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Vertebrate reproductive science and technology
REVIEW

Understanding placentation in ruminants: a review focusing on cows and sheep

Gregory A. Johnson https://orcid.org/0000-0003-1949-1797 A * , Fuller W. Bazer B , Heewon Seo A , Robert C. Burghardt A , Guoyao Wu B , Ky G. Pohler https://orcid.org/0000-0003-2429-0893 B and Joe W. Cain A
+ Author Affiliations
- Author Affiliations

A Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA.

B Department of Animal Science, Texas A&M University, College Station, TX 77843, USA.

* Correspondence to: gjohnson@cvm.tamu.edu

Reproduction, Fertility and Development 36(2) 93-111 https://doi.org/10.1071/RD23119

© 2024 The Author(s) (or their employer(s)). Published by CSIRO Publishing on behalf of the IETS

Abstract

Mammals differ regarding their placentae, but in all species placental trophoblasts interact intimately with the uterine endometrium to mediate the transfer of nutrients from the mother to the embryo/fetus through the closely juxtaposed microcirculatory systems of the uterus and placenta. Placentation in ruminants is intermediate between the non-invasive type, as observed in the epitheliochorial placenta of pigs, and the invasive type, as observed in the haemochorial placentae of mice and humans. In ruminants, placental trophoblast cells invade uterine endometrial tissue, but invasion is believed to be limited to the endometrial luminal epithelium (LE). In the LE there are varying degrees of syncytialisation among species, with syncytialisation being more extensive in sheep than cows. The hallmarks of placentation in ruminants include: (1) an extended period in which conceptuses (embryos and associated placental membranes) elongate and must be supported by secretions (histotroph) from the uterus; (2) a cascade involving an array of adhesion molecules that includes integrin-mediated attachment of the conceptus trophoblast to the endometrial LE for implantation; (3) syncytialisation of the developing early placenta, a process for which there is currently limited understanding; and (4) development of placentomes that define the cotyledonary placentae of cows and sheep, and provide haemotrophic support of fetal development.

Keywords: conceptus elongation, conceptus implantation, cows, endometrium, placentation, placentomes, pregnancy, sheep, syncytialisation, trophoblast.

References

Albelda SM, Buck CA (1990) Integrins and other cell adhesion molecules. The FASEB Journal 4, 2868-2880.
| Crossref | Google Scholar | PubMed |

Aplin JD, Kimber SJ (2004) Trophoblast-uterine interactions at implantation. Reproductive Biology and Endocrinology 2, 48-60.
| Crossref | Google Scholar | PubMed |

Aplin JD, Meseguer M, Simon C, Ortiz ME, Croxatto H, Jones CJP (2001) MUC1, glycans and the cell-surface barrier to embryo implantation. Biochemical Society Transactions 29, 153-156.
| Crossref | Google Scholar | PubMed |

Assis Neto AC, Pereira FTV, Santos TC, Ambrosio CE, Leiser R, Miglino MA (2010) Morpho-physical recording of bovine conceptus (Bos indicus) and placenta from days 20 to 70 of pregnancy. Reproduction in Domestic Animals 45, 760-772.
| Crossref | Google Scholar | PubMed |

Bauersachs S, Wolf E (2015) Uterine responses to the preattachment embryo in domestic ungulates: recognition of pregnancy and preparation for implantation. Annual Review of Animal Biosciences 3, 489-511.
| Crossref | Google Scholar | PubMed |

Bauersachs S, Ulbrich SE, Reichenbach H-D, Reichenbach M, Büttner M, Meyer HHD, Spencer TE, Minten M, Sax G, Winter G, Wolf E (2012) Comparison of the effects of early pregnancy with human interferon, alpha 2 (IFNA2), on gene expression in bovine endometrium. Biology of Reproduction 86, 46.
| Crossref | Google Scholar | PubMed |

Bazer FW, Thatcher WW (2017) Chronicling the discovery of interferon tau. Reproduction 154, F11-F20.
| Crossref | Google Scholar | PubMed |

Bazer FW, Johnson GA, Spencer TE (2005) Growth and development: pre-implantation embryo. In ‘Encyclopedia of animal science, Vol. 1’. (Eds WG Pond, AW Bell) pp. 1–3. (Marcel Dekker)

Bazer FW, Wu G, Spencer TE, Johnson GA, Burghardt RC, Bayless K (2010) Novel pathways for implantation and establishment and maintenance of pregnancy in mammals. Molecular Human Reproduction 16, 135-152.
| Crossref | Google Scholar | PubMed |

Bazer FW, Wu G, Johnson GA, Kim J, Song G (2011) Uterine histotroph and conceptus development: select nutrients and secreted phosphoprotein 1 affect mechanistic target of rapamycin cell signaling in ewes. Biology of Reproduction 85, 1094-1107.
| Crossref | Google Scholar | PubMed |

