Biosynthesis of oestrogen by the early equine embryo proper
James I. Raeside A B , Heather L. Christie A , Rudolf O. Waelchli A and Keith J. Betteridge A
+ Author Affiliations
- Author Affiliations
A Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G2W1, Canada.
B Corresponding author. Email: jraeside@uoguelph.ca
Reproduction, Fertility and Development 24(8) 1071-1078 https://doi.org/10.1071/RD11275
Submitted: 21 June 2011 Accepted: 7 March 2012 Published: 10 April 2012
Abstract
The embryo proper in early equine pregnancy has recently been shown to have a remarkable capacity for metabolism of oestrogens. High concentrations of oestrogens in yolk-sac fluid could provide substrate for local metabolism in tissues of the embryo proper and this activity could have significance for early development. Due to the high level of oestrogen metabolism in the embryo proper we examined the possibility that it could also biosynthesise oestrogens. Conceptuses were collected in the fourth week of pregnancy (n = 23) and the embryo was separated from extraembryonic tissues for incubation with [3H]androstenedione. Steroids were recovered from media by solid-phase extraction and eluted as unconjugated and conjugated fractions. Profiles of free and sulfoconjugated fractions, as well as the phenolic steroids extracted from them, were obtained by chromatography. Oestrone and oestradiol were seen clearly, indicating oestrogen biosynthesis, and the presence of more polar products, arising from metabolism of the primary oestrogens, gave further evidence that the embryo was capable of oestrogen biosynthesis. Aromatase activity was also demonstrated by detection of tritium loss, as 3H2O, from incubations (n = 3) with [1β-3H]androstenedione. It is suggested that its oestrogen biosynthesis may have significance for the remarkable development of the vasculature in the embryo proper at this stage.
Additional keywords: early pregnancy, oestradiol, oestrone, vasculogenesis.
References
Acker, M. S., 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 | 1:STN:280:DC%2BD3Mrht1Citg%3D%3D&md5=9f65caa7e8f5b9d8f06a90dad511ba2eCAS |
Albuquerque, M. L., Akiyama, S. K., and Schnaper, H. W. (1998). Basic fibroblast growth factor release by human coronary artery endothelial cells is enhanced by matrix proteins, 17beta-oestradiol and a PKC signalling pathway. Exp. Cell Res. 245, 163–169.
| Basic fibroblast growth factor release by human coronary artery endothelial cells is enhanced by matrix proteins, 17beta-oestradiol and a PKC signalling pathway.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXnvVertrw%3D&md5=cf50944ced02f9ed18e1ba068ee0fd3fCAS | 9828112PubMed |
Bazer, F. W., and Thatcher, W. W. (1977). Theory of maternal recognition of pregnancy in swine based on oestrogen-controlled endocrine versus exocrine secretion of prostaglandin F2α by the uterine endometrium. Prostaglandins 14, 397–401.
| Theory of maternal recognition of pregnancy in swine based on oestrogen-controlled endocrine versus exocrine secretion of prostaglandin F2α by the uterine endometrium.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE2sXls1WrtL8%3D&md5=0c4fc02f83c4b8150e44b69741e626b9CAS | 897228PubMed |
Betteridge, K. J., Waelchli, R. O., LaMarre, J., Alexander, S. L., Schand, N. A., Roud, H. K., Ruddock, W. D. J., Crews, L. J. E., Gillies, L. K., and Kee, G. (2000). Conceptus contents and coverings in relation to the maintenance of early pregnancy in the mare. Havemeyer Fdn. Monogr. Ser. No. 2 , 17–19.
Burrows, H. (1949). ‘Biological Actions of Sex Hormones’. 2nd edn. (Cambridge University Press: Cambridge.)
