Title Aberrant Epigenetic Modification in Murine Brain Tissues of Offspring from Preimplantation Genetic Diagnosis Blastomere Biopsies
Authors Zhao, Hong-Cui
Zhao, Yue
Li, Min
Yan, Jie
Li, Li
Li, Rong
Liu, Ping
Yu, Yang
Qiao, Jie
Affiliation Peking Univ, Hosp 3, Ctr Reprod Med, Dept Obstet & Gynecol, Beijing 100191, Peoples R China.
Minist Educ, Key Lab Assisted Reprod, Beijing, Peoples R China.
Beijing Key Lab Reprod Endocrinol & Assisted Repr, Beijing, Peoples R China.
Peking Univ, Hosp 3, Dept Obstet & Gynecol, 49 North Huayuan Rd, Beijing 100191, Peoples R China.
Keywords assisted reproductive technology
behavior
blastocoel formation
blastomere biopsy
compaction
developmental biology
epigenetics
methylation
preimplantation genetic diagnosis
rodents (rats, mice, guinea pigs, voles)
ASSISTED REPRODUCTIVE TECHNOLOGIES
INTRACYTOPLASMIC SPERM INJECTION
IN-VITRO FERTILIZATION
MOUSE EMBRYO
IMPRINTING DEFECTS
DNA METHYLATION
BIRTH-DEFECTS
RISK
EXPRESSION
DISEASE
Issue Date 2013
Publisher 生殖生物学
Citation BIOLOGY OF REPRODUCTION.2013,89,(5).
Abstract Preimplantation genetic diagnosis (PGD) has been prevalent in the field of assisted reproductive technology, yet the long-term risks of PGD to offspring remain unknown. In the present study, the early development of PGD embryos, postimplantation characteristics, and birth rate following PGD were determined. Moreover, the behavior of the offspring conceived from the biopsied embryos was evaluated with the Morris water maze and pole climbing tests. Finally, the epigenetic modification of the global genome and methylation patterns for the H19, Igf2, and Snrpn imprinted genes were identified. The results indicated a significant delay in the blastocoel formation of PGD embryos and a decrease in the implantation ability of these embryos, which was related to the decreased number of cells in the PGD blastocysts. The PGD mice spent more time on both the nontrained quadrant of the water maze and climbing down the pole. Furthermore, the 5-hydroxymethylcytosine content in the brain tissues of PGD mice was significantly increased, but no difference was found in 5-methylcytosine content. The differentially methylated regions of H19/Igf2 exhibited decreased methylation patterns, but that of Snrpn was normal, compared to the control group. Quantitative RT-PCR indicated that Igf2 mRNA expression was significantly decreased but that H19 and Snrpn mRNAs were expressed normally. In conclusion, blastomere biopsies in PGD procedures carry potential risks to embryo development and the behavior of resulting offspring; these risks may arise from aberrant epigenetic modification and methylation patterns in brain tissues. Further studies are needed to better understand the risks associated with PGD.
URI http://hdl.handle.net/20.500.11897/309237
ISSN 0006-3363
DOI 10.1095/biolreprod.113.109926
Indexed SCI(E)
PubMed
Appears in Collections: 第三医院

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