Amino acid transporter expression in the endometrium and conceptus membranes during early equine pregnancy
Charlotte Gibson A B , Marta de Ruijter-Villani A , Jolanda Rietveld A and Tom A. E. Stout AA Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 114, 3584 CM Utrecht, Netherlands.
B Corresponding author. Email: c.m.e.gibson@uu.nl
Reproduction, Fertility and Development 30(12) 1675-1688 https://doi.org/10.1071/RD17352
Submitted: 5 September 2017 Accepted: 7 May 2018 Published: 15 June 2018
Abstract
Maternally derived amino acids (AA) are essential for early conceptus development, and specific transporters enhance histotrophic AA content during early ruminant pregnancy. In the present study we investigated AA transporter expression in early equine conceptuses and endometrium, during normal pregnancy and after induction of embryo–uterus asynchrony. ‘Normal’ conceptuses and endometrium were recovered on Days 7, 14, 21 and 28 after ovulation. To investigate asynchrony, Day 8 embryos were transferred to recipient mares on Day 8 or Day 3, and conceptuses were recovered 6 or 11 days later. Endometrial expression of AA transporters solute carrier family 38 member 2 (SLC38A2), solute carrier family 1 members 4 and 5 (SLC1A4 and SLC1A5) increased during early pregnancy, whereas solute carrier family 7 member 8 (SLC7A8), solute carrier family 43 member 2 (SLC43A2) and solute carrier family 7 member 1 (SLC7A1) SLC7A8, SLC43A2 and SLC7A1 expression decreased and the expression of solute carrier family 1 member 1(SLC1A1) and solute carrier family 7 member 2 (SLC7A2) was unaffected. In conceptus membranes, most transporters studied were upregulated, either after Day 14 (solute carrier family 7 member 5 – SLC7A5, SLC38A2, SLC1A4, SLC1A5 and SLC7A1) or Day 21 (SLC43A2 and SLC7A2). Asynchronous ET indicated that endometrial SLC1A5, SLC1A1 and SLC7A8 are primarily regulated by conceptus factors and/or longer exposure to progesterone. In conclusion, AA transporters are expressed in early equine conceptus membranes and endometrium in specific spatiotemporal patterns. Because conceptuses express a wider range of transporters than the endometrium, we speculate that the equine yolk sac has recruited AA transporters to ensure adequate nutrient provision during an unusually long preimplantation period.
References
Acker, D. A., Curran, S., Bersu, E. T., and Ginther, O. J. (2001). Morphologic stages of the equine embryo proper on Days 17 to 40 after ovulation. Am. J. Vet. Res. 62, 1358–1364.| Morphologic stages of the equine embryo proper on Days 17 to 40 after ovulation.Crossref | GoogleScholarGoogle Scholar |
Allen, W. R., and Wilsher, S. (2009). A review of implantation and early placentation in the mare. Placenta 30, 1005–1015.
| A review of implantation and early placentation in the mare.Crossref | GoogleScholarGoogle Scholar |
Allen, W. R., Hamilton, D. W., and Moor, R. M. (1973). The origin of equine endometrial cups. II. Invasion of the endometrium by trophoblast. Anat. Rec. 177, 485–501.
| The origin of equine endometrial cups. II. Invasion of the endometrium by trophoblast.Crossref | GoogleScholarGoogle Scholar |
Allen, W. R., Kölling, M., and Wilsher, S. (2007). An interesting case of early pregnancy loss in a mare with persistent endometrial cups. Equine Vet. Educ. 19, 539–544.
| An interesting case of early pregnancy loss in a mare with persistent endometrial cups.Crossref | GoogleScholarGoogle Scholar |
Battaglia, F. C., and Regnault, T. R. H. (2001). Placental transport and metabolism of amino acids. Placenta 22, 145–161.
| Placental transport and metabolism of amino acids.Crossref | GoogleScholarGoogle Scholar |
Bazer, F. W., Spencer, T. E., Johnson, G. A., Burghardt, R. C., and Wu, G. (2009). Comparative aspects of implantation. Reproduction 138, 195–209.
| Comparative aspects of implantation.Crossref | GoogleScholarGoogle Scholar |
Bazer, F. W., Johnson, G. A., and Wu, G. (2015). Amino acids and conceptus development during the peri-implantation period of pregnancy. In ‘Cell Signaling During Mammalian Early Embryo Development’. (Eds H. J. Leese and D. R. Brison.) pp. 23–52. (Springer: New York.)