Cattaneo, M. G., Lucci, G., and Vincentini, L. M. (2009). Oxytocin stimulates in vitro angiogenesis via a Pyk-2/Src-dependent mechanism. Exp. Cell Res. 315, 3210–3219.
| Oxytocin stimulates in vitro angiogenesis via a Pyk-2/Src-dependent mechanism.Crossref | GoogleScholarGoogle Scholar | 19563802PubMed |
Charnock-Jones, D., Sharkey, A., Rajput-Williams, J., Burch, D., Schofield, J., Fountain, S., Boocock, C., and Smith, S. (1993). Identification and localization of alternatively spliced mRNA for vascular endothelial growth factor in human uterus and oestrogen regulation in endometrial carcinoma cell lines. Biol. Reprod. 48, 1120–1128.
| Identification and localization of alternatively spliced mRNA for vascular endothelial growth factor in human uterus and oestrogen regulation in endometrial carcinoma cell lines.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXks1eqt7g%3D&md5=588c2bfd8a8c5401820ab246cbb79209CAS | 8481475PubMed |
Choi, S. J., Anderson, G. B., and Roser, J. F. (1997). Production of free oestrogens and oestrogen conjugates by the preimplantation equine embryo. Theriogenology 47, 457–466.
| Production of free oestrogens and oestrogen conjugates by the preimplantation equine embryo.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXhvValu7c%3D&md5=7bec86efc75fb67faa4975008f6ca887CAS | 16727998PubMed |
Cox, J. (1975). Oestrone and equilin in the plasma of the pregnant mare. J. Reprod. Fertil. Suppl. 23, 414–420.
Cullinan-Bove, K., and Koos, R. (1993). Vascular endothelial growth factor/vascular permeability factor expression in the rat uterus: rapid stimulation by oestrogen correlates with oestrogen-induced increases in uterine capillary permeability and growth. Endocrinology 133, 829–837.
| Vascular endothelial growth factor/vascular permeability factor expression in the rat uterus: rapid stimulation by oestrogen correlates with oestrogen-induced increases in uterine capillary permeability and growth.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXmtFyhurc%3D&md5=5b303d8b0f3bd69f2863142d9a5c71eeCAS | 8344219PubMed |
Dadiani, M., Seger, D., Kreizman, T., Badikhi, D., Margalit, R., Eilam, R., and Degani, H. (2009). Oestrogen regulation of vascular endothelial growth factor in breast cancer in vitro and in vivo: the role of oestrogen receptor alpha and c-Myc. Endocr. Relat. Cancer 16, 819–834.
| Oestrogen regulation of vascular endothelial growth factor in breast cancer in vitro and in vivo: the role of oestrogen receptor alpha and c-Myc.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXht1GnurnN&md5=7340d8493fb10df8931619c4ce8c101eCAS | 19398483PubMed |
Flood, P. F., Betteridge, K. J., and Irvine, D. S. (1987). Oestrogens and androgens in blastocoelic fluid and cultures of cells from equine conceptuses of 10–22 days gestation. J. Reprod. Fertil. Suppl. 27, 414–420.
Gaillard, J. L., and Silberzahn, P. (1987). Aromatization of 19-norandrogens by equine testicular microsomes. J. Biol. Chem. 262, 5717–5722.
| 1:CAS:528:DyaL2sXitVOqtrs%3D&md5=1ba8a85d175d94d739353100f91757e0CAS | 3571232PubMed |
Garmy-Susini, B., Delmas, E., Gourdy, P., Zhou, M., Bossard, C., Bugler, B., Bayard, F., Krust, A., Prats, A. C., Doetschman, T., Prats, H., and Arnal, J. F. (2004). Role of fibroblast growth factor-2 isoforms in the effect of oestradiol on endothelial cell migration and proliferation. Circ. Res. 94, 1301–1309.
| Role of fibroblast growth factor-2 isoforms in the effect of oestradiol on endothelial cell migration and proliferation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXktFSlurw%3D&md5=0e25b29ea371cdb307fc214aa23a7abaCAS | 15073041PubMed |
Ginther, O. J. (1979). Placentation and embryology. In ‘Reproductive Biology of the Mare: Basic and Applied Aspects’. (Ed. O. J. Ginther.) pp. 308–309. (McNaughton and Gunn, Inc.: Ann Arbor, MI, USA.)