Bazer FW, Song G, Kim J, Erikson DW, Johnson GA, Burghardt RC, Gao H, Carey Satterfield M, Spencer TE, Wu G (2012) Mechanistic mammalian target of rapamycin (MTOR) cell signaling: effects of select nutrients and secreted phosphoprotein 1 on development of mammalian conceptuses. Molecular and Cellular Endocrinology 354, 22-33.
| Crossref | Google Scholar | PubMed |

Bazer FW, Wang X, Johnson GA, Wu G (2015) Select nutrients and their effects on conceptus development in mammals. Animal Nutrition 1, 85-95.
| Crossref | Google Scholar | PubMed |

Bazer FW, Burghardt RC, Johnson GA, Spencer TE, Wu G (2018) Mechanisms for the establishment and maintenance of pregnancy: synergies from scientific collaborations. Biology of Reproduction 99, 225-241.
| Crossref | Google Scholar | PubMed |

Bazer FW, Seo H, Wu G, Johnson GA (2020) Interferon tau: influences on growth and development of the conceptus. Theriogenology 150, 75-83.
| Crossref | Google Scholar | PubMed |

Beltman ME, Lonergan P, Diskin MG, Roche JF, Crowe MA (2009) Effect of progesterone supplementation in the first week post conception on embryo survival in beef heifers. Theriogenology 71, 1173-1179.
| Crossref | Google Scholar | PubMed |

Betteridge KJ, Fléchon J-E (1988) The anatomy and physiology of the pre-attachment bovine embryos. Theriogenology 29, 155-187.
| Crossref | Google Scholar |

Betteridge KJ, Eaglesome MD, Randall GCB, Mitchell D (1980) Collection, description and transfer of embryos from cattle 10-16 days after oestrus. Journal of Reproduction and Fertility 59, 205-216.
| Crossref | Google Scholar | PubMed |

Black SG, Arnaud F, Palmarini M, Spencer TE (2010) Endogenous retroviruses in trophoblast differentiation and placental development. American Journal of Reproductive Immunology 64, 255-264.
| Crossref | Google Scholar | PubMed |

Blaise S, de Parseval N, Bénit L, Heidmann T (2003) Genomewide screening for fusogenic human endogenous retrovirus envelopes identifies syncytin 2, a gene conserved on primate evolution. Proceedings of the National Academy of Sciences of the United States of America 100, 13013-13018.
| Crossref | Google Scholar | PubMed |

Blond J-L, Lavillette D, Cheynet V, Bouton O, Oriol G, Chapel-Fernandes S, Mandrand B, Mallet F, Cosset F-L (2000) An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor. Journal of Virology 74, 3321-3329.
| Crossref | Google Scholar | PubMed |

Bowen JA, Bazer FW, Burghardt RC (1996) Spatial and temporal analyses of integrin and Muc-1 expression in porcine uterine epithelium and trophectoderm in vivo. Biology of Reproduction 55, 1098-1106.
| Crossref | Google Scholar | PubMed |

Bridger PS, Haupt S, Klisch K, Leiser R, Tinneberg H-R, Pfarrer C (2007a) Validation of primary epitheloid cell cultures isolated from bovine placental caruncles and cotyledons. Theriogenology 68, 592-603.
| Crossref | Google Scholar | PubMed |

Bridger PS, Menge C, Leiser R, Tinneberg H-R, Pfarrer CD (2007b) Bovine caruncular epithelial cell line (BCEC-1) isolated from the placenta forms a functional epithelial barrier in a polarized cell culture model. Placenta 28, 1110-1117.
| Crossref | Google Scholar | PubMed |

Bridger PS, Haupt S, Leiser R, Johnson GA, Burghardt RC, Tinneberg H-R, Pfarrer C (2008) Integrin activation in bovine placentomes and in caruncular epithelial cells isolated from pregnant cows. Biology of Reproduction 79, 274-282.
| Crossref | Google Scholar | PubMed |

Brooks K, Burns G, Spencer TE (2014) Conceptus elongation in ruminants: roles of progesterone, prostaglandin, interferon tau and cortisol. Journal of Animal Science and Biotechnology 5, 53.
| Crossref | Google Scholar |

Brown K, Heller DS, Zamudio S, Illsley NP (2011) Glucose transporter 3 (GLUT3) protein expression in human placenta across gestation. Placenta 32, 1041-1049.
| Crossref | Google Scholar | PubMed |

Burghardt RC, Johnson GA, Jaeger LA, Ka H, Garlow JE, Spencer TE, Bazer FW (2002) Integrins and extracellular matrix proteins at the maternal/fetal interface in domestic animals. Cells Tissues Organs 172, 202-217.
| Crossref | Google Scholar | PubMed |

