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Erschienen in: Journal of Assisted Reproduction and Genetics 3/2012

01.03.2012 | Embryo Biology

Dipeptide forms of glycine support mouse preimplantation embryo development in vitro and provide protection against high media osmolality

verfasst von: Molly Moravek, Senait Fisseha, Jason E. Swain

Erschienen in: Journal of Assisted Reproduction and Genetics | Ausgabe 3/2012

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Abstract

Purpose

To examine potential benefits of dipeptide forms of amino acids for embryo culture by determining ability of dipeptide glycine forms to support embryo development, act as osmolytes, and reduce ammonia production.

Methods

Frozen thawed 1-cell mouse embryos were cultured in media with varying osmolality with glycine and dipeptide forms of glycine and development assessed. Ammonia levels were measured in various media.

Results

Dipeptide forms of glycine, alanyl- and glycyl-glycine, can support mouse embryo development in vitro. Additionally, dipeptide glycine can act as an organic osmolyte in developing embryos, permitting blastocyst formation in high osmolality media. Interestingly, as evidenced by decreased embryo development, dipeptides are not as efficient as osmolytes as their constituent individual amino acids. Dipeptide glycine produced less ammonia than glycine.

Conclusion

Though dipeptides can provide osmoregulation in preimplantation embryos, efficacy may be lower than individual amino acids. The mechanism by which embryos transport and utilize dipeptide amino acids remains to be identified.
Literatur
1.
Zurück zum Zitat Gardner DK, Lane M. Culture Systems for Human Embryos. In: Gardner DK, editor. Textbook of Assisted Reproductive Technologies. Boca Raton: Informa UK Ltd; 2009. p. 219–40. Gardner DK, Lane M. Culture Systems for Human Embryos. In: Gardner DK, editor. Textbook of Assisted Reproductive Technologies. Boca Raton: Informa UK Ltd; 2009. p. 219–40.
2.
Zurück zum Zitat Gardner DK, Lane M. Alleviation of the ′2-cell block’ and development to the blastocyst of CF1 mouse embryos: role of amino acids, EDTA and physical parameters. Hum Reprod. 1996;11(12):2703–12.PubMed Gardner DK, Lane M. Alleviation of the ′2-cell block’ and development to the blastocyst of CF1 mouse embryos: role of amino acids, EDTA and physical parameters. Hum Reprod. 1996;11(12):2703–12.PubMed
3.
Zurück zum Zitat Lane M, Gardner DK. Differential regulation of mouse embryo development and viability by amino acids. J Reprod Fertil. 1997;109(1):153–64.PubMedCrossRef Lane M, Gardner DK. Differential regulation of mouse embryo development and viability by amino acids. J Reprod Fertil. 1997;109(1):153–64.PubMedCrossRef
4.
Zurück zum Zitat McKiernan SH, Clayton MK, Bavister BD. Analysis of stimulatory and inhibitory amino acids for development of hamster one-cell embryos in vitro. Mol Reprod Dev. 1995;42(2):188–99.PubMedCrossRef McKiernan SH, Clayton MK, Bavister BD. Analysis of stimulatory and inhibitory amino acids for development of hamster one-cell embryos in vitro. Mol Reprod Dev. 1995;42(2):188–99.PubMedCrossRef
5.
Zurück zum Zitat Dawson KM, Baltz JM. Organic osmolytes and embryos: substrates of the Gly and beta transport systems protect mouse zygotes against the effects of raised osmolarity. Biol Reprod. 1997;56(6):1550–8.PubMedCrossRef Dawson KM, Baltz JM. Organic osmolytes and embryos: substrates of the Gly and beta transport systems protect mouse zygotes against the effects of raised osmolarity. Biol Reprod. 1997;56(6):1550–8.PubMedCrossRef
6.
Zurück zum Zitat Hay-Schmidt A. The influence of osmolality on mouse two-cell development. J Assist Reprod Genet. 1993;10(1):95–8.PubMedCrossRef Hay-Schmidt A. The influence of osmolality on mouse two-cell development. J Assist Reprod Genet. 1993;10(1):95–8.PubMedCrossRef