Budik, S., Walter, I., Tschulenk, W., Helmreich, M., Deichsel, K., Pittner, F., and Aurich, C. (2008). Significance of aquaporins and sodium potassium ATPase subunits for expansion of the early equine conceptus. Reproduction 135, 497–508.
| Significance of aquaporins and sodium potassium ATPase subunits for expansion of the early equine conceptus.Crossref | GoogleScholarGoogle Scholar |
Cleal, J. K., and Lewis, R. M. (2008). The mechanisms and regulation of placental amino acid transport to the human foetus. J. Neuroendocrinol. 20, 419–426.
| The mechanisms and regulation of placental amino acid transport to the human foetus.Crossref | GoogleScholarGoogle Scholar |
de Ruijter-Villani, M., van Tol, H. T. A., and Stout, T. A. E. (2015a). Effect of pregnancy on endometrial expression of luteolytic pathway components in the mare. Reprod. Fertil. Dev. 27, 834–845.
| Effect of pregnancy on endometrial expression of luteolytic pathway components in the mare.Crossref | GoogleScholarGoogle Scholar |
de Ruijter-Villani, M., Deelen, C., and Stout, T. A. E. (2015b). Expression of leukaemia inhibitory factor at the conceptus–maternal interface during preimplantation development and in the endometrium during the oestrous cycle in the mare. Reprod. Fertil. Dev. 28, 1642–1651.
| Expression of leukaemia inhibitory factor at the conceptus–maternal interface during preimplantation development and in the endometrium during the oestrous cycle in the mare.Crossref | GoogleScholarGoogle Scholar |
Filant, J., and Spencer, T. E. (2014). Uterine glands: biological roles in conceptus implantation, uterine receptivity and decidualization. Int. J. Dev. Biol. 58, 107–116.
| Uterine glands: biological roles in conceptus implantation, uterine receptivity and decidualization.Crossref | GoogleScholarGoogle Scholar |
Forde, N., Simintiras, C. A., Sturmey, R., Mamo, S., Kelly, A. K., Spencer, T. E., Bazer, F. W., and Lonergan, P. (2014). Amino acids in the uterine luminal fluid reflects the temporal changes in transporter expression in the endometrium and conceptus during early pregnancy in cattle. PLoS One 9, e100010.
| Amino acids in the uterine luminal fluid reflects the temporal changes in transporter expression in the endometrium and conceptus during early pregnancy in cattle.Crossref | GoogleScholarGoogle Scholar |
Gaivão, M. M. F., Rambags, B. P. B., and Stout, T. A. E. (2014). Gastrulation and the establishment of the three germ layers in the early horse conceptus. Theriogenology 82, 354–365.
| Gastrulation and the establishment of the three germ layers in the early horse conceptus.Crossref | GoogleScholarGoogle Scholar |
Gao, H., Wu, G., Spencer, T. E., Johnson, G. A., Li, X., and Bazer, F. W. (2009a). Select nutrients in the ovine uterine lumen. I. Amino acids, glucose, and ions in uterine lumenal flushings of cyclic and pregnant ewes. Biol. Reprod. 80, 86–93.
| Select nutrients in the ovine uterine lumen. I. Amino acids, glucose, and ions in uterine lumenal flushings of cyclic and pregnant ewes.Crossref | GoogleScholarGoogle Scholar |
Gao, H., Wu, G., Spencer, T. E., Johnson, G. A., and Bazer, F. W. (2009b). Select nutrients in the ovine uterine lumen. IV. Expression of neutral and acidic amino acid transporters in ovine uteri and peri-implantation conceptuses. Biol. Reprod. 80, 1196–1208.