Burton GJ, Jauniaux E, Murray AJ (2017) Oxygen and placental development; parallels and differences with tumour biology. Placenta 56, 14-18.
| Crossref | Google Scholar | PubMed |

Burton GJ (2022) Placental types. In ‘Benirschke’s pathology of the human placenta’. (Eds RN Baergen, GJ Burton, CG Kaplan) pp. 23–38. (Springer) doi:10.1007/978-3-030-84725-8_4

Camolotto S, Racca A, Rena V, Nores R, Patrito LC, Genti-Raimondi S, Panzetta-Dutari GM (2010) Expression and transcriptional regulation of individual pregnancy-specific glycoprotein genes in differentiating trophoblast cells. Placenta 31, 312-319.
| Crossref | Google Scholar | PubMed |

Carter F, Forde N, Duffy P, Wade M, Fair T, Crowe MA, Evans ACO, Kenny DA, Roche JF, Lonergan P (2008) Effect of increasing progesterone concentration from day 3 of pregnancy on subsequent embryo survival and development in beef heifers. Reproduction, Fertility and Development 20, 368-375.
| Crossref | Google Scholar | PubMed |

Charpigny G, Reinaud P, Tamby J-P, Créminon C, Guillomot M (1997a) Cyclooxygenase-2 unlike cyclooxygenase-1 is highly expressed in ovine embryos during the implantation period. Biology of Reproduction 57, 1032-1040.
| Crossref | Google Scholar | PubMed |

Charpigny G, Reinaud P, Tamby J-P, Créminon C, Martal J, Maclouf J, Guillomot M (1997b) Expression of cyclooxygenase-1 and -2 in ovine endometrium during the estrous cycle and early pregnancy. Endocrinology 138, 2163-2171.
| Crossref | Google Scholar | PubMed |

Clemente M, de La Fuente J, Fair T, Al Naib A, Gutierrez-Adan A, Roche JF, Rizos D, Lonergan P (2009) Progesterone and conceptus elongation in cattle: a direct effect on the embryo or an indirect effect via the endometrium? Reproduction 138, 507-517.
| Crossref | Google Scholar | PubMed |

Cross JC, Baczyk D, Dobric N, Hemberger M, Hughes M, Simmons DG, Yamamoto H, Kingdom JCP (2003) Genes, development and evolution of the placenta. Placenta 24, 123-130.
| Crossref | Google Scholar | PubMed |

Davenport KM, Ortega MS, Liu H, O’Neil EV, Kelleher AM, Warren WC, Spencer TE (2023) Single-nuclei RNA sequencing (snRNA-seq) uncovers trophoblast cell types and lineages in the mature bovine placenta. Proceedings of the National Academy of Sciences of the United States of America 120, e2221526120.
| Crossref | Google Scholar |

De Bem THC, Tinning H, Vasconcelos EJR, Wang D, Forde N (2021) Endometrium on-a-chip reveals insulin- and glucose-induced alterations in the transcriptome and proteomic secretome. Endocrinology 162, bqab054.
| Crossref | Google Scholar |

Dorniak P, Bazer FW, Spencer TE (2011) Prostaglandins regulate conceptus elongation and mediate effects of interferon tau on the ovine uterine endometrium. Biology of Reproduction 84, 1119-1127.
| Crossref | Google Scholar | PubMed |

Dorniak P, Bazer FW, Wu G, Spencer TE (2012) Conceptus-derived prostaglandins regulate endometrial function in sheep. Biology of Reproduction 87, 1-7.
| Crossref | Google Scholar | PubMed |

Dorniak P, Welsh TH, Jr, Bazer FW, Spencer TE (2013) Cortisol and interferon tau regulation of endometrial function and conceptus development in female sheep. Endocrinology 154, 931-941.
| Crossref | Google Scholar | PubMed |

Duello TM, Byatt JC, Bremel RD (1986) Immunohistochemical localization of placental lactogen in binucleate cells of bovine placentomes. Endocrinology 119, 1351-1355.
| Crossref | Google Scholar | PubMed |

Dunlap KA, Palmarini M, Spencer TE (2006) Ovine endogenous betaretroviruses (enJSRVs) and placental morphogenesis. Placenta 27(Suppl), 135-140.
| Crossref | Google Scholar |

Dunlap KA, White BG, Erikson DW, Satterfield MC, Pfarrer C, Wu G, Bazer FW, Burghardt RC, Bayless KJ, Johnson GA (2020) FTY720, a sphingosine analog, altered placentome histoarchitecture in ewes. Journal of Animal Science and Biotechnology 11, 2.
| Crossref | Google Scholar |

