Coxsackievirus and Adenovirus Receptor, a Tight Junction Protein, in Peri-Implantation Mouse Embryos

Abstract

To understand the role of Coxsackievirus and adenovirus receptor (CAR), a tight junction (TJ) protein, in peri-implantation embryos, developmental expression of CAR and its role in paracellular permeability were examined in mouse embryos. Splice variants for transmembrane CAR, Car1, Car2, and Car3 mRNA, were expressed from 2-cell, morula, and blastocyst stages onward, respectively, whereas mRNA for soluble CAR was expressed in MII oocytes and 4-cell stage onward. On Western blot, ∼46 kDa CAR proteins were detected in blastocysts. During the 4-cell embryos to morula stage, CAR was gradually concentrated at the contacts between blastomeres. In blastocysts, CAR was expressed at the cell contacts within the inner cell mass as well as in the trophectoderm (TE) where CAR was found together with ZO1 at the apical contacts, suggesting that CAR builds up apical TJs in TE and mediates cell adhesion in TE and inner cell mass. In blastocysts, CAR-blocking antibodies under Ca(2+) switching increased the dextran permeability and decreased the volume of blastocoel and H19 and Cdx2 mRNA, suggesting the pivotal role of CAR in the blastocyst development and paracellular permeability barrier in TE. CAR was expressed in TE of implanting embryos as well as endometrial epithelium, suggesting the involvement of CAR in the interaction between implanting embryos and endometrium. At 5-6 days postcoitum, CAR was expressed together with ZO1 in the primitive endoderm, visceral endoderm, and epiblasts facing the pro-amniotic cavity, suggesting that CAR TJs contribute to the separation of epiblast from the blastocoel and development of the pro-amniotic cavity within epiblasts.

Protective Role of Coxsackie-Adenovirus Receptor in the Pathogenesis of Inflammatory Bowel Diseases

“…The role of CAR in regulating permeability has been suggested in previous studies [ 15 , 32 ]. Tight junctions are major structures for maintaining intestinal barrier and substance permeability [ 33 ].…”

Optimal timing of blastocyst vitrification after trophectoderm biopsy for preimplantation genetic screening

“…Actually, TE biopsy appears to cause the rupture of the TJs between TE cells, which are responsible for paracellular sealing for retaining Na + and water molecules inside the blastocoel [ 15 ]. The TJs between TE cells play a crucial role in intercellular integrity, embryo amino acid turnover [ 15 , 30 ], embryonic growth [ 31 ] and implantation [ 32 ]. The paracellular sealing and sodium pump (Na+/K+-ATPase) facilitates gradually increasing fluid accumulation in the blastocoel [ 16 ], resulting in increased pressure on both the TE and ZP to increase blastocoel size to form an expanded blastocyst.…”

The optimal timing of blastocyst vitrification after trophectoderm biopsy of preimplantation genetic screening

“…Actually, TE biopsy appears to cause the rupture of the TJs between TE cells, which are responsible for paracellular sealing for retaining Na + and water molecules inside the blastocoel [15]. The TJs between TE cells play a crucial role in intercellular integrity, embryo amino acid turnover [15,30], embryonic growth [31] and implantation [32]. The paracellular sealing and sodium pump (Na+/K +-ATPase) facilitates gradually increasing fluid accumulation in the blastocoel [16], resulting in increased pressure on both the TE and ZP to increase blastocoel size to form an expanded blastocyst.…”