title: p38 MAPK regulates cavitation and tight junction function in the mouse blastocyst.
abstract: Blastocyst formation is essential for implantation and maintenance of pregnancy and is dependent on the expression and coordinated function of a series of proteins involved in establishing and maintaining the trans-trophectoderm ion gradient that enables blastocyst expansion. These consist of Na/K-ATPase, adherens junctions, tight junctions (TJ) and aquaporins (AQP). While their role in supporting blastocyst formation is established, the intracellular signaling pathways that coordinate their function is unclear. The p38 MAPK pathway plays a role in regulating these proteins in other cell types and is required for embryo development at the 8-16 cell stage, but its role has not been investigated in the blastocyst.
  
  
  OBJECTIVE
  p38 MAPK regulates blastocyst formation by regulating blastocyst formation gene expression and function.
  
  
  METHODS
  Embryos were cultured from the early blastocyst stage for 12 h or 24 h in the presence of a potent and specific p38 MAPK inhibitor, SB 220025. Blastocyst expansion, hatching, gene family expression and localization, TJ function and apoptosis levels were analyzed.
  
  
  RESULTS
  Inhibition of the p38 MAPK pathway reduced blastocyst expansion and hatching, increased tight junction permeability, affected TJP1 localization, reduced Aqp3 expression, and induced a significant increase in apoptosis.
  
  
  CONCLUSIONS
  The p38 MAPK pathway coordinates the overall events that regulate blastocyst formation.
authors.affiliation: Department of Obstetrics and Gynaecology, The University of Western Ontario, London, Ontario, Canada. cejbell@gmail.com
authors.forename: Christine E
authors.initials: CE
authors.lastname: Bell
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Watson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051400:Aquaporin 3 / Q000235:genetics / Q000378:metabolism; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D010539:Permeability / Q000187:drug effects; D011247:Pregnancy; D021381:Protein Transport / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D019108:Tight Junctions / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D011743:Pyrimidines; D012333:RNA, Messenger; C110631:SB 220025; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D051400:Aquaporin 3; D048051:p38 Mitogen-Activated Protein Kinases