Dupressoir A, Marceau G, Vernochet C, Bénit L, Kanellopoulos C, Sapin V, Heidmann T (2005) Syncytin-A and syncytin-B, two fusogenic placenta-specific murine envelope genes of retroviral origin conserved in Muridae. Proceedings of the National Academy of Sciences of the United States of America 102, 725-730.
| Crossref | Google Scholar | PubMed |

Edwards AK, McKnight SM, Askelson K, McKnight JR, Dunlap KA, Satterfield MC (2020) Adaptive responses to maternal nutrient restriction alter placental transport in ewes. Placenta 96, 1-9.
| Crossref | Google Scholar | PubMed |

Farin CE, Imakawa K, Roberts RM (1989) In situ localization of mRNA for the interferon, ovine trophoblast protein-1, during early embryonic development of the sheep. Molecular Endocrinology 3, 1099-1107.
| Crossref | Google Scholar | PubMed |

Ferrell CL, Ford SP, Prior RL, Christenson RK (1983) Blood flow, steroid secretion and nutrient uptake of the gravid bovine uterus and fetus. Journal of Animal Science 56, 656-667.
| Crossref | Google Scholar | PubMed |

Fleming J-AGW, Choi Y, Johnson GA, Spencer TE, Bazer FW (2001) Cloning of the ovine estrogen receptor-α promoter and functional regulation by ovine interferon-τ. Endocrinology 142, 2879-2887.
| Crossref | Google Scholar | PubMed |

Forde N, Lonergan P (2012) Transcriptomic analysis of the bovine endometrium: what is required to establish uterine receptivity to implantation in cattle? Journal of Reproduction and Development 58, 189-195.
| Crossref | Google Scholar | PubMed |

Forde N, Carter F, Fair T, Crowe MA, Evans ACO, Spencer TE, Bazer FW, McBride R, Boland MP, O’Gaora P, Lonergan P, Roche JF (2009) Progesterone-regulated changes in endometrial gene expression contribute to advanced conceptus development in cattle. Biology of Reproduction 81, 784-794.
| Crossref | Google Scholar | PubMed |

Forde N, Beltman ME, Duffy GB, Duffy P, Mehta JP, O’Gaora P, Roche JF, Lonergan P, Crowe MA (2011a) Changes in the endometrial transcriptome during the bovine estrous cycle: effect of low circulating progesterone and consequences for conceptus elongation. Biology of Reproduction 84, 266-278.
| Crossref | Google Scholar | PubMed |

Forde N, Carter F, Spencer TE, Bazer FW, Sandra O, Mansouri-Attia N, Okumu LA, McGettigan PA, Mehta JP, McBride R, O’Gaora P, Roche JF, Lonergan P (2011b) Conceptus-induced changes in the endometrial transcriptome: how soon does the cow know she is pregnant? Biology of Reproduction 85, 144-156.
| Crossref | Google Scholar | PubMed |

Forde N, Mehta JP, Minten M, Crowe MA, Roche JF, Spencer TE, Lonergan P (2012) Effects of low progesterone on the endometrial transcriptome in cattle. Biology of Reproduction 87, 124.
| Crossref | Google Scholar | PubMed |

Forde N, McGettigan PA, Mehta JP, O’Hara L, Mamo S, Bazer FW, Spencer TE, Lonergan P (2014) Proteomic analysis of uterine fluid during the pre-implantation period of pregnancy in cattle. Reproduction 147, 575-587.
| Crossref | Google Scholar | PubMed |

Frank JW, Steinhauser CB, Wang X, Burghardt RC, Bazer FW, Johnson GA (2021) Loss of ITGB3 in ovine conceptuses decreases conceptus expression of NOS3 and SPP1: implications for the developing placental vasculature. Biology of Reproduction 104, 657-668.
| Crossref | Google Scholar | PubMed |

Frendo J-L, Olivier D, Cheynet V, Blond J-L, Bouton O, Vidaud M, Rabreau M, Evain-Brion D, Mallet F (2003) Direct involvement of HERV-W Env glycoprotein in human trophoblast cell fusion and differentiation. Molecular and Cellular Biology 23, 3566-3574.
| Crossref | Google Scholar | PubMed |

Gao H, Wu G, Spencer TE, Johnson GA, Li X, Bazer FW (2009a) Select nutrients in the ovine uterine lumen. I. Amino acids, glucose, and ions in uterine lumenal flushings of cyclic and pregnant ewes. Biology of Reproduction 80, 86-93.
| Crossref | Google Scholar | PubMed |

Gao H, Wu G, Spencer TE, Johnson GA, Bazer FW (2009b) Select nutrients in the ovine uterine lumen. II. Glucose transporters in the uterus and peri-implantation conceptuses. Biology of Reproduction 80, 94-104.
| Crossref | Google Scholar | PubMed |

