Trophoblasts are specialized cells that form the outer layer of the blastocyst in equine embryos, playing a significant role in the development of the placenta. These cells are responsible for facilitating nutrient exchange between the mare and the developing fetus and contribute to the establishment of maternal-fetal communication. Trophoblasts also participate in the production of hormones necessary for pregnancy maintenance and are involved in the modulation of the immune environment to support fetal development. This page compiles peer-reviewed research studies and scholarly articles that explore the structure, function, and biological significance of trophoblasts in equine reproduction.
Kammerer R, Ballesteros A, Bonsor D, Warren J, Williams JM, Moore T, Dveksler G.In early equine pregnancy, a highly invasive trophoblast cell subpopulation, the chorionic girdle cells, invade the endometrium and form endometrial cups (EC). These cells express classical MHC molecules, thereby stimulating a humoral and cellular immune response, resulting in a massive accumulation of maternal CD4+ and CD8+ T cells around the EC. Nevertheless, no immediate destruction of endometrial cups by maternal lymphoid cells occurs, presumably due to immune tolerance. Although the environment of EC is rich in TGFB and in FOXP3+, CD4+ T cells, the mechanisms leading to tolerance have not...
Budik S, Tschulenk W, Kummer S, Walter I, Aurich C.Live cell RNA imaging has become an important tool for studying RNA localisation, dynamics and regulation in cultured cells. Limited information is available using these methods in more complex biological systems, such as conceptuses at different developmental stages. So far most of the approaches rely on microinjection of synthetic constructs into oocytes during or before fertilisation. Recently, a new generation of RNA-specific probes has been developed, the so named SmartFlare probes (Merck Millipore). These consist of a central 15-nm gold particle with target-specific DNAs immobilised on i...
Noronha LE, Antczak DF.The horse has proven to be a distinctively informative species in the study of pregnancy immunology for several reasons. First, unique aspects of the anatomy and physiology of the equine conceptus facilitate approaches that are not possible in other model organisms, such as non-surgical recovery of early stage embryos and conceptuses and isolation of pure trophoblast cell populations. Second, pregnant mares make strong cytotoxic antibody responses to paternal major histocompatibility complex class I antigens expressed by the chorionic girdle cells, permitting detailed evaluation of the antigen...
Allen WR, Wilsher S.Constant, self induced mobility throughout the uterine lumen between days 6 and 17 after ovulation, complete envelopment by a self-secreted glycoprotein capsule between days 7 and 30 and 'injection' of specialised, gonadotrophin-secreting trophoblast cells into the maternal endometrium at days 35-37 are three unusual aspects of equine embryogenesis. The outer trophoblast layer of the allantochorion finally establishes a stable, microvillous contact with the lumenal epithelium of the endometrium around days 40-42 and placentation commences thereafter. The allantochorion elongates steadily until...
de Mestre AM, Bacon SJ, Costa CC, Leadbeater JC, Noronha LE, Stewart F, Antczak DF.The chorionic girdle of the equine conceptus is comprised of specialized trophoblast cells which, at day 36-38 of equine pregnancy, gain an invasive phenotype and invade the endometrium to form endometrial cups. Studies of equine endometrial cups remain difficult to perform because of the invasive techniques required to obtain cup tissue and because sampling requires termination of the pregnancy. In this study we developed a system to model trophoblast differentiation and trophoblast-immune interactions in vitro and in vivo. We utilized a method of culturing chorionic girdle pieces in serum-fr...
Albihn A, Waelchli RO, Samper J, Oriol JG, Croy BA, Betteridge KJ.A novel xenogeneic transplantation approach was used to determine whether it is embryonic or maternal tissue that produces the material that gives rise to the mucin-like glycoprotein of the equine embryonic capsule. Endometrial biopsy samples and conceptuses from six mares at days 13-15 after ovulation were prepared as 1 mm(3) grafts of endometrium, trophoblast and capsule for transplantation, alone or in combination, into various sites in 88 immunodeficient (severe combined immunodeficient or RAG2/gamma(c) double mutant) mice. The overall recovery rate of grafts was over 50%, reaching 100% wi...
Thway TM, Wolfe MW.Primates and equids are the only species known to express the placental glycoprotein hormone, chorionic gonadotropin (CG), a heterodimeric glycoprotein composed of an alpha subunit linked to a hormone-specific beta subunit. The regulatory mechanisms involved in the induction of equine glycoprotein alpha subunit gene expression have not been identified. Epidermal growth factor (EGF) receptor is known to transduce signals that alter a number of different cellular functions (cell proliferation, differentiation, hormone secretion, and gene regulation). In the present study, we investigated the reg...
