Effect of ICSI on gene expression and development of mouse preimplantation embryos

Department of Obstetric, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Human Reproduction (Impact Factor: 4.57). 10/2010; 25(12):3012-24. DOI: 10.1093/humrep/deq266
Source: PubMed


In vitro culture (IVC) and IVF of preimplantation mouse embryos are associated with changes in gene expression. It is however not known whether ICSI has additional effects on the transcriptome of mouse blastocysts.
We compared gene expression and development of mouse blastocysts produced by ICSI and cultured in Whitten's medium (ICSI(WM)) or KSOM medium with amino acids (ICSI(KSOMaa)) with control blastocysts flushed out of the uterus on post coital Day 3.5 (in vivo). In addition, we compared gene expression in embryos generated by IVF or ICSI using WM. Global pattern of gene expression was assessed using the Affymetrix 430 2.0 chip.
Blastocysts from ICSI fertilization have a reduction in the number of trophoblastic and inner cell mass cells compared with embryos generated in vivo. Approximately 1000 genes are differentially expressed between ICSI blastocyst and in vivo blastocysts; proliferation, apoptosis and morphogenetic pathways are the most common pathways altered after IVC. Unexpectedly, expression of only 41 genes was significantly different between embryo cultured in suboptimal conditions (WM) or optimal conditions (KSOM(aa)).
Our results suggest that fertilization by ICSI may play a more important role in shaping the transcriptome of the developing mouse embryo than the culture media used.

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    • "For example, Hewitson et al. (2002) showed that ICSI was associated with altered sperm chromatin decondensation, retention of the perinuclear theca, and altered pronuclear formation, all of which may affect cell cycle dynamics and epigenetic remodeling of the male pronucleus. Furthermore, in animal and human studies ICSI is associated with altered early embryonic transcription and decreased number of cells in the inner cell mass (Giritharan et al., 2010). "

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    • "Last but not least, a dramatic change in gene expression has been reported in ICSI as compared to the in vivo situation in the mouse. Mostly, genes related to cell function and development were found to be up- or down regulated (4). "
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    • "The causes of the observed effects apparently included both the DNA fragmentation of the sperm and the ICSI procedure itself [95]. Giritharan et al. [96] also reported gene expression changes at the blastocyst stage induced by ICSI treatment in a different mouse, i.e. CF1 × C57BL/6. "
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