analysis , 2005 .

[11]  L. Gianaroli,et al.  Over a decade of experience with preimplantation genetic diagnosis: a multicenter report. , 2004, Fertility and sterility.

[12]  L. Schieve,et al.  Perinatal Outcome Among Singleton Infants Conceived Through Assisted Reproductive Technology in the United States , 2004, Obstetrics and gynecology.

[13]  D. Hu,et al.  Aneuploidy detection in single cells using DNA array-based comparative genomic hybridization. , 2004, Molecular human reproduction.

[14]  Yvonne W Wu,et al.  Perinatal Outcomes in Singletons Following In Vitro Fertilization: A Meta-Analysis , 2004, Obstetrics and gynecology.

[15]  Pgd,et al.  Preimplantation genetic diagnosis. , 2019, Fertility and sterility.

[16]  Antoine Flahault,et al.  In vitro fertilization may increase the risk of Beckwith-Wiedemann syndrome related to the abnormal imprinting of the KCN1OT gene. , 2003, American journal of human genetics.

[17]  B. Levy,et al.  Cytogenetics in reproductive medicine: the contribution of comparative genomic hybridization (CGH). , 2003, BioEssays : news and reviews in molecular, cellular and developmental biology.

[18]  W. Reik,et al.  Beckwith-Wiedemann syndrome and assisted reproduction technology (ART) , 2003, Journal of medical genetics.

[19]  Andrew P Feinberg,et al.  Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19. , 2003, American journal of human genetics.

[20]  Kate Hardy,et al.  Are we ignoring potential dangers of in vitro fertilization and related treatments , 2002 .

[21]  K. Hardy,et al.  Are we ignoring potential dangers of in vitro fertilization and related treatments? , 2002, Nature cell biology.

[22]  L. Wilton.  Preimplantation genetic diagnosis for aneuploidy screening in early human embryos: a review , 2002, Prenatal diagnosis.

[23]  Wendy Dean,et al.  Dynamic reprogramming of DNA methylation in the early mouse embryo. , 2002, Developmental biology.

[24]  T. D’Hooghe,et al.  Superovulation of female mice delays embryonic and fetal development. , 2001, Human reproduction.

[25]  G. Ertzeid,et al.  The impact of ovarian stimulation on implantation and fetal development in mice. , 2001, Human reproduction.

[26]  G. Ertzeid,et al.  P-146. The impact of ovarian hyperstimulation on implantation and fetal development in mice , 1999 .

[27]  T. Davies,et al.  Staging of gastrulating mouse embryos by morphological landmarks in the dissecting microscope. , 1993, Development.

[28]  A. H. Handyside,et al.  Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification , 1990, Nature.