Wooding FB, Morgan G, Fowden AL, Allen WR.The placenta is the only channel for transport of nutrients to the conceptus and the fetal nutrient demands increase exponentially to term. The 9 kDa calcium binding protein (calbindin, 9CBP) and the iron binding protein uteroferrin (UF) are proving to be reliable markers for epithelia that mediate active transcellular calcium and iron transport and the glucose transporter proteins (GT1 and GT3) for glucose transport by facilitated diffusion. Light and electron microscope immunocytochemistry have been used on perfusion fixed resin embedded material to establish the distribution of 9CBP, UF, GT...
Beckers JF, Zarrouk A, Batalha ES, Garbayo JM, Mester L, Szenci O.The two main groups of placental proteins of ruminants are discussed in this paper: chorionic somatomammotropins (placental lactogens) and pregnancy-specific (-associated) proteins. Placental lactogens belong to the prolactin and growth hormone family. They stimulate mammogenesis, fetal growth and maternal metabolism. Pregnancy-specific proteins and pregnancy-associated glycoproteins belong to the aspartic proteinase family like pepsin, cathepsin D and E. These two groups of proteins are secreted in the maternal circulation by the binucleate cells after their migration to and fusion with the u...
Microscopy research and techniqueJuly 1, 1997
Volume 38, Issue 1-2 115-124 doi: 10.1002/(SICI)1097-0029(19970701/15)38:1/2<115::AID-JEMT12>3.0.CO;2-S
Ridderstråle Y, Persson E, Dantzer V, Leiser R.The placenta has multiple functions, being the organ which provides oxygen and nutrients to the developing conceptus. In the placenta, the enzyme carbonic anhydrase (CA) may provide ions for exchange with Na+, K+, and Cl- in transepithelial movement of ions and fluid, as well as facilitating carbon dioxide diffusion. It can also be active in intermediary metabolism, such as gluconeogenesis, urea, and fatty acid synthesis. Placental material from pig, horse, cow, mink, rat, and human was therefore investigated, representing placenta types with variations in shape, internal architecture, and nat...
Klonisch T, Mathias S, Cambridge G, Hombach-Klonisch S, Ryan PL, Allen WR.In situ hybridization employing a cRNA probe derived from a 428-bp fragment of equine relaxin was used to localize relaxin mRNA, and immunocytochemistry was used to localize relaxin itself, in tissues of the placenta-endometrium interface recovered between 33 and 153 days of gestation from mares carrying intraspecific horse, interspecific mule and extraspecific donkey conceptuses. Immunocytochemical staining was also used to localize trophoblast-specific and class I major histocompatibility complex (MHC) antigens on some specimens. Relaxin mRNA and relaxin were both present in the single-cell ...
Vagnoni KE, Schram BR, Ginther OJ, Lunn DP.Equine chorionic girdle cells are a subpopulation of highly invasive trophoblast cells that attach and invade the uterine epithelium on Day 35 (Day 0 = day of ovulation). These invading chorionic girdle cells form endometrial cups that are associated with a marked local maternal leukocytic response that may result in the demise of the cups at Day 120 of pregnancy. Once endometrial cups become established in the uterine wall they do not express MHC antigens, and therefore may only be susceptible to non-MHC restricted cytotoxic cells. The susceptibility of cultured chorionic girdle cells to LAK ...
Oriol JG, Sharom FJ, Betteridge KJ.The embryonic capsule, which covers the equine blastocyst after it loses its zona pellucida, is composed of mucin-like glycoproteins. In the present study, we investigated both macroscopic and molecular changes in the capsule during development. The weight of the capsule increased from day 11-12 of pregnancy and reached a maximum at about day 18, coinciding with the time during which the conceptus migrates extensively throughout the uterus. The sialic acid content of the capsule declined markedly from about day 16, the time of conceptus 'fixation' in the uterus, which suggests a unique develop...
Roth TL, White KL, Thompson DL, Horohov DW.It has been proposed that PGE2 is an important immunosuppressant acting at the fetal-maternal interface during pregnancy. We have previously shown that horse conceptus-conditioned medium suppresses lymphocyte proliferation. This experiment was designed to determine if horse conceptus-derived immunosuppressive activity could be attributed to PGE2 production by the trophoblast tissue. Trophoblast tissue from 21-day-old conceptuses was cut into equal sections and cultured in the presence or absence of the prostaglandin inhibitor, indomethacin. Following culture, immunosuppressive activity and the...