Godin, I., and Cumano, A. (2002). The hare and the tortoise: an embryonic haematopoietic race. Nat. Rev. Immunol. 2, 593–604.
| 1:CAS:528:DC%2BD38XlslGru7c%3D&md5=8419bc04377296502959ab15adb48de4CAS | 12154378PubMed |
Goldie, L. C., Nix, M. K., and Hirsch, K. K. (2008). Embryonic vasculogenesis and hematopoietic specification. Organogenesis 4, 257–263.
| Embryonic vasculogenesis and hematopoietic specification.Crossref | GoogleScholarGoogle Scholar | 19337406PubMed |
Heap, R. B., Hamon, M., and Allen, W. R. (1982). Studies on oestrogen synthesis by the preimplantation equine conceptus. J. Reprod. Fertil. Suppl. 32, 343–352.
| 1:STN:280:DyaL3s7mtl2lug%3D%3D&md5=73a08c02acbf0ee41f170803662d7be6CAS | 6962870PubMed |
Kao, Y.-C., Higashiyama, T., Sun, X., Okubo, T., Yarborough, C., Choi, I., Osawa, Y., Simmen, F. A., and Chen, S. (2000). Catalytic differences between porcine blastocyst and placental aromatase and isozymes. Eur. J. Biochem. 267, 6134–6139.
| Catalytic differences between porcine blastocyst and placental aromatase and isozymes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXnsVygsLg%3D&md5=b457818a5ab2f21f4b0f0684694b7f38CAS | 11012665PubMed |
Knospe, C. (1998). Zur Entwicklung des Pferdehodens. Anat. Histol. Embryol. 27, 219–222.
| Zur Entwicklung des Pferdehodens.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1cvhtlGktQ%3D%3D&md5=4495bb6745bb385d1bdecd92dd02bf88CAS | 9741143PubMed |
Losordo, D. W., and Isner, J. M. (2001). Oestrogen and angiogenesis: a review. Arterioscler. Thromb. Vasc. Biol. 21, 6–12.
| Oestrogen and angiogenesis: a review.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXnvFGisg%3D%3D&md5=4fd47544e264da155d11d25caa631011CAS | 11145928PubMed |
Medvinsky, A., Rybtsov, S., and Taoudi, S. (2011). Embryonic origin of the adult hematopoietic system: advances and questions. Development 138, 1017–1031.
| Embryonic origin of the adult hematopoietic system: advances and questions.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXlt1Oqt78%3D&md5=36cf3ed38aa089f71e7836dd61336cdbCAS | 21343360PubMed |
Merchant-Larios, H. (1979). Ultrastructural events in horse gonadal development. J. Reprod. Fertil. Suppl. 27, 479–485.
| 289827PubMed |
Morales, D. E., McGowan, K. A., Grant, D. S., Maheshwari, S., Bhartiya, D., Cid, M. C., Kleinman, H. K., and Schnaper, H. W. (1995). Oestrogen promotes angiogenic activity in human umbilical vein endothelial cells in vitro and in a murine model. Circulation 91, 755–763.
| 1:CAS:528:DyaK2MXktFOitLg%3D&md5=99d78436089cf21c909201383eb7397dCAS | 7530174PubMed |
Mueller, M. D., Vigne, J. L., Minchenko, A., Lebovic, D. I., Leitman, D. C., and Taylor, R. N. (2000). Regulation of vascular endothelial growth factor (VEGF) gene transcription by oestrogen receptors α and β. Proc. Natl. Acad. Sci. USA 97, 10 972–10 977.
| Regulation of vascular endothelial growth factor (VEGF) gene transcription by oestrogen receptors α and β.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXnt1ahsb0%3D&md5=509f1f0a4cbc9f9ac4521a812dc69e78CAS |
Pashen, R. L., Sheldrick, E. L., Allen, W. R., and Flint, A. P. F. (1982). Dehydroepiandrosterone synthesis by the fetal foal and its importance as an oestrogen precursor. J. Reprod. Fertil. Suppl. 32, 389–397.
| 1:STN:280:DyaL3s7mtl2ktg%3D%3D&md5=df99beef70c7e02f614522536534f45aCAS | 6220147PubMed |
Perry, J. S., Heap, R. B., and Amoroso, E. C. (1973). Early pregnancy in the pig. Nature 245, 175–188.
