title: Intrauterine infusion of latency-associated peptide (LAP) during early porcine pregnancy affects conceptus elongation and placental size.
abstract: In the pig, transforming growth factor beta (TGFB), TGFB receptors (TGFBRs), and integrins are present during the peri-implantation period. Latency-associated peptide (LAP), a part of latent TGFB, can bind to integrin heterodimers via its Arg-Gly-Asp (RGD) sequence; therefore, ligand-receptor interactions between TGFB and TGFBRs, along with LAP and integrin heterodimers, may be functional in mediating events supporting conceptus elongation and attachment. With the use of surgically implantable osmotic pumps, we were able to maintain pregnancy with the aim of mechanistically altering in vivo receptor-ligand interactions involving TGFB with TGFBRs and LAP with integrins during porcine pregnancy. Day 9 pregnant gilts received intrauterine infusions of LAP-RGD, a recombinant mutant of LAP (LAP-RGE), or vehicle control and were ovariohysterectomized on Day 13 or 24 of pregnancy. We hypothesized that intrauterine infusion of LAP-RGD would decrease downstream signaling of TGFB while increasing LAP-integrin interactions and that net effect would enhance conceptus survival and attachment early in the peri-implantation period but possibly increase the chance of abnormal placentation later in pregnancy. Additionally, we hypothesized that infusion of LAP-RGE would disrupt TGFB signals but not alter integrin signaling, and thus the net result would be decreased conceptus survival and abnormal development. Unexpectedly, LAP-RGD intrauterine infusions resulted in a reduction of conceptus elongation, whereas infusions of LAP-RGE permitted implantation and placentation but resulted in larger fetal weight, allantois length, and allantoic fluid volume. Results suggest TGFB and integrins are contributing factors in the regulation of conceptus elongation and placental and fetal size.
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA.
authors.forename: Dana A
authors.initials: DA
authors.lastname: Massuto
authors.forename: R Neil
authors.initials: RN
authors.lastname: Hooper
authors.forename: Eric C
authors.initials: EC
authors.lastname: Kneese
authors.forename: Greg A
authors.initials: GA
authors.lastname: Johnson
authors.forename: Nancy H
authors.initials: NH
authors.lastname: Ing
authors.forename: Bradley R
authors.initials: BR
authors.lastname: Weeks
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Jaeger
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects*; D004333:Drug Administration Routes; D010064:Embryo Implantation / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D020567:Fetal Weight / Q000187:drug effects; D005865:Gestational Age; D007260:Infusion Pumps / Q000662:veterinary; D009929:Organ Size; D009995:Osmosis; D010920:Placenta / Q000166:cytology / Q000187:drug effects*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects; D013552:Swine; D053773:Transforming Growth Factor beta1 / Q000008:administration & dosage* / Q000494:pharmacology; D014599:Uterus
chemical_list: D053773:Transforming Growth Factor beta1