Antczak DF, Allen WR.There is little evidence for maternal immunological recognition of pregnancy in most species with the striking exception of the members of the genus Equus. Almost all mares make strong cytotoxic antibody responses to paternally inherited fetal antigens by Day 60 of gestation. Most of these responses are directed against antigens of the Major Histocompatibility Complex (MHC), which constitutes the primary immunogenetic barrier to successful organ transplantation. The source of fetal MHC antigens in the pregnant mare appears to be the specialized trophoblast cells of the chorionic girdle region ...
Antczak DF, Oriol JG, Donaldson WL, Poleman C, Stenzler L, Volsen SG, Allen WR.Monoclonal antibodies raised against horse placenta were tested using an indirect immunoperoxidase-labelling technique for reactivity with a panel of tissues from adult horses and conceptuses of various gestational ages. The pattern of reactivity of 4 of the antibodies (F67.1, F71.3, F71.7, F71.14) on trophoblastic tissues described unique antigenic phenotypes for the non-invasive trophoblast of the allantochorion, the invasive trophoblast of the chorionic girdle, and the mature endometrial cup cells, which are derived from the chorionic girdle. Two of the monoclonal antibodies (F67.1 and F71....
Allen WR.Fertilized eggs reach the uterus of the mare by the sixth day after ovulation whereas unfertilized eggs remain lodged in the fallopian tubes for many months. However, embryo removal studies indicate that the fetal message for luteal maintenance in the pregnant mare is not transmitted until Days 14-16. The equine endometrial cups comprise a series of small, ulcer-like endometrial outgrowths which are present in the pregnant horn of the uterus between 40 and 150 days of gestation. Each cup consists of a discrete colony of large, gonadotropin-secreting, trophoblast cells derived from a specialize...
Samuel CA, Allen WR, Steven DH.Microcotyledons, which are a distinctive feature of the mature equine placenta, are fully formed by Day 150 of gestation. The fetal component of each microcotyledon is developed from several primary folds of trophoblast which become elaborately subdivided as gestation proceeds. These changes are reflected in the structure of the maternal crypts, which receive the fetal villi. Between Days 60 and 150 of gestation the maternal epithelium is greatly reduced in height. No such change occurs on the fetal side of the placenta, but between Days 100 and 250 a progressive indentation of the epithelium ...
Noronha LE, Antczak DF.The horse has proven to be a distinctively informative species in the study of pregnancy immunology for several reasons. First, unique aspects of the anatomy and physiology of the equine conceptus facilitate approaches that are not possible in other model organisms, such as non-surgical recovery of early stage embryos and conceptuses and isolation of pure trophoblast cell populations. Second, pregnant mares make strong cytotoxic antibody responses to paternal major histocompatibility complex class I antigens expressed by the chorionic girdle cells, permitting detailed evaluation of the antigen...
Allen WR, Wilsher S.Constant, self induced mobility throughout the uterine lumen between days 6 and 17 after ovulation, complete envelopment by a self-secreted glycoprotein capsule between days 7 and 30 and 'injection' of specialised, gonadotrophin-secreting trophoblast cells into the maternal endometrium at days 35-37 are three unusual aspects of equine embryogenesis. The outer trophoblast layer of the allantochorion finally establishes a stable, microvillous contact with the lumenal epithelium of the endometrium around days 40-42 and placentation commences thereafter. The allantochorion elongates steadily until...
Oriol JG, Sharom FJ, Betteridge KJ.The embryonic capsule, which covers the equine blastocyst after it loses its zona pellucida, is composed of mucin-like glycoproteins. In the present study, we investigated both macroscopic and molecular changes in the capsule during development. The weight of the capsule increased from day 11-12 of pregnancy and reached a maximum at about day 18, coinciding with the time during which the conceptus migrates extensively throughout the uterus. The sialic acid content of the capsule declined markedly from about day 16, the time of conceptus 'fixation' in the uterus, which suggests a unique develop...
Kammerer R, Ballesteros A, Bonsor D, Warren J, Williams JM, Moore T, Dveksler G.In early equine pregnancy, a highly invasive trophoblast cell subpopulation, the chorionic girdle cells, invade the endometrium and form endometrial cups (EC). These cells express classical MHC molecules, thereby stimulating a humoral and cellular immune response, resulting in a massive accumulation of maternal CD4+ and CD8+ T cells around the EC. Nevertheless, no immediate destruction of endometrial cups by maternal lymphoid cells occurs, presumably due to immune tolerance. Although the environment of EC is rich in TGFB and in FOXP3+, CD4+ T cells, the mechanisms leading to tolerance have not...