Gao H, Wu G, Spencer TE, Johnson GA, Bazer FW (2009c) Select nutrients in the ovine uterine lumen. III. Cationic amino acid transporters in the ovine uterus and peri-implantation conceptuses. Biology of Reproduction 80, 602-609.
| Crossref | Google Scholar | PubMed |

Gao H, Wu G, Spencer TE, Johnson GA, Bazer FW (2009d) Select nutrients in the ovine uterine lumen. IV. Expression of neutral and acidic amino acid transporters in ovine uteri and peri-implantation conceptuses. Biology of Reproduction 80, 1196-1208.
| Crossref | Google Scholar | PubMed |

Garrett JE, Geisert RD, Zavy MT, Morgan GL (1988) Evidence for maternal regulation of early conceptus growth and development in beef cattle. Journal of Reproduction and Fertility 84, 437-446.
| Crossref | Google Scholar | PubMed |

Giancotti FG, Ruoslahti E (1999) Integrin signaling. Science 285, 1028-1033.
| Crossref | Google Scholar | PubMed |

Godkin JD, Bazer FW, Thatcher WW, Roberts RM (1984) Proteins released by cultured day 15–16 conceptuses prolong luteal maintenance when introduced into the uterine lumen of cyclic ewes. Journal of Reproduction and Fertility 71, 57-64.
| Crossref | Google Scholar | PubMed |

Goodwin RFW (1956) Division of the common mammals into two groups according to the concentration of fructose in the blood of the foetus. The Journal of Physiology 132, 146-156.
| Crossref | Google Scholar | PubMed |

Gray CA, Adelson DL, Bazer FW, Burghardt RC, Meeusen ENT, Spencer TE (2004) Discovery and characterization of an epithelial-specific galectin in the endometrium that forms crystals in the trophectoderm. Proceedings of the National Academy of Sciences 101, 7982-7987.
| Crossref | Google Scholar | PubMed |

Grazul-Bilska AT, Borowicz PP, Johnson ML, Minten MA, Bilski JJ, Wroblewski R, Redmer DA, Reynolds LP (2010) Placental development during early pregnancy in sheep: vascular growth and expression of angiogenic factors in maternal placenta. Reproduction 140, 165-174.
| Crossref | Google Scholar | PubMed |

Green JA, Geisert RD, Johnson GA, Spencer TE (2021) Implantation and placentation in ruminants. In ‘Placentation in mammals, Vol. 234’. Advances in Anatomy, Embryology and Cell Biology. (Eds RD Geisert, T Spencer) pp. 129–154. (Springer)

Grosser O (1909) ‘Vergleichende Anatomie und Entwicklungsgeschichte der Eihaute und der Placenta.’ (W. Braumuller: Vienna and Leipzig)

Grosser O (1927) ‘Fruhentwicklung, Eihautbidung und Placentation des Menschen und der Saugetiere.’ (J. F. Bergmann: Munchen)

Guillomot M, Guay P (1982) Ultrastructural features of the cell surfaces of uterine and trophoblastic epithelia during embryo attachment in the cow. The Anatomical Record 204, 315-322.
| Crossref | Google Scholar | PubMed |

Guillomot M, Fléchon J-E, Wintenberger-Torres S (1981) Conceptus attachment in the ewe: an ultrastructural study. Placenta 2, 169-181.
| Crossref | Google Scholar | PubMed |

Guillomot M, Michel C, Gaye P, Charlier N, Trojan J, Martal J (1990) Cellular localization of an embryonic interferon, ovine trophoblastin and its mRNA in sheep embryos during early pregnancy. Biology of the Cell 68, 205-211.
| Crossref | Google Scholar | PubMed |

Haeger J-D, Hambruch N, Dilly M, Froehlich R, Pfarrer C (2011) Formation of bovine placental trophoblast spheroids. Cells Tissues Organs 193, 274-284.
| Crossref | Google Scholar | PubMed |

Haeger J-D, Hambruch N, Dantzer V, Hoelker M, Schellander K, Klisch K, Pfarrer C (2015) Changes in endometrial ezrin and cytokeratin 18 expression during bovine implantation and in caruncular endometrial spheroids in vitro. Placenta 36, 821-831.
| Crossref | Google Scholar | PubMed |

Haeger J-D, Hambruch N, Pfarrer C (2016) The bovine placenta in vivo and in vitro. Theriogenology 86, 306-312.
| Crossref | Google Scholar | PubMed |

Halloran KM, Stenhouse C, Moses RM, Kramer AC, Sah N, Seo H, Lamarre SG, Johnson GA, Wu G, Bazer FW (2023) The ovine conceptus utilizes extracellular serine, glucose, and fructose to generate formate via the one carbon metabolism pathway. Amino Acids 55, 125-137.
| Crossref | Google Scholar | PubMed |