Pope, W. F., Maurer, R. R., and Stormshak, F. (1982). Intrauterine migration of the porcine embryo: influence of oestradiol-17β and histamine. Biol. Reprod. 27, 575–579.
| Intrauterine migration of the porcine embryo: influence of oestradiol-17β and histamine.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL38XmtVyksLY%3D&md5=d9475d0d3dbfb461543002a7cd252bd5CAS | 6814544PubMed |
Raeside, J. I. (1976). Dehydroepiandrosterone in the fetal gonads of the horse. J. Reprod. Fertil. 46, 423–425.
| Dehydroepiandrosterone in the fetal gonads of the horse.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE28Xhs1ags7c%3D&md5=7cab42288761d36c358b2ec0c9291031CAS | 130484PubMed |
Raeside, J. I., and Christie, H. L. (2008). The presence of 19-norandrostenedione and its sulphate form in yolk-sac fluid of the early equine conceptus. J. Steroid Biochem. Mol. Biol. 108, 149–154.
| The presence of 19-norandrostenedione and its sulphate form in yolk-sac fluid of the early equine conceptus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhsFyntr8%3D&md5=f55ecc1173384f5f342bae7e4f05549eCAS | 17980578PubMed |
Raeside, J. I., and Liptrap, R. L. (1975). Patterns of urinary oestrogen excretion in individual mares. J. Reprod. Fertil. Suppl. 23, 469–475.
| 1:CAS:528:DyaE28XktFeqsA%3D%3D&md5=cc1cb0046db86de6350dd81bcf4f2722CAS |
Raeside, J. I., Liptrap, R. M., McDonell, W. N., and Milne, F. J. (1979). A precursor role of DHA in a feto–placental unit for oestrogen formation in the mare. J. Reprod. Fertil. Suppl. 27, 493–497.
| 158087PubMed |
Raeside, J. I., Gofton, N., Liptrap, R. M., and Milne, F. J. (1982). Isolation and identification of steroids from gonadal vein blood of the fetal horse. J. Reprod. Fertil. Suppl. 32, 383–387.
| 1:STN:280:DyaL3s7mtl2ksQ%3D%3D&md5=3b5c9373b62f46da3fb4a1c69255cfd4CAS | 6220146PubMed |
Raeside, J. I., Berthelon, M. C., Sanchez, P., and Saez, J. M. (1988). Stimulation of aromatase activity in immature porcine Leydig cells by fibroblast growth factor (FGF). Biochem. Biophys. Res. Commun. 151, 163–169.
| Stimulation of aromatase activity in immature porcine Leydig cells by fibroblast growth factor (FGF).Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1cXhsVekt7w%3D&md5=76e845f4954102fefd19d540256d825cCAS | 3279950PubMed |
Raeside, J. I., Renaud, R. L., and Friendship, R. M. (1989). Aromatization of 19-norandrogens by porcine Leydig cells. J. Steroid Biochem. 32, 729–735.
| Aromatization of 19-norandrogens by porcine Leydig cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1MXkslWhs7c%3D&md5=cd1e5168f3df64299ef1c76b14cca146CAS | 2739415PubMed |
Raeside, J. I., Christie, H. L., and Renaud, R. L. (1999). Androgen and oestrogen metabolism in the reproductive tract and the accessory sex glands of the domestic boar (Sus scrofa). Biol. Reprod. 61, 1242–1248.
| Androgen and oestrogen metabolism in the reproductive tract and the accessory sex glands of the domestic boar (Sus scrofa).Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXmvFertrk%3D&md5=a268df778a4876456e2598c1d684a517CAS | 10529270PubMed |
Raeside, J. I., Christie, H. L., Renaud, R. L., Waelchli, R. O., and Betteridge, K. J. (2001). Steroid concentrations in yolk-sac fluid of the mare. Biol. Reprod. Suppl. 64, 280..