| Select nutrients in the ovine uterine lumen. IV. Expression of neutral and acidic amino acid transporters in ovine uteri and peri-implantation conceptuses.Crossref | GoogleScholarGoogle Scholar |
Gao, H., Wu, G., Spencer, T. E., Johnson, G. A., and Bazer, F. W. (2009c). Select nutrients in the ovine uterine lumen. III. Cationic amino acid transporters in the ovine uterus and peri-implantation conceptuses. Biol. Reprod. 80, 602–609.
| Select nutrients in the ovine uterine lumen. III. Cationic amino acid transporters in the ovine uterus and peri-implantation conceptuses.Crossref | GoogleScholarGoogle Scholar |
Gibson, C., de Ruijter-Villani, M., and Stout, T. A. E. (2017). Negative uterine asynchrony retards early equine conceptus development and upregulation of placental imprinted genes. Placenta 57, 175–182.
| Negative uterine asynchrony retards early equine conceptus development and upregulation of placental imprinted genes.Crossref | GoogleScholarGoogle Scholar |
Ginther, O. J. (1998). Equine pregnancy: physical interactions between uterus and conceptus. AAEP Proc. 44, 73–103.
Grillo, M. A., Lanza, A., and Colombatto, S. (2008). Transport of amino acids through the placenta and their role. Amino Acids 34, 517–523.
| Transport of amino acids through the placenta and their role.Crossref | GoogleScholarGoogle Scholar |
Groebner, A. E., Rubio-Aliaga, I., Schulke, K., Reichenbach, H. D., Daniel, H., Wolf, E., Meyer, H. H. D., and Ulbrich, S. E. (2011). Increase of essential amino acids in the bovine uterine lumen during preimplantation development. Reproduction 141, 685–695.
| Increase of essential amino acids in the bovine uterine lumen during preimplantation development.Crossref | GoogleScholarGoogle Scholar |
Hyde, R., Taylor, P. M., and Hundal, H. S. (2003). Amino acid transporters: roles in amino acid sensing and signalling in animal cells. Biochem. J. 373, 1–18.
| Amino acid transporters: roles in amino acid sensing and signalling in animal cells.Crossref | GoogleScholarGoogle Scholar |
Jones, H. N., Powell, T. L., and Jansson, T. (2007). Regulation of placental nutrient transport – a review. Placenta 28, 763–774.
| Regulation of placental nutrient transport – a review.Crossref | GoogleScholarGoogle Scholar |
Lager, S., and Powell, T. L. (2012). Regulation of nutrient transport across the placenta. J. Pregnancy 2012, 179827.
| Regulation of nutrient transport across the placenta.Crossref | GoogleScholarGoogle Scholar |
Martin, P. M., Sutherland, A. E., and Van Winkle, L. J. (2003). Amino acid transport regulates blastocyst implantation. Biol. Reprod. 69, 1101–1108.
| Amino acid transport regulates blastocyst implantation.Crossref | GoogleScholarGoogle Scholar |
Moe, A. J. (1995). Placental amino acid transport. Am. J. Physiol. Cell Physiol. 268, C1321–C1331.
| Placental amino acid transport.Crossref | GoogleScholarGoogle Scholar |
Morris, L. H. A., and Allen, W. R. (2002). Reproductive efficiency of intensively managed thoroughbred mares in Newmarket. Equine Vet. J. 34, 51–60.
| Reproductive efficiency of intensively managed thoroughbred mares in Newmarket.Crossref | GoogleScholarGoogle Scholar |
Oriol, J. G., Sharom, F. J., and Betteridge, K. J. (1993). Developmentally regulated changes in the glycoproteins of the equine embryonic capsule. J. Reprod. Fertil. 99, 653–664.
| Developmentally regulated changes in the glycoproteins of the equine embryonic capsule.Crossref | GoogleScholarGoogle Scholar |
Regnault, T. R. H., de Vrijer, B., and Battaglia, F. C. (2002). Transport and metabolism of amino acids in placenta. Endocrine 19, 23–41.