Hill JR, Burghardt RC, Jones K, Long CR, Looney CR, Shin T, Spencer TE, Thompson JA, Winger QA, Westhusin ME (2000) Evidence for placental abnormality as the major cause of mortality in first-trimester somatic cell cloned bovine fetuses. Biology of Reproduction 63, 1787-1794.
| Crossref | Google Scholar | PubMed |

Hoffman LH, Wooding FBP (1993) Giant and binucleate trophoblast cells of mammals. Journal of Experimental Zoology 266, 559-577.
| Crossref | Google Scholar | PubMed |

Hradecký P, Mossman HW, Stott GG (1988) Comparative development of ruminant placentomes. Theriogenology 29, 715-729.
| Crossref | Google Scholar | PubMed |

Humphries JD, Byron A, Humphries MJ (2006) Integrin ligands at a glance. Journal of Cell Science 119, 3901-3903.
| Crossref | Google Scholar | PubMed |

Humphries JD, Chastney MR, Askari JA, Humphries MJ (2019) Signal transduction via integrin adhesion complexes. Current Opinion in Cell Biology 56, 14-21.
| Crossref | Google Scholar | PubMed |

Hynes RO (1987) Integrins: a family of cell surface receptors. Cell 48, 549-554.
| Crossref | Google Scholar | PubMed |

Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110, 673-687.
| Crossref | Google Scholar | PubMed |

Jansson T, Wennergren M, Illsley NP (1993) Glucose transporter protein expression in human placenta throughout gestation and in intrauterine growth retardation. The Journal of Clinical Endocrinology and Metabolism 77, 1554-1562.
| Crossref | Google Scholar | PubMed |

Jeong W, Bazer FW, Song G, Kim J (2016) Expression of hypoxia-inducible factor-1 by trophectoderm cells in response to hypoxia and epidermal growth factor. Biochemical and Biophysical Research Communications 469, 176-182.
| Crossref | Google Scholar | PubMed |

Ji L, Brkić J, Liu M, Fu G, Peng C, Wang Y-L (2013) Placental trophoblast cell differentiation: physiological regulation and pathological relevance to preeclampsia. Molecular Aspects of Medicine 34, 981-1023.
| Crossref | Google Scholar | PubMed |

Johnson GA (2018) Domestic animal placentation. In ‘Encyclopedia of reproduction, Vol. 2’. (Ed. MK Skinner) pp. 448–454. (Academic Press)

Johnson GA, Spencer TE, Burghardt RC, Bazer FW (1999a) Ovine Osteopontin: I. Cloning and expression of messenger ribonucleic acid in the uterus during the periimplantation period. Biology of Reproduction 61, 884-891.
| Crossref | Google Scholar | PubMed |

Johnson GA, Burghardt RC, Spencer TE, Newton GR, Ott TL, Bazer FW (1999b) Ovine Osteopontin: II. Osteopontin and αvβ3 integrin expression in the uterus and conceptus during the periimplantation period. Biology of Reproduction 61, 892-899.
| Crossref | Google Scholar | PubMed |

Johnson GA, Spencer TE, Burghardt RC, Taylor KM, Gray CA, Bazer FW (2000) Progesterone modulation of osteopontin gene expression in the ovine uterus. Biology of Reproduction 62, 1315-1321.
| Crossref | Google Scholar | PubMed |

Johnson GA, Bazer FW, Jaeger LA, Ka H, Garlow JE, Pfarrer C, Spencer TE, Burghardt RC (2001) Muc-1, integrin, and osteopontin expression during the implantation cascade in sheep. Biology of Reproduction 65, 820-828.
| Crossref | Google Scholar | PubMed |

Johnson GA, Burghardt RC, Bazer FW, Spencer TE (2003) Osteopontin: roles in implantation and placentation. Biology of Reproduction 69, 1458-1471.
| Crossref | Google Scholar | PubMed |

Johnson GA, Burghardt RC, Bazer FW (2014) Osteopontin: a leading candidate adhesion molecule for implantation in pigs and sheep. Journal of Animal Science and Biotechnology 5, 56.
| Crossref | Google Scholar |

Johnson GA, Bazer FW, Burghardt RC, Wu G, Seo H, Kramer AC, McLendon BA (2018) Cellular events during ovine implantation and impact for gestation. Animal Reproduction 15, 843-855.
| Crossref | Google Scholar | PubMed |

Johnson GA, Bazer FW, Seo H (2021) The early stages of implantation and placentation in the pig. In ‘Placentation in mammals, Vol. 234’. Advances in Anatomy, Embryology and Cell Biology. (Eds RD Geisert, T Spencer) pp. 61–89. (Springer)