Albihn A, Waelchli RO, Samper J, Oriol JG, Croy BA, Betteridge KJ.A novel xenogeneic transplantation approach was used to determine whether it is embryonic or maternal tissue that produces the material that gives rise to the mucin-like glycoprotein of the equine embryonic capsule. Endometrial biopsy samples and conceptuses from six mares at days 13-15 after ovulation were prepared as 1 mm(3) grafts of endometrium, trophoblast and capsule for transplantation, alone or in combination, into various sites in 88 immunodeficient (severe combined immunodeficient or RAG2/gamma(c) double mutant) mice. The overall recovery rate of grafts was over 50%, reaching 100% wi...
Antczak DF, Oriol JG, Donaldson WL, Poleman C, Stenzler L, Volsen SG, Allen WR.Monoclonal antibodies raised against horse placenta were tested using an indirect immunoperoxidase-labelling technique for reactivity with a panel of tissues from adult horses and conceptuses of various gestational ages. The pattern of reactivity of 4 of the antibodies (F67.1, F71.3, F71.7, F71.14) on trophoblastic tissues described unique antigenic phenotypes for the non-invasive trophoblast of the allantochorion, the invasive trophoblast of the chorionic girdle, and the mature endometrial cup cells, which are derived from the chorionic girdle. Two of the monoclonal antibodies (F67.1 and F71....
Beckers JF, Zarrouk A, Batalha ES, Garbayo JM, Mester L, Szenci O.The two main groups of placental proteins of ruminants are discussed in this paper: chorionic somatomammotropins (placental lactogens) and pregnancy-specific (-associated) proteins. Placental lactogens belong to the prolactin and growth hormone family. They stimulate mammogenesis, fetal growth and maternal metabolism. Pregnancy-specific proteins and pregnancy-associated glycoproteins belong to the aspartic proteinase family like pepsin, cathepsin D and E. These two groups of proteins are secreted in the maternal circulation by the binucleate cells after their migration to and fusion with the u...
Microscopy research and techniqueJuly 1, 1997
Volume 38, Issue 1-2 115-124 doi: 10.1002/(SICI)1097-0029(19970701/15)38:1/2<115::AID-JEMT12>3.0.CO;2-S
Ridderstråle Y, Persson E, Dantzer V, Leiser R.The placenta has multiple functions, being the organ which provides oxygen and nutrients to the developing conceptus. In the placenta, the enzyme carbonic anhydrase (CA) may provide ions for exchange with Na+, K+, and Cl- in transepithelial movement of ions and fluid, as well as facilitating carbon dioxide diffusion. It can also be active in intermediary metabolism, such as gluconeogenesis, urea, and fatty acid synthesis. Placental material from pig, horse, cow, mink, rat, and human was therefore investigated, representing placenta types with variations in shape, internal architecture, and nat...
Wooding FB, Morgan G, Fowden AL, Allen WR.The placenta is the only channel for transport of nutrients to the conceptus and the fetal nutrient demands increase exponentially to term. The 9 kDa calcium binding protein (calbindin, 9CBP) and the iron binding protein uteroferrin (UF) are proving to be reliable markers for epithelia that mediate active transcellular calcium and iron transport and the glucose transporter proteins (GT1 and GT3) for glucose transport by facilitated diffusion. Light and electron microscope immunocytochemistry have been used on perfusion fixed resin embedded material to establish the distribution of 9CBP, UF, GT...
Allen WR.Fertilized eggs reach the uterus of the mare by the sixth day after ovulation whereas unfertilized eggs remain lodged in the fallopian tubes for many months. However, embryo removal studies indicate that the fetal message for luteal maintenance in the pregnant mare is not transmitted until Days 14-16. The equine endometrial cups comprise a series of small, ulcer-like endometrial outgrowths which are present in the pregnant horn of the uterus between 40 and 150 days of gestation. Each cup consists of a discrete colony of large, gonadotropin-secreting, trophoblast cells derived from a specialize...