7.
Zurück zum Zitat Miyoshi K, Funahashi H, Okuda K, et al. Development of rat one-cell embryos in a chemically defined medium: effects of glucose, phosphate and osmolarity. J Reprod Fertil. 1994;100(1):21–6.PubMedCrossRef Miyoshi K, Funahashi H, Okuda K, et al. Development of rat one-cell embryos in a chemically defined medium: effects of glucose, phosphate and osmolarity. J Reprod Fertil. 1994;100(1):21–6.PubMedCrossRef
8.
Zurück zum Zitat Swain J, Cabrera L, Xu X, et al. Environmental factors and manipulations during preparation influence embryo culture media osmolality. Fertil Steril. 2010;94(4):s32.CrossRef Swain J, Cabrera L, Xu X, et al. Environmental factors and manipulations during preparation influence embryo culture media osmolality. Fertil Steril. 2010;94(4):s32.CrossRef
9.
Zurück zum Zitat Baltz JM, Tartia AP. Cell volume regulation in oocytes and early embryos: connecting physiology to successful culture media. Hum Reprod Update. 2010;16(2):166–76.PubMedCrossRef Baltz JM, Tartia AP. Cell volume regulation in oocytes and early embryos: connecting physiology to successful culture media. Hum Reprod Update. 2010;16(2):166–76.PubMedCrossRef
10.
Zurück zum Zitat Dawson KM, Collins JL, Baltz JM. Osmolarity-dependent glycine accumulation indicates a role for glycine as an organic osmolyte in early preimplantation mouse embryos. Biol Reprod. 1998;59(2):225–32.PubMedCrossRef Dawson KM, Collins JL, Baltz JM. Osmolarity-dependent glycine accumulation indicates a role for glycine as an organic osmolyte in early preimplantation mouse embryos. Biol Reprod. 1998;59(2):225–32.PubMedCrossRef
11.
Zurück zum Zitat Hobbs JG, Kaye PL. Glycine transport in mouse eggs and preimplantation embryos. J Reprod Fertil. 1985;74(1):77–86.PubMedCrossRef Hobbs JG, Kaye PL. Glycine transport in mouse eggs and preimplantation embryos. J Reprod Fertil. 1985;74(1):77–86.PubMedCrossRef
12.
Zurück zum Zitat Hobbs JG, Kaye PL. Glycine and Na + transport in preimplantation mouse embryos. J Reprod Fertil. 1986;77(1):61–6.PubMedCrossRef Hobbs JG, Kaye PL. Glycine and Na + transport in preimplantation mouse embryos. J Reprod Fertil. 1986;77(1):61–6.PubMedCrossRef
13.
Zurück zum Zitat Hobbs JG, Kaye PL. Glycine uptake in pre-implantation mouse embryos: kinetics and the effects of external [Na+]. Reprod Fertil Dev. 1990;2(6):651–60.PubMedCrossRef Hobbs JG, Kaye PL. Glycine uptake in pre-implantation mouse embryos: kinetics and the effects of external [Na+]. Reprod Fertil Dev. 1990;2(6):651–60.PubMedCrossRef
14.
Zurück zum Zitat Van Winkle LJ, Haghighat N, Campione AL, et al. Glycine transport in mouse eggs and preimplantation conceptuses. Biochim Biophys Acta. 1988;941(2):241–56.PubMedCrossRef Van Winkle LJ, Haghighat N, Campione AL, et al. Glycine transport in mouse eggs and preimplantation conceptuses. Biochim Biophys Acta. 1988;941(2):241–56.PubMedCrossRef
15.
Zurück zum Zitat Hammer MA, Kolajova M, Leveille M, et al. Glycine transport by single human and mouse embryos. Hum Reprod. 2000;15(2):419–26.PubMedCrossRef Hammer MA, Kolajova M, Leveille M, et al. Glycine transport by single human and mouse embryos. Hum Reprod. 2000;15(2):419–26.PubMedCrossRef
16.
Zurück zum Zitat Lane M, Hooper K, Gardner DK. Effect of essential amino acids on mouse embryo viability and ammonium production. J Assist Reprod Genet. 2001;18(9):519–25.PubMedCrossRef Lane M, Hooper K, Gardner DK. Effect of essential amino acids on mouse embryo viability and ammonium production. J Assist Reprod Genet. 2001;18(9):519–25.PubMedCrossRef
17.
Zurück zum Zitat Gardner DK, Lane M. Amino acids and ammonium regulate mouse embryo development in culture. Biol Reprod. 1993;48(2):377–85.PubMedCrossRef Gardner DK, Lane M. Amino acids and ammonium regulate mouse embryo development in culture. Biol Reprod. 1993;48(2):377–85.PubMedCrossRef