Raeside, J. I., Christie, H. L., Renaud, R. L., Waelchli, R. O., and Betteridge, K. J. (2004). Oestrogen metabolism in the equine conceptus and endometrium during early pregnancy in relation to oestrogen concentrations in yolk-sac fluid. Biol. Reprod. 71, 1120–1127.
| Oestrogen metabolism in the equine conceptus and endometrium during early pregnancy in relation to oestrogen concentrations in yolk-sac fluid.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXnvVGqt7s%3D&md5=a799874889a5cf2980ddc6de88cfec7aCAS | 15163615PubMed |
Raeside, J. I., Christie, H. L., Waelchli, R. O., and Betteridge, K. J. (2009). Oestrogen metabolism by the equine embryo proper during the fourth week of pregnancy. Reproduction 138, 953–960.
| Oestrogen metabolism by the equine embryo proper during the fourth week of pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsFKlur%2FK&md5=cdde1b19d47905700ff904895be2f7abCAS | 19710203PubMed |
Savard, K. (1961). The oestrogens of the pregnant mare. Endocrinology 68, 411–416.
| The oestrogens of the pregnant mare.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaF3MXmsF2gtw%3D%3D&md5=27ae75cb06750304ee5bb80b9f52c7a2CAS | 13746869PubMed |
Shifren, J. L., Tseng, J. F., Zaloudek, C. J., Ryan, I. P., Meng, Y. G., Ferrara, N., Jaffe, R. B., and Taylor, R. N. (1996). Ovarian steroid regulation of vascular endothelial growth factor in the human endometrium: implications for angiogenesis during the menstrual cycle and in the pathogenesis of endometriosis. J. Clin. Endocrinol. Metab. 81, 3112–3118.
| Ovarian steroid regulation of vascular endothelial growth factor in the human endometrium: implications for angiogenesis during the menstrual cycle and in the pathogenesis of endometriosis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XkvFWqu7k%3D&md5=3b46107663f7c60063c5bb6ca6228669CAS | 8768883PubMed |
Walt, M. L., Stabenfeldt, G. H., Hughes, J. P., Neely, D. P., and Bradley, R. (1979). Development of the equine ovary and ovulation fossa. J. Reprod. Fertil. Suppl. 27, 471–477.
| 289826PubMed |
Walters, K. W., Corbin, C. J., Anderson, G. B., Roser, J. F., and Conley, A. J. (2000). Tissue-specific localization of cytochrome P450 aromatase in the equine embryo by in situ hybridization and immunocytochemistry. Biol. Reprod. 62, 1141–1145.
| Tissue-specific localization of cytochrome P450 aromatase in the equine embryo by in situ hybridization and immunocytochemistry.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXisl2htrg%3D&md5=b4f9c7ab90662af5ec1751d109fdc633CAS | 10775160PubMed |
Zavy, M. T., Vernon, M. W., Sharp, D. C., and Bazer, F. W. (1984). Endocrine aspects of early pregnancy in pony mares. Endocrinology 115, 214–219.
| Endocrine aspects of early pregnancy in pony mares.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2cXks1KhtbY%3D&md5=a403f23014a652d6c651f505c490facbCAS | 6734514PubMed |
Zhu, B. T., and Conney, A. H. (1998). Functional role of oestrogen metabolism in target cells: review and perspectives. Carcinogenesis 19, 1–27.
| Functional role of oestrogen metabolism in target cells: review and perspectives.Crossref | GoogleScholarGoogle Scholar | 9472688PubMed |
Zondek, B. (1930). Hormonale Schwangerschaftsreaktion aus dem Harn bei Mensch und Tier. Klin. Wochenschr. 9, 2285–2289.
| Hormonale Schwangerschaftsreaktion aus dem Harn bei Mensch und Tier.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaA3MXhs1KmsQ%3D%3D&md5=04b214d185a4dbf9004314f988db4534CAS |
