Amino Acid Transport Regulates Blastocyst Implantation

• Published in: Biology of reproduction 2003-10, Vol.69 (4), p.1101-1108
• Main Authors: MARTIN, Patrick M, SUTHERLAND, Ann E, VAN WINKLE, Lon J
• Format: Article
• Language: English
• Subjects: Amino Acids - metabolism; Animals; Biological and medical sciences; Biological Transport, Active - physiology; Cell Movement; Embryo Implantation - physiology; Embryology: invertebrates and vertebrates. Teratology; Female; Fundamental and applied biological sciences. Psychology; Leucine - metabolism; Mice; Molecular embryology; Nitric Oxide - metabolism; Placenta - metabolism; Pregnancy; Signal Transduction; Sirolimus - metabolism; Sirolimus - pharmacology; Trophoblasts - cytology; Trophoblasts - drug effects; Trophoblasts - metabolism
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.103.018010

Mouse blastocyst outgrowth in vitro and probably implantation in vivo require amino acid signaling via the target of rapamycin (TOR) pathway. This signaling does not simply support protein synthesis and trophoblast differentiation. Rather, it regulates development of trophoblast protrusive activity and may act as a developmental checkpoint for implantation. Moreover, intracellular amino acids per se are insufficient to elicit TOR signaling. Instead, de novo transport of amino acids, and particularly of leucine, stimulate mTOR activity at the blastocyst stage. The activity of the broad-scope and yet leucine-selective amino acid transport system B 0,+ could produce such increases in intracellular amino acid concentrations. For example, system B 0,+ uses a Na + gradient to drive amino acid uptake, and the Na + concentration in uterine secretions increases by nearly two-fold about 18 h before implantation. The resultant mTOR signaling could trigger polyamine, insulin-like growth factor II, and nitric oxide production in blastocysts and the increased cell motility sometimes associated with synthesis of these bioactive molecules.