Johnson GA, Seo H, Bazer FW, Wu G, Kramer AC, McLendon BA, Cain JW (2023) Metabolic pathways utilized by the porcine conceptus, uterus, and placenta. Molecular Reproduction & Development 90, 673-683.
| Crossref | Google Scholar | PubMed |

Karen A, Beckers J-F, Sulon J, de Sousa NM, Szabados K, Reczigel J, Szenci O (2003) Early pregnancy diagnosis in sheep by progesterone and pregnancy-associated glycoprotein tests. Theriogenology 59, 1941-1948.
| Crossref | Google Scholar | PubMed |

Kim J, Erikson DW, Burghardt RC, Spencer TE, Wu G, Bayless KJ, Johnson GA, Bazer FW (2010) Secreted phosphoprotein 1 binds integrins to initiate multiple cell signaling pathways, including FRAP1/mTOR, to support attachment and force-generated migration of trophectoderm cells. Matrix Biology 29, 369-382.
| Crossref | Google Scholar | PubMed |

Kim J-Y, Burghardt RC, Wu G, Johnson GA, Spencer TE, Bazer FW (2011a) Select nutrients in the ovine uterine lumen. VII. Effects of arginine, leucine, glutamine, and glucose on trophectoderm cell signaling, proliferation, and migration. Biology of Reproduction 84, 62-69.
| Crossref | Google Scholar | PubMed |

Kim J-Y, Burghardt RC, Wu G, Johnson GA, Spencer TE, Bazer FW (2011b) Select nutrients in the ovine uterine lumen. VIII. Arginine stimulates proliferation of ovine trophectoderm cells through mTOR-RPS6K-RPS6 signaling cascade and synthesis of nitric oxide and polyamines. Biology of Reproduction 84, 70-78.
| Crossref | Google Scholar | PubMed |

Kim J, Song G, Wu G, Bazer FW (2012) Functional roles of fructose. Proceedings of the National Academy of Sciences of the United States of America 109, E1619-E1628.
| Crossref | Google Scholar | PubMed |

King GJ, Atkinson BA, Robertson HA (1982) Implantation and early placentation in domestic ungulates. Journal of Reproduction and Fertility 31, 17-30.
| Google Scholar | PubMed |

Klisch K, Hecht W, Pfarrer C, Schuler G, Hoffmann B, Leiser R (1999) DNA content and ploidy level of bovine placentomal trophoblast giant cells. Placenta 20, 451-458.
| Crossref | Google Scholar | PubMed |

Klisch K, Thomsen PD, Dantzer V, Leiser R (2004) Genome multiplication is a generalised phenomenon in placentomal and interplacentomal trophoblast giant cells in cattle. Reproduction, Fertility and Development 16, 301-306.
| Crossref | Google Scholar | PubMed |

Kramer AC, Steinhauser CB, Gao H, Seo H, McLendon BA, Burghardt RC, Wu G, Bazer FW, Johnson GA (2020) Steroids regulate SLC2A1 and SLC2A3 to deliver glucose into trophectoderm for metabolism via glycolysis. Endocrinology 161, bqaa098.
| Crossref | Google Scholar |

Kwon H, Spencer TE, Bazer FW, Wu G (2003) Developmental changes of amino acids in ovine fetal fluids. Biology of Reproduction 68, 1813-1820.
| Crossref | Google Scholar | PubMed |

Leiser R, Krebs C, Klisch K, Ebert B, Dantzer V, Schuler G, Hoffmann B (1997) Fetal villosity and microvasculature of the bovine placentome in the second half of gestation. Journal of Anatomy 191, 517-527.
| Crossref | Google Scholar | PubMed |

Lessey BA (2002) Adhesion molecules and implantation. Journal of Reproductive Immunology 55, 101-112.
| Crossref | Google Scholar | PubMed |

Lewis SK, Farmer JL, Burghardt RC, Newton GR, Johnson GA, Adelson DL, Bazer FW, Spencer TE (2007) Galectin 15 (LGALS15): a gene uniquely expressed in the uteri of sheep and goats that functions in trophoblast attachment. Biology of Reproduction 77, 1027-1036.
| Crossref | Google Scholar | PubMed |

Lonergan P, Woods A, Fair T, Carter F, Rizos D, Ward F, Quinn K, Evans A (2007) Effect of embryo source and recipient progesterone environment on embryo development in cattle. Reproduction, Fertility and Development 19, 861-868.
| Crossref | Google Scholar |

Mallet F, Bouton O, Prudhomme S, Cheynet V, Oriol G, Bonnaud B, Lucotte G, Duret L, Mandrand B (2004) The endogenous retroviral locus ERVWE1 is a bona fide gene involved in hominoid placental physiology. Proceedings of the National Academy of Sciences of the United States of America 101, 1731-1736.
| Crossref | Google Scholar | PubMed |

