PMID- 31373105 OWN - NLM STAT- MEDLINE DCOM- 20200707 LR - 20200707 IS - 1098-2795 (Electronic) IS - 1040-452X (Linking) VI - 86 IP - 11 DP - 2019 Nov TI - The Cxadr-Adam10 complex plays pivotal roles in tight junction integrity and early trophoblast development in mice. PG - 1628-1638 LID - 10.1002/mrd.23250 [doi] AB - 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. CI - (c) 2019 Wiley Periodicals, Inc. FAU - Jeong, Yelin AU - Jeong Y AD - Division of Animal and Dairy Sciences, College of Agriculture and Life Sciences, Chungnam National University, Daejeon, Republic of Korea. AD - Disease Model Research Laboratory, Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea. FAU - Ock, Sun-A AU - Ock SA AD - National Institute of Animal Science, Rural Development Administration, Jeollabuk-do, Republic of Korea. FAU - Yoo, Jae Gyu AU - Yoo JG AD - National Institute of Animal Science, Rural Development Administration, Jeollabuk-do, Republic of Korea. FAU - Yu, Dae-Yeul AU - Yu DY AD - Disease Model Research Laboratory, Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea. AD - Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea. FAU - Choi, Inchul AU - Choi I AUID- ORCID: 0000-0001-5011-2658 AD - Division of Animal and Dairy Sciences, College of Agriculture and Life Sciences, Chungnam National University, Daejeon, Republic of Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190802 PL - United States TA - Mol Reprod Dev JT - Molecular reproduction and development JID - 8903333 RN - 0 (CLMP protein, mouse) RN - 0 (Coxsackie and Adenovirus Receptor-Like Membrane Protein) RN - 0 (Membrane Proteins) RN - 0 (Multiprotein Complexes) RN - 0 (RNA, Small Interfering) RN - 0 (Tjp1 protein, mouse) RN - 0 (Transcription Factor AP-2) RN - 0 (Zonula Occludens-1 Protein) RN - EC 3.4.- (Amyloid Precursor Protein Secretases) RN - EC 3.4.24.81 (ADAM10 Protein) RN - EC 3.4.24.81 (Adam10 protein, mouse) SB - IM MH - ADAM10 Protein/genetics/*metabolism MH - Amyloid Precursor Protein Secretases/genetics/*metabolism MH - Animals MH - Coxsackie and Adenovirus Receptor-Like Membrane Protein/genetics/*metabolism MH - Down-Regulation MH - Membrane Proteins/genetics/*metabolism MH - Mice MH - Multiprotein Complexes/genetics/*metabolism MH - RNA, Small Interfering/genetics MH - Tight Junctions/genetics/*metabolism MH - Transcription Factor AP-2/genetics/metabolism MH - Trophoblasts/cytology/*metabolism MH - Zonula Occludens-1 Protein/biosynthesis/genetics OTO - NOTNLM OT - Adam10 OT - Cxadr OT - blastocyst OT - embryo transfer OT - tight junction EDAT- 2019/08/03 06:00 MHDA- 2020/07/08 06:00 CRDT- 2019/08/03 06:00 PHST- 2018/12/10 00:00 [received] PHST- 2019/07/16 00:00 [accepted] PHST- 2019/08/03 06:00 [pubmed] PHST- 2020/07/08 06:00 [medline] PHST- 2019/08/03 06:00 [entrez] AID - 10.1002/mrd.23250 [doi] PST - ppublish SO - Mol Reprod Dev. 2019 Nov;86(11):1628-1638. doi: 10.1002/mrd.23250. Epub 2019 Aug 2.