Evaluation of Blastomere Biopsy Using a Mouse Model Indicates the Potential High Risk of Neurodegenerative Disorders in the Offspring

Abstract

Preimplantation genetic diagnosis (PGD), used in clinical practice, is offered to couples that may suffer from a monogenetic disorder, chromosome aneuploidy, or X-linked disease. However, blastomere biopsy, as an indispensable manipulation during the PGD procedure has not been assessed for its long term health implications. Using a mouse model, we investigated the effect of blastomere biopsy of in vitro cultured four-cell embryos on preimplantation development efficiency, postnatal growth, and physiological and behavioral activity compared with control, non-biopsied embryos. The mice generated after blastomere biopsy showed weight increase and some memory decline compared with the control group. Further protein expression profiles in adult brains were analyzed by a proteomics approach. A total of 36 proteins were identified with significant differences between the biopsied and control groups, and the alterations in expression of most of these proteins have been associated with neurodegenerative diseases. Furthermore hypomyelination of the nerve fibers was observed in the brains of mice in the biopsied group. This study suggested that the nervous system may be sensitive to blastomere biopsy procedures and indicated an increased relative risk of neurodegenerative disorders in the offspring generated following blastomere biopsy. Thus, more studies should be performed to address the possible adverse effects of blastomere biopsy on the development of offspring, and the overall safety of PGD technology should be more rigorously assessed.

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“…The PGD procedure has a high economic burden on patients and more importantly, the risks to offspring health are still debatable. Evidence from animal study indicates that PGD renders an increased risk of neurodegenerative disorders in offspring following blastomere biopsy [39].…”

Embryo biopsy and development: the known and the unknown

“…Studies to assess epigenetic, behavioral, reproductive and/or metabolic health in the pre-or postnatal life following TB have not been published so far, while few research groups have performed studies to assess BB risk(s) and safety (Yu et al 2009, 2013, Sugawara et al 2012, Yang et al 2012, Zeng et al 2013, Sampino et al 2014, Sato et al 2014, Wu et al 2014. Thus, in the following sections, we will focus our attention on BB, rather than TB.…”

“…To clarify the mechanism behind the impaired behavior and stress response, the brain and adrenal glands (peripheral organs) were selected as target organs. Histological and ultrastructural examination of the brain revealed structural abnormalities in the corpora striatum and hippocampus, such as hypomyelination, axonal swelling, neuronal regression and mitochondrial degeneration (Yu et al 2009, Wu et al 2014. Proteomic analysis of brain tissues from BB mice identified 36 differentially expressed proteins, 17 of which are associated with neurodegenerative diseases, including Alzheimer's and Parkinson's disease (Yu et al 2009).…”

“…In the last decade, a few research groups have investigated whether BB could be associated with an increased risk of neurodevelopmental disorders (Yu et al 2009, Zeng et al 2013, Sampino et al 2014, Wu et al 2014. Behavioral tests showed that mice born following BB had impaired memory and motor coordination, increased anxiety and altered responses to threatening or stress stimuli.…”

“…body weight, blood parameters or gross morphology of major internal organs) (BB: Cui et al 1993Cui et al , 1994TB: Gentry & Critser 1995). However, in the last decade, different research groups have described increased body weight/size and impaired behavior in BB mice and have suggested reduced fertility in adult females (Yu et al 2009, Zeng et al 2013, Sampino et al 2014, Wu et al 2014). …”