McNamee EN, Korns Johnson D, Homann D, Clambey ET (2013) Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function. Immunologic Research 55, 58-70.
| Crossref | Google Scholar | PubMed |

Mellor DJ, Mitchell B, Matheson IC (1977) Reductions in lamb weight caused by pre-mating carunclectomy and mid-pregnancy placental ablation. Journal of Comparative Pathology 87, 629-633.
| Crossref | Google Scholar | PubMed |

Meznarich HK, Hay WW, Jr, Sparks JW, Meschia G, Battaglia FC (1987) Fructose disposal and oxidation rates in the ovine fetus. Quarterly Journal of Experimental Physiology 72, 617-625.
| Crossref | Google Scholar | PubMed |

Mi S, Lee X, Li X-P, Veldman GM, Finnerty H, Racie L, LaVallie E, Tang X-Y, Edouard P, Howes S, Keith JC, Jr, McCoy JM (2000) Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 403, 785-789.
| Crossref | Google Scholar | PubMed |

Moses RM, Halloran KM, Stenhouse C, Sah N, Kramer AC, McLendon BA, Seo H, Johnson GA, Wu G, Bazer FW (2022) Ovine conceptus tissue metabolizes fructose for metabolic support during the peri-implantation period of pregnancy. Biology of Reproduction 107, 1084-1096.
| Crossref | Google Scholar | PubMed |

Muniz JJ, Joyce MM, Taylor JD, II, Burghardt JR, Burghardt RC, Johnson GA (2006) Glycosylation dependent cell adhesion molecule 1-like protein and l-selectin expression in sheep interplacentomal and placentomal endometrium. Reproduction 131, 751-761.
| Crossref | Google Scholar | PubMed |

Okumu LA, Forde N, Fahey AG, Fitzpatrick E, Roche JF, Crowe MA, Lonergan P (2010) The effect of elevated progesterone and pregnancy status on mRNA expression and localisation of progesterone and oestrogen receptors in the bovine uterus. Reproduction 140, 143-153.
| Crossref | Google Scholar | PubMed |

O’Neill LAJ, Kishton RJ, Rathmell J (2016) A guide to immunometabolism for immunologists. Nature Reviews Immunology 16, 553-565.
| Crossref | Google Scholar | PubMed |

Park TJ, Reznick J, Peterson BL, Blass G, Omerbašić D, Bennett NC, Kuich PHJL, Zasada C, Browe BM, Hamann W, Applegate DT, Radke MH, et al. (2017) Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat. Science 356, 307-311.
| Crossref | Google Scholar | PubMed |

Pohler KG, Geary TW, Johnson CL, Atkins JA, Jinks EM, Busch DC, Green JA, MacNeil MD, Smith MF (2013) Circulating bovine pregnancy associated glycoproteins are associated with late embryonic/fetal survival but not ovulatory follicle size in suckled beef cows. Journal of Animal Science 91, 4158-4167.
| Crossref | Google Scholar | PubMed |

Pohler KG, Pereira MHC, Lopes FR, Lawrence JC, Keisler DH, Smith MF, Vasconcelos JLM, Green JA (2016) Circulating concentrations of bovine pregnancy-associated glycoproteins and late embryonic mortality in lactating dairy herds. Journal of Dairy Science 99, 1584-1594.
| Crossref | Google Scholar | PubMed |

Reese ST, Pereira MHC, Edwards JL, Vasconcelos JLM, Pohler KG (2018) Pregnancy diagnosis in cattle using pregnancy associated glycoprotein concentration in circulation at day 24 of gestation. Theriogenology 106, 178-185.
| Crossref | Google Scholar | PubMed |

Reimers TJ, Ullmann MB, Hansel W (1985) Progesterone and prostanoid production by bovine binucleate trophoblastic cells. Biology of Reproduction 33, 1227-1236.
| Crossref | Google Scholar | PubMed |

Reynolds LP, Biondini ME, Borowicz PP, Vonnahme KA, Caton JS, Grazul-Bilska AT, Redmer DA (2005) Functional significance of developmental changes in placental microvascular architecture. Endothelium 12, 11-19.
| Crossref | Google Scholar | PubMed |

Ruder CA, Stellflug JN, Dahmen JJ, Sasser RG (1988) Detection of pregnancy in sheep by radioimmunoassay of sera for pregnancy-specific protein B. Theriogenology 29, 905-912.
| Crossref | Google Scholar | PubMed |

Ruoslahti E, Noble NA, Kagami S, Border WA (1994) Integrins. Kidney International 44, S17-S22.
| Google Scholar | PubMed |

Sasser RG, Ruder CA, Ivani KA, Butler JE, Hamilton WC (1986) Detection of pregnancy by radioimmunoassay of a novel pregnancy-specific protein in serum of cows and a profile of serum concentrations during gestation. Biