Leucine and arginine regulate trophoblast motility through mTOR-dependent and independent pathways in the preimplantation mouse embryo
| Autor: | Isabel Gonzalez, Carol Burdsal, Jennifer L. Sloan, Ann Sutherland, Sela Mager, Thurl E. Harris, Patrick M. Martin |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Time Factors Amino Acid Transport Systems Transcription Genetic Arginine Fluorescent Antibody Technique mTORC1 Chorionic Gonadotropin Plasma Membrane Neurotransmitter Transport Proteins Mammalian reproduction Mice 0302 clinical medicine Cell Movement Phosphorylation Mice Inbred ICR 0303 health sciences TOR Serine-Threonine Kinases Implantation Trophoblasts Cell biology Protein Transport medicine.anatomical_structure Biochemistry embryonic structures mTOR Amino acids Female Signal transduction Signal Transduction Motility Mechanistic Target of Rapamycin Complex 1 Biology Models Biological Article 03 medical and health sciences Leucine medicine Animals Humans Blastocyst Molecular Biology PI3K/AKT/mTOR pathway 030304 developmental biology Sirolimus Proteins Trophoblast Biological Transport Blastocyst activation Cell Biology Enzyme Activation Multiprotein Complexes Protein Biosynthesis 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Developmental Biology. 361(2):286-300 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2011.10.021 |
| Popis: | Uterine implantation is a critical element of mammalian reproduction and is a tightly and highly coordinated event. An intricate and reciprocal uterine-embryo dialog exists to synchronize uterine receptivity with the concomitant activation of the blastocyst, maximizing implantation success. While a number of pathways involved in regulating uterine receptivity have been identified in the mouse, less is understood about blastocyst activation, the process by which the trophectoderm (TE) receives extrinsic cues that initiate new characteristics essential for implantation. Amino acids (AA) have been found to regulate blastocyst activation and TE motility . In particular, we find that arginine and leucine alone are necessary and sufficient to induce TE motility. Both arginine and leucine act individually and additively to propagate signals that are dependent on the activity of the mammalian target of rapamycin complex 1 (mTORC1). The activities of the well-established downstream targets of mTORC1, p70S6K and 4EBP, do not correlate with trophoblast motility, suggesting that an independent-rapamycin-sensitive pathway operates to induce trophoblast motility, or that other, parallel amino acid-dependent pathways are also involved. We find that endogenous uterine factors act to induce mTORC1 activation and trophoblast motility at a specific time during pregnancy, and that this uterine signal is later than the previously defined signal that induces the attachment reaction. matured blastocysts exhibit competence to respond to an 8-hour AA stimulus by activating mTOR and subsequently undergoing trophoblast outgrowth by the morning of day 4.5 of pregnancy, but not on day 3.5. By the late afternoon of day 4.5, the embryos no longer require any exposure to AA to undergo trophoblast outgrowth , demonstrating the existence and timing of an equivalent signal. These results suggest that there are two separate uterine signals regulating implantation, one that primes the embryo for the attachment reaction and another that activates mTOR and initiates invasive behavior.► Arginine and leucine are necessary and sufficient to induce trophoblast motility. ► Arginine and leucine have both mTORC1-dependent and independent actions. ► p70S6K or 4EBP activity do not correlate with motility suggesting a separate pathway. ► mTOR activation suggests uterine factors induce mTORC1 regulated motility. ► Amino acids may be components of the uterine-embryo implantation crosstalk. |
| Databáze: | OpenAIRE |
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