Expression of 11 members of the BCL-2 family of apoptosis regulatory molecules during human preimplantation embryo development and fragmentation
Abstract
Apoptosis during preimplantation development has received much interest because of its potential role in eliminating defective cells. Although development in humans is characterised by a high degree of genetic abnormality, little is known of the regulation of apoptosis in embryos. By PolyA PCR we analysed expression of 11 BCL-2 genes in individual human embryos representative of normal development and in severely fragmented embryos. We demonstrate constitutive expression of BAX in virtually all embryos at all stages of development, and variable expression of BCL2, BCL-XL, BCL-W, MCL-1 BAK, BAD, BOKL, BID, BIK, and BCL-XS. The frequency of expression of pro- and anti-apoptotic BCL-2 members was similar throughout development, except at the two-cell stage where pro-apoptotic genes predominated. Protein expression was confirmed for BCL-2, MCL-1, BCL-X, BAX, BAD, and activated caspase 3. BCL-2 protein was associated with mitochondria but expressed inconsistently in the blastocyst inner cell mass. Consistent differences between morphologically intact and fragmented embryos included the expression of BAK in fragmented but not intact four-cell embryos. Our study addresses the importance of examining single human embryos representative of the viable population for a large number of genes, in order to establish meaningful expression profiles and provide information on overlapping function in a large gene family.
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Aβ42-mediated upregulation occurred in expression of genes encoding cytokines IL-1β, CEX-1, TNF-α, COX-2, B94, and proapoptotic Bax and Bik proteins.
“These analyses indicated significant Aβ42-mediated upregulation in the expression of a family of genes encoding the cytokines IL-1β, CEX-1, and TNF-α, COX-2, B94, and the proapoptotic Bax and Bik proteins (Guo et al., 1998; Metcalfe et al., 2004; Tarte et al., 2004).”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Metcalfe et al., 2004
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- Authors
- Metcalfe, A. D., Hunter, H. R., Bloor, D. J., Lieberman, B. A., Picton, H. M., Leese, H. J., Kimber, S. J., & Brison, D. R.
- Affiliations
- University of Manchester (GB)
- St Mary's Hospital (GB)
- Leeds General Infirmary (GB)
- University of York (GB)
- Corresponding author
- Brison, Daniel R.
- Venue
- Molecular Reproduction and Development
- Publisher
- Wiley
- Published
- 2004-03-18
- Volume
- 68
- Issue
- 1
- Pages
- 35-50
- ISSN
- 1040-452X (ISSN-L)
- 1098-2795
- OpenAlex
- W2097317908
- Cited by
- 104
- References
- 75
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 5 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 6 · 2016: 6 · 2015: 1 · 2014: 5 · 2013: 6 · 2012: 3
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Reproduction and Development (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- University of Brighton Repository (University of Brighton) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Bcl-2 family proteins, apoptosis, preimplantation embryo development, embryo fragmentation, Bax, Bcl-xL, Mcl-1, Bad, Bak, Bcl-x, Bcl-w, Bid, BIK, caspase-3, mitochondrial protein expression, inner cell mass, gene expression profiling
- MeSH terms
- Blastocyst, Female, Humans, Microscopy, Fluorescence, Pregnancy, Apoptosis, DNA, Complementary, Gene Expression Regulation, Developmental, Microscopy, Confocal, Proto-Oncogene Proteins c-bcl-2, Gene Expression Profiling, Embryonic Development
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