| Transport and metabolism of amino acids in placenta.Crossref | GoogleScholarGoogle Scholar |
Sandra, O., Mansouri-Attia, N., and Lea, R. G. (2011). Novel aspects of endometrial function: a biological sensor of embryo quality and driver of pregnancy success. Reprod. Fertil. Dev. 24, 68–79.
| Novel aspects of endometrial function: a biological sensor of embryo quality and driver of pregnancy success.Crossref | GoogleScholarGoogle Scholar |
Stout, T. A. E. (2016). Embryo–maternal communication during the first 4 weeks of equine pregnancy. Theriogenology 86, 349–354.
| Embryo–maternal communication during the first 4 weeks of equine pregnancy.Crossref | GoogleScholarGoogle Scholar |
Van Winkle, L. J. (2001). Amino acid transport regulation and early embryo development. Biol. Reprod. 64, 1–12.
| Amino acid transport regulation and early embryo development.Crossref | GoogleScholarGoogle Scholar |
Vandesompele, J., De Preter, K., Pattyn, F., Poppe, B., Van Roy, N., De Paepe, A., and Speleman, F. (2002). Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 3, research0034.1–0034.11.
| Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes.Crossref | GoogleScholarGoogle Scholar |
Waelchli, R. O., Gerber, D., Volkmann, D. H., and Betteridge, K. J. (1996). Changes in the osmolality of equine blastocyst fluid between Days 11 and 25 of pregnancy. Theriogenology 45, 290.
| Changes in the osmolality of equine blastocyst fluid between Days 11 and 25 of pregnancy.Crossref | GoogleScholarGoogle Scholar |
Waelchli, R. O., MacPhee, D. J., Kidder, G. M., and Betteridge, K. J. (1997). Evidence for the presence of sodium- and potassium-dependent adenosine triphosphatase alpha1 and beta1 subunit isoforms and their probable role in blastocyst expansion in the preattachment horse conceptus. Biol. Reprod. 57, 630–640.
| Evidence for the presence of sodium- and potassium-dependent adenosine triphosphatase alpha1 and beta1 subunit isoforms and their probable role in blastocyst expansion in the preattachment horse conceptus.Crossref | GoogleScholarGoogle Scholar |
Walter, I., Tschulenk, W., Budik, S., and Aurich, C. (2010). Transmission electron microscopy (TEM) of equine conceptuses at 14 and 16 days of gestation. Reprod. Fertil. Dev. 22, 405–415.
| Transmission electron microscopy (TEM) of equine conceptuses at 14 and 16 days of gestation.Crossref | GoogleScholarGoogle Scholar |
Wilsher, S., and Allen, W. R. (2009). Uterine influences on embryogenesis and early placentation in the horse revealed by transfer of Day 10 embryos to Day 3 recipient mares. Reproduction 137, 583–593.
| Uterine influences on embryogenesis and early placentation in the horse revealed by transfer of Day 10 embryos to Day 3 recipient mares.Crossref | GoogleScholarGoogle Scholar |
Wilsher, S., Clutton-Brock, A., and Allen, W. R. (2010). Successful transfer of Day 10 horse embryos: influence of donor–recipient asynchrony on embryo development. Reproduction 139, 575–585.
| Successful transfer of Day 10 horse embryos: influence of donor–recipient asynchrony on embryo development.Crossref | GoogleScholarGoogle Scholar |
Wu, G. (2009). Amino acids: metabolism, functions, and nutrition. Amino Acids 37, 1–17.
| Amino acids: metabolism, functions, and nutrition.Crossref | GoogleScholarGoogle Scholar |
Zavy, J. T., Mayer, R., Vernon, M. W., Bazer, F. W., and Sharp, D. C. (1979). An investigation of the uterine luminal environment of non-pregnant and pregnant pony mares. J. Reprod. Fertil. Suppl. 27, 403–411.