Human Reproduction Update Advance Access originally published online on October 26, 2005
Human Reproduction Update 2006 12(2):145-157; doi:10.1093/humupd/dmi044
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System B0,+ amino acid transport regulates the penetration stage of blastocyst implantation with possible long-term developmental consequences through adulthood
1 Department of Biochemistry, 2 Department of Obstetrics and Gynecology, Midwestern University, Downers Grove, IL and 3 Department of Internal Medicine, Walter Reed Army Medical Center, Washington, DC, USA
4 To whom correspondence should be addressed at: Department of Biochemistry, Midwestern University, 555 31st Street, Downers Grove, IL 60515, USA. E-mail: lvanwi{at}midwestern.edu
Submitted on July 27, 2005; resubmitted on September 13, 2005; accepted on September 26, 2005
Amino acid transport system B0,+ 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 B0,+ 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 B0,+ becomes inactive in blastocysts a few hours before implantation in vivo. System B0,+ can, however, be activated in preimplantation blastocysts by physical stimuli. The onset of trophoblast motility should provide the physiological physical stimulus activating system B0,+ in blastocysts in vivo. Activation of system B0,+ 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 B0,+ regulation of these developmental processes likely influences placentation and subsequent embryo nutrition, birth weight and risk of developing metabolic syndrome and obesity.
Key words: amino acid transport systems / embryo implantation / human development / metabolic syndrome / small for gestational age
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