Abstract
In this review we discuss the beneficial effects of amino acid transport and metabolism on pre- and peri-implantation embryo development, and we consider how disturbances in these processes lead to undesirable health outcomes in adults. Proline, glutamine, glycine, and methionine transport each foster cleavage-stage development, whereas leucine uptake by blastocysts via transport system B0,+ promotes the development of trophoblast motility and the penetration of the uterine epithelium in mammalian species exhibiting invasive implantation. (Amino acid transport systems and transporters, such as B0,+, are often oddly named. The reader is urged to focus on the transporters’ functions, not their names.) B0,+ also accumulates leucine and other amino acids in oocytes of species with noninvasive implantation, thus helping them to produce proteins to support later development. This difference in the timing of the expression of system B0,+ is termed heterochrony—a process employed in evolution. Disturbances in leucine uptake via system B0,+ in blastocysts appear to alter the subsequent development of embryos, fetuses, and placentae, with undesirable consequences for offspring. These consequences may include greater adiposity, cardiovascular dysfunction, hypertension, neural abnormalities, and altered bone growth in adults. Similarly, alterations in amino acid transport and metabolism in pluripotent cells in the blastocyst inner cell mass likely lead to epigenetic DNA and histone modifications that produce unwanted transgenerational health outcomes. Such outcomes might be avoided if we learn more about the mechanisms of these effects.
Highlights
The variety of known functions of amino acid transport and metabolism supporting oocyte and early embryo development are quite remarkable
One or more of these Thr transporters may function for signaling as a transceptor [22], as well as by supplying the intracellular Thr metabolized for the specific epigenetic modifications needed to maintain mES cell proliferation and pluripotency
We propose that endogenous Glu production from Lys in human as well as mouse inner cell masses (ICMs) cells, and the release of this pool of Glu from the cells, help to maintain their pluripotency and proliferation
Summary
The variety of known functions of amino acid transport and metabolism supporting oocyte and early embryo development are quite remarkable. Amino acids and their metabolites resemble classical signaling molecules, such as hormones and growth factors, as well as the substances needed to regulate histone and DNA epigenetic modifications [1,2]. H3K4me supports ES and ICM cell proliferation and pluripotency in mice, humans, and probably other species [1] Leucine uptake initiates mTOR1 signaling; Tryptophan removal suppresses T-cells mTOR1, nitric oxide, polyamine signaling mTOR1, nitric oxide, polyamine signaling Transceptor; 2 Formation of
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