title: Transforming growth factor beta (TGFB) signaling is activated during porcine implantation: proposed role for latency-associated peptide interactions with integrins at the conceptus-maternal interface.
abstract: The process of implantation is mediated by a complex network of signaling and adhesive factors. In the pig, latent and active transforming growth factor beta (TGFB), TGFB receptors (TGFBR), and integrins (ITGs) are present during the peri-implantation period. TGFB signals via TGFBR and activates downstream effector SMAD proteins 2 and 3 (p-SMAD2/3). Latency-associated peptide (LAP), part of the latent TGFB complex, is known to bind to ITG heterodimers and activate TGFB. We hypothesize that active TGFBs and TGFBRs along with LAP and ITGs functionally interact at the conceptus-maternal interface to mediate events essential for conceptus development and attachment in pigs. Uteri and conceptuses from days 10, 12, 16, 20, and 24 pregnant gilts were immunostained for TGFB, LAP, and ITG subunits (ITGAV, ITGB1, ITGB3, ITGB5, ITGB6, and ITGB8). Activation of TGFBRs was evaluated by the presence of phosphorylated downstream effector SMAD2/3. Binding of LAP to ITGs was also evaluated using porcine trophectoderm cells. Abundant active TGFB was detected at the apical surfaces of epithelia at the conceptus-maternal interface, and p-SMAD2/3 was detected at both conceptus attachment and nonattachment sites during implantation. Separate aggregates of LAP, ITGB1, ITGB5, and later ITGB3 were detected at the porcine conceptus-maternal interface, and binding of LAP to ITGs on apical surfaces was demonstrated. Results suggest that functional LAP-ITG adhesion complexes support conceptus attachment and promote TGFB activation leading to TGFB interaction with TGFBR supporting events of porcine implantation.
authors.affiliation: Departments of Veterinary Integrative Biosciences Veterinary Large Animal Clinical Sciences Animal Science, Texas A&M University, College Station, Texas 77843-4458, USA.
authors.forename: Dana A
authors.initials: DA
authors.lastname: Massuto
authors.forename: Eric C
authors.initials: EC
authors.lastname: Kneese
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Johnson
authors.forename: Robert C
authors.initials: RC
authors.lastname: Burghardt
authors.forename: R Neil
authors.initials: RN
authors.lastname: Hooper
authors.forename: Nancy H
authors.initials: NH
authors.lastname: Ing
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Jaeger
mesh_terms: D000818:Animals; D019921:Biotinylation; D002460:Cell Line; D010064:Embryo Implantation; D005260:Female; D005865:Gestational Age; D007150:Immunohistochemistry; D039641:Integrin beta Chains / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D039661:Integrin beta3 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D010766:Phosphorylation; D011247:Pregnancy; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D013552:Swine; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism; D014599:Uterus / Q000378:metabolism*
chemical_list: D039641:Integrin beta Chains; D019012:Integrin beta1; D039661:Integrin beta3; D016023:Integrins; D010455:Peptides; D011498:Protein Precursors; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; C084344:integrin beta5; C472416:latency-associated propeptide, TGF-beta