Hum. Reprod. Advance Access published online on July 10, 2007
Human Reproduction, doi:10.1093/humrep/dem147
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Human embryos developing in vitro are susceptible to impaired epithelial junction biogenesis correlating with abnormal metabolic activity
1 School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK 2 Department of Biology, University of York, PO Box 373, York YO10 5YW, UK 3 Assisted Conception Unit, Clarendon Wing, Leeds General Infirmary, Leeds LS1 9NS, UK 4 Reproduction and Early Development Research Group, Leeds Institute of Genetics, Health and Therapeutics, D Floor, Clarendon Wing, Leeds General Infirmary, Belmont Grove, Leeds LS2 9NS, UK 5 Developmental Origins of Health and Disease Division, School of Medicine, University of Southampton, Princess Anne Hospital, Southampton SO16 5YA, UK
8 Correspondence address. Developmental Origins of Health and Disease Division, Institute of Developmental Sciences, D08/MP887 Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. Tel./Fax: +44 2380594401; E-mail: jje{at}soton.ac.uk
BACKGROUND: Blastocyst biogenesis occurs over several cell cycles during the preimplantation period comprising the gradual expression and membrane assembly of junctional protein complexes which distinguish the outer epithelial trophectoderm (TE) cells from the inner cell mass (ICM). In the human, TE integrity and the formation of a junctional seal can often be impaired. Embryos likely to result in a successful pregnancy after transfer are mostly selected according to morphological criteria. Recent data suggest that non-invasive measurement of amino acid turnover may be useful to complement such morphological scores. Whether morphological and metabolic criteria can be linked to poor TE differentiation thereby underpinning developmental predictions mechanistically remains unknown.
METHODS: We examined TE intercellular junction formation in human embryos by immunofluorescence and confocal microscopy and correlated this process with morphological criteria and amino acid turnover during late cleavage.
RESULTS: Our results show that TE differentiation may be compromised by failure of membrane assembly of specific junction constituents. This abnormality relates more closely to metabolic profiles than morphological criteria.
CONCLUSION: Our data identify that amino acid turnover can predict TE differentiation. These findings are the first to link two mechanisms, metabolism and junction membrane assembly, which contribute to early embryo development.
Key words: human embryo/trophectoderm/blastocyst/tight junction/amino acid metabolism
6 Present address: Developmental Origins of Health and Disease Division, School of Medicine, University of Southampton, Princess Anne Hospital, Southampton SO16 5YA, UK
7 Present address: Centre for Human Development, Stem Cells and Regeneration, Division of Human Genetics, University of Southampton, Duthie Building (MP808), Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
The first two authors contributed equally to this study.
Submitted on January 9, 2007; resubmitted on March 9, 2007; accepted on May 2, 2007.