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Publication : The Cxadr-Adam10 complex plays pivotal roles in tight junction integrity and early trophoblast development in mice.

First Author  Jeong Y Year  2019
Journal  Mol Reprod Dev Volume  86
Issue  11 Pages  1628-1638
PubMed ID  31373105 Mgi Jnum  J:294136
Mgi Id  MGI:6454779 Doi  10.1002/mrd.23250
Citation  Jeong Y, et al. (2019) The Cxadr-Adam10 complex plays pivotal roles in tight junction integrity and early trophoblast development in mice. Mol Reprod Dev 86(11):1628-1638
abstractText  Understanding preimplantation embryo development has important implications for assisted reproductive technologies (ARTs) after the introduction of in vitro fertilisation and embryo transfer because most embryonic losses occur during pre/peri-implantation. Recent studies have shown that tight junctions (TJs) are important components for embryos to develop to the blastocyst stage. However, their biological function after cavitation has not been extensively studied. We examined TJ assembly focusing on coxsackievirus and adenovirus receptor (Cxadr) and A disintegrin and metalloproteinase 10 (Adam10) using siRNA and/or an Adam10-specific inhibitor (GI254023X). TJ-associated genes, including occludin and tight junction protein 1 (Tjp1), were downregulated in the Cxadr knockdown (KD) embryos but were unaltered in Adam10 KD embryos. However, Adam10 KD or chemical inhibition affected subcellular localisation of Adam10, Cxadr, and Tjp1, leading to disrupted TJ assembly. Furthermore, Cxadr KD or GI254023X-treated blastocysts showed a relatively smaller outgrowth area and aberrant expression of transcription factor AP-2gamma, a trophoblast-specific marker in the in vitro embryo outgrowth assay. In summary, we demonstrated that the Cxadr-Adam10 complex might moderate TJ integrity/stability and play pivotal roles during early embryonic development. Collectively, understanding the establishment of the TJ complex and its integrity will provide insight into translational research for predicting and selecting developmental competency for ART.
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