Vagnoni KE, Schram BR, Ginther OJ, Lunn DP.Equine chorionic girdle cells are a subpopulation of highly invasive trophoblast cells that attach and invade the uterine epithelium on Day 35 (Day 0 = day of ovulation). These invading chorionic girdle cells form endometrial cups that are associated with a marked local maternal leukocytic response that may result in the demise of the cups at Day 120 of pregnancy. Once endometrial cups become established in the uterine wall they do not express MHC antigens, and therefore may only be susceptible to non-MHC restricted cytotoxic cells. The susceptibility of cultured chorionic girdle cells to LAK ...
Klonisch T, Mathias S, Cambridge G, Hombach-Klonisch S, Ryan PL, Allen WR.In situ hybridization employing a cRNA probe derived from a 428-bp fragment of equine relaxin was used to localize relaxin mRNA, and immunocytochemistry was used to localize relaxin itself, in tissues of the placenta-endometrium interface recovered between 33 and 153 days of gestation from mares carrying intraspecific horse, interspecific mule and extraspecific donkey conceptuses. Immunocytochemical staining was also used to localize trophoblast-specific and class I major histocompatibility complex (MHC) antigens on some specimens. Relaxin mRNA and relaxin were both present in the single-cell ...
Samuel CA, Allen WR, Steven DH.Microcotyledons, which are a distinctive feature of the mature equine placenta, are fully formed by Day 150 of gestation. The fetal component of each microcotyledon is developed from several primary folds of trophoblast which become elaborately subdivided as gestation proceeds. These changes are reflected in the structure of the maternal crypts, which receive the fetal villi. Between Days 60 and 150 of gestation the maternal epithelium is greatly reduced in height. No such change occurs on the fetal side of the placenta, but between Days 100 and 250 a progressive indentation of the epithelium ...
Thway TM, Wolfe MW.Primates and equids are the only species known to express the placental glycoprotein hormone, chorionic gonadotropin (CG), a heterodimeric glycoprotein composed of an alpha subunit linked to a hormone-specific beta subunit. The regulatory mechanisms involved in the induction of equine glycoprotein alpha subunit gene expression have not been identified. Epidermal growth factor (EGF) receptor is known to transduce signals that alter a number of different cellular functions (cell proliferation, differentiation, hormone secretion, and gene regulation). In the present study, we investigated the reg...
Antczak DF, Allen WR.There is little evidence for maternal immunological recognition of pregnancy in most species with the striking exception of the members of the genus Equus. Almost all mares make strong cytotoxic antibody responses to paternally inherited fetal antigens by Day 60 of gestation. Most of these responses are directed against antigens of the Major Histocompatibility Complex (MHC), which constitutes the primary immunogenetic barrier to successful organ transplantation. The source of fetal MHC antigens in the pregnant mare appears to be the specialized trophoblast cells of the chorionic girdle region ...
de Mestre AM, Bacon SJ, Costa CC, Leadbeater JC, Noronha LE, Stewart F, Antczak DF.The chorionic girdle of the equine conceptus is comprised of specialized trophoblast cells which, at day 36-38 of equine pregnancy, gain an invasive phenotype and invade the endometrium to form endometrial cups. Studies of equine endometrial cups remain difficult to perform because of the invasive techniques required to obtain cup tissue and because sampling requires termination of the pregnancy. In this study we developed a system to model trophoblast differentiation and trophoblast-immune interactions in vitro and in vivo. We utilized a method of culturing chorionic girdle pieces in serum-fr...
Roth TL, White KL, Thompson DL, Horohov DW.It has been proposed that PGE2 is an important immunosuppressant acting at the fetal-maternal interface during pregnancy. We have previously shown that horse conceptus-conditioned medium suppresses lymphocyte proliferation. This experiment was designed to determine if horse conceptus-derived immunosuppressive activity could be attributed to PGE2 production by the trophoblast tissue. Trophoblast tissue from 21-day-old conceptuses was cut into equal sections and cultured in the presence or absence of the prostaglandin inhibitor, indomethacin. Following culture, immunosuppressive activity and the...
Budik S, Tschulenk W, Kummer S, Walter I, Aurich C.Live cell RNA imaging has become an important tool for studying RNA localisation, dynamics and regulation in cultured cells. Limited information is available using these methods in more complex biological systems, such as conceptuses at different developmental stages. So far most of the approaches rely on microinjection of synthetic constructs into oocytes during or before fertilisation. Recently, a new generation of RNA-specific probes has been developed, the so named SmartFlare probes (Merck Millipore). These consist of a central 15-nm gold particle with target-specific DNAs immobilised on i...
