title: System B0,+ amino acid transport regulates the penetration stage of blastocyst implantation with possible long-term developmental consequences through adulthood.
abstract: Amino acid transport system B(0,+) was first characterized in detail in mouse blastocysts over two decades ago. Since then, this system has been shown to be involved in a wide array of developmental processes from blastocyst implantation in the uterus to adult obesity. Leucine uptake through system B(0,+) in blastocysts triggers mammalian target of rapamycin (mTOR) signalling. This signalling pathway selectively regulates development of trophoblast motility and the onset of the penetration stage of blastocyst implantation about 20 h later. Meanwhile, system B(0,+) becomes inactive in blastocysts a few hours before implantation in vivo. System B(0,+) can, however, be activated in preimplantation blastocysts by physical stimuli. The onset of trophoblast motility should provide the physiological physical stimulus activating system B(0,+) in blastocysts in vivo. Activation of system B(0,+) when trophoblast cells begin to penetrate the uterine epithelium would cause it to accumulate its preferred substrates, which include tryptophan, from uterine secretions. A low tryptophan concentration in external secretions next to trophoblast cells inhibits T-cell proliferation and rejection of the conceptus. Suboptimal system B(0,+) regulation of these developmental processes likely influences placentation and subsequent embryo nutrition, birth weight and risk of developing metabolic syndrome and obesity.
authors.affiliation: Department of Biochemistry, Midwestern University, Downers Grove, IL 60515, USA. lvanwi@midwestern.edu.
authors.forename: Lon J
authors.initials: LJ
authors.lastname: Van Winkle
authors.forename: Julia K
authors.initials: JK
authors.lastname: Tesch
authors.forename: Anita
authors.initials: A
authors.lastname: Shah
authors.forename: Allan L
authors.initials: AL
authors.lastname: Campione
mesh_terms: D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000502:physiology*; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D002465:Cell Movement; D010064:Embryo Implantation / Q000502:physiology*; D047108:Embryonic Development; D005260:Female; D027261:Fusion Regulatory Protein-1 / Q000378:metabolism; D006801:Humans; D007930:Leucine / Q000378:metabolism; D051379:Mice; D011247:Pregnancy; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism; D014599:Uterus / Q000378:metabolism
chemical_list: D026905:Amino Acid Transport Systems; D000596:Amino Acids; D027261:Fusion Regulatory Protein-1; D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D007930:Leucine