18.
Zurück zum Zitat Lane M, Gardner DK. Increase in postimplantation development of cultured mouse embryos by amino acids and induction of fetal retardation and exencephaly by ammonium ions. J Reprod Fertil. 1994;102(2):305–12.PubMedCrossRef Lane M, Gardner DK. Increase in postimplantation development of cultured mouse embryos by amino acids and induction of fetal retardation and exencephaly by ammonium ions. J Reprod Fertil. 1994;102(2):305–12.PubMedCrossRef
19.
Zurück zum Zitat Lane M, Gardner DK. Ammonium induces aberrant blastocyst differentiation, metabolism, pH regulation, gene expression and subsequently alters fetal development in the mouse. Biol Reprod. 2003;69(4):1109–17.PubMedCrossRef Lane M, Gardner DK. Ammonium induces aberrant blastocyst differentiation, metabolism, pH regulation, gene expression and subsequently alters fetal development in the mouse. Biol Reprod. 2003;69(4):1109–17.PubMedCrossRef
20.
Zurück zum Zitat Zander DL, Thompson JG, Lane M. Perturbations in mouse embryo development and viability caused by ammonium are more severe after exposure at the cleavage stages. Biol Reprod. 2006;74(2):288–94.PubMedCrossRef Zander DL, Thompson JG, Lane M. Perturbations in mouse embryo development and viability caused by ammonium are more severe after exposure at the cleavage stages. Biol Reprod. 2006;74(2):288–94.PubMedCrossRef
21.
Zurück zum Zitat Biggers JD, McGinnis LK, Summers MC. Discrepancies between the effects of glutamine in cultures of preimplantation mouse embryos. Reprod Biomed Online. 2004;9(1):70–3.PubMedCrossRef Biggers JD, McGinnis LK, Summers MC. Discrepancies between the effects of glutamine in cultures of preimplantation mouse embryos. Reprod Biomed Online. 2004;9(1):70–3.PubMedCrossRef
22.
Zurück zum Zitat Christie A, Butler M. Glutamine-based dipeptides are utilized in mammalian cell culture by extracellular hydrolysis catalyzed by a specific peptidase. J Biotechnol. 1994;37(3):277–90.PubMedCrossRef Christie A, Butler M. Glutamine-based dipeptides are utilized in mammalian cell culture by extracellular hydrolysis catalyzed by a specific peptidase. J Biotechnol. 1994;37(3):277–90.PubMedCrossRef
23.
Zurück zum Zitat Eagle H. Utilization of dipeptides by mammalian cells in tissue culture. Proc Soc Exp Biol Med. 1955;89(1):96–9.PubMed Eagle H. Utilization of dipeptides by mammalian cells in tissue culture. Proc Soc Exp Biol Med. 1955;89(1):96–9.PubMed
24.
Zurück zum Zitat Roth E, Ollenschlager G, Hamilton G, et al. Influence of two glutamine-containing dipeptides on growth of mammalian cells. In Vitro Cell Dev Biol. 1988;24(7):696–8.PubMedCrossRef Roth E, Ollenschlager G, Hamilton G, et al. Influence of two glutamine-containing dipeptides on growth of mammalian cells. In Vitro Cell Dev Biol. 1988;24(7):696–8.PubMedCrossRef
25.
Zurück zum Zitat Biggers JD, McGinnis LK, Lawitts JA. Enhanced effect of glycyl-L-glutamine on mouse preimplantation embryos in vitro. Reprod Biomed Online. 2004;9(1):59–69.PubMedCrossRef Biggers JD, McGinnis LK, Lawitts JA. Enhanced effect of glycyl-L-glutamine on mouse preimplantation embryos in vitro. Reprod Biomed Online. 2004;9(1):59–69.PubMedCrossRef
26.
Zurück zum Zitat Summers MC, McGinnis LK, Lawitts JA, et al. Mouse embryo development following IVF in media containing either L-glutamine or glycyl-L-glutamine. Hum Reprod. 2005;20(5):1364–71.PubMedCrossRef Summers MC, McGinnis LK, Lawitts JA, et al. Mouse embryo development following IVF in media containing either L-glutamine or glycyl-L-glutamine. Hum Reprod. 2005;20(5):1364–71.PubMedCrossRef
27.
Zurück zum Zitat Quinn P, Kerin J, Warnes G. Improved pregnancy rate in human in vitro fertilization with the use of a medium based on the composition of human tubal fluid. Fertil Steril. 1985;44:493–8.PubMed Quinn P, Kerin J, Warnes G. Improved pregnancy rate in human in vitro fertilization with the use of a medium based on the composition of human tubal fluid. Fertil Steril. 1985;44:493–8.PubMed
28.
Zurück zum Zitat Hagemann LJ, Weilert LL, Beaumont SE, et al. Development of bovine embryos in single in vitro production (sIVP) systems. Mol Reprod Dev. 1998;51(2):143–7.PubMedCrossRef Hagemann LJ, Weilert LL, Beaumont SE, et al. Development of bovine embryos in single in vitro production (sIVP) systems. Mol Reprod Dev. 1998;51(2):143–7.PubMedCrossRef
29.
Zurück zum Zitat Hammer MA, Baltz JM. Betaine is a highly effective organic osmolyte but does not appear to be transported by established organic osmolyte transporters in mouse embryos. Mol Reprod Dev. 2002;62(2):195–202.PubMedCrossRef Hammer MA, Baltz JM. Betaine is a highly effective organic osmolyte but does not appear to be transported by established organic osmolyte transporters in mouse embryos. Mol Reprod Dev. 2002;62(2):195–202.PubMedCrossRef
30.
Zurück zum Zitat Hammer MA, Baltz JM. Beta-alanine but not taurine can function as an organic osmolyte in preimplantation mouse embryos cultured from fertilized eggs. Mol Reprod Dev. 2003;66(2):153–61.PubMedCrossRef Hammer MA, Baltz JM. Beta-alanine but not taurine can function as an organic osmolyte in preimplantation mouse embryos cultured from fertilized eggs. Mol Reprod Dev. 2003;66(2):153–61.PubMedCrossRef
31.
Zurück zum Zitat Richards T, Wang F, Liu L, et al. Rescue of postcompaction-stage mouse embryo development from hypertonicity by amino acid transporter substrates that may function as organic osmolytes. Biol Reprod. 2010;82(4):769–77.PubMedCrossRef Richards T, Wang F, Liu L, et al. Rescue of postcompaction-stage mouse embryo development from hypertonicity by amino acid transporter substrates that may function as organic osmolytes. Biol Reprod. 2010;82(4):769–77.PubMedCrossRef
32.
Zurück zum Zitat Steeves CL, Hammer MA, Walker GB, et al. The glycine neurotransmitter transporter GLYT1 is an organic osmolyte transporter regulating cell volume in cleavage-stage embryos. Proc Natl Acad Sci U S A. 2003;100(24):13982–7.PubMedCrossRef Steeves CL, Hammer MA, Walker GB, et al. The glycine neurotransmitter transporter GLYT1 is an organic osmolyte transporter regulating cell volume in cleavage-stage embryos. Proc Natl Acad Sci U S A. 2003;100(24):13982–7.PubMedCrossRef
33.
Zurück zum Zitat Steeves CL, Baltz JM. Regulation of intracellular glycine as an organic osmolyte in early preimplantation mouse embryos. J Cell Physiol. 2005;204(1):273–9.PubMedCrossRef Steeves CL, Baltz JM. Regulation of intracellular glycine as an organic osmolyte in early preimplantation mouse embryos. J Cell Physiol. 2005;204(1):273–9.PubMedCrossRef
34.
Zurück zum Zitat Tartia AP, Rudraraju N, Richards T, et al. Cell volume regulation is initiated in mouse oocytes after ovulation. Development. 2009;136(13):2247–54.PubMedCrossRef Tartia AP, Rudraraju N, Richards T, et al. Cell volume regulation is initiated in mouse oocytes after ovulation. Development. 2009;136(13):2247–54.PubMedCrossRef
35.
Zurück zum Zitat Van Winkle LJ, Campione AL, Farrington BH. Development of system B0,+ and a broad-scope Na(+)-dependent transporter of zwitterionic amino acids in preimplantation mouse conceptuses. Biochim Biophys Acta. 1990;1025(2):225–33.PubMedCrossRef Van Winkle LJ, Campione AL, Farrington BH. Development of system B0,+ and a broad-scope Na(+)-dependent transporter of zwitterionic amino acids in preimplantation mouse conceptuses. Biochim Biophys Acta. 1990;1025(2):225–33.PubMedCrossRef
36.
Zurück zum Zitat Fujiwara H. Membrane-bound peptidases regulate human extravillous trophoblast invasion. Placenta. 2007;28(Suppl A):S70–75.PubMedCrossRef Fujiwara H. Membrane-bound peptidases regulate human extravillous trophoblast invasion. Placenta. 2007;28(Suppl A):S70–75.PubMedCrossRef
37.
Zurück zum Zitat Fujiwara H, Higuchi T, Sato Y, et al. Regulation of human extravillous trophoblast function by membrane-bound peptidases. Biochim Biophys Acta. 2005;1751(1):26–32.PubMed Fujiwara H, Higuchi T, Sato Y, et al. Regulation of human extravillous trophoblast function by membrane-bound peptidases. Biochim Biophys Acta. 2005;1751(1):26–32.PubMed
38.
Zurück zum Zitat Frolund S, Holm R, Brodin B, et al. The proton-coupled amino acid transporter, SLC36A1 (hPAT1), transports Gly-Gly, Gly-Sar and other Gly-Gly mimetics. Br J Pharmacol. 2010;161(3):589–600.PubMedCrossRef Frolund S, Holm R, Brodin B, et al. The proton-coupled amino acid transporter, SLC36A1 (hPAT1), transports Gly-Gly, Gly-Sar and other Gly-Gly mimetics. Br J Pharmacol. 2010;161(3):589–600.PubMedCrossRef
39.
Zurück zum Zitat Hu Y, Ocheltree SM, Xiang J, et al. Glycyl-L-glutamine disposition in rat choroid plexus epithelial cells in primary culture: role of PEPT2. Pharm Res. 2005;22(8):1281–6.PubMedCrossRef Hu Y, Ocheltree SM, Xiang J, et al. Glycyl-L-glutamine disposition in rat choroid plexus epithelial cells in primary culture: role of PEPT2. Pharm Res. 2005;22(8):1281–6.PubMedCrossRef
40.
Zurück zum Zitat Atanassov A, Seiler N, Rebel G. Reduction of ammonia formation in cell cutlures by l-alanyl-l-glutamine requires optimization of the dipeptide concentration. J Biotechnol. 1998;62:159–62.CrossRef Atanassov A, Seiler N, Rebel G. Reduction of ammonia formation in cell cutlures by l-alanyl-l-glutamine requires optimization of the dipeptide concentration. J Biotechnol. 1998;62:159–62.CrossRef
41.
Zurück zum Zitat Van Winkle LJ, Campione AL. Development of amino acid transport system B0,+ in mouse blastocysts. Biochim Biophys Acta. 1987;925(2):164–74.PubMedCrossRef Van Winkle LJ, Campione AL. Development of amino acid transport system B0,+ in mouse blastocysts. Biochim Biophys Acta. 1987;925(2):164–74.PubMedCrossRef
42.
Zurück zum Zitat Van Winkle LJ, Campione AL, Kester SE. A possible effect of the Na + concentration in oviductal fluid on amino acid uptake by cleavage-stage mouse embryos. J Exp Zool. 1985;235(1):141–5.PubMedCrossRef Van Winkle LJ, Campione AL, Kester SE. A possible effect of the Na + concentration in oviductal fluid on amino acid uptake by cleavage-stage mouse embryos. J Exp Zool. 1985;235(1):141–5.PubMedCrossRef
43.
Zurück zum Zitat Moore K, Bondioli KR. Glycine and alanine supplementation of culture medium enhances development of in vitro matured and fertilized cattle embryos. Biol Reprod. 1993;48(4):833–40.PubMedCrossRef Moore K, Bondioli KR. Glycine and alanine supplementation of culture medium enhances development of in vitro matured and fertilized cattle embryos. Biol Reprod. 1993;48(4):833–40.PubMedCrossRef
44.
Zurück zum Zitat Lee ES, Fukui Y. Synergistic effect of alanine and glycine on bovine embryos cultured in a chemically defined medium and amino acid uptake by vitro-produced bovine morulae and blastocysts. Biol Reprod. 1996;55(6):1383–9.PubMedCrossRef Lee ES, Fukui Y. Synergistic effect of alanine and glycine on bovine embryos cultured in a chemically defined medium and amino acid uptake by vitro-produced bovine morulae and blastocysts. Biol Reprod. 1996;55(6):1383–9.PubMedCrossRef
Metadaten
Titel
Dipeptide forms of glycine support mouse preimplantation embryo development in vitro and provide protection against high media osmolality
verfasst von
Molly Moravek
Senait Fisseha
Jason E. Swain
Publikationsdatum
01.03.2012
Verlag
Springer US
Erschienen in
Journal of Assisted Reproduction and Genetics / Ausgabe 3/2012
Print ISSN: 1058-0468
Elektronische ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-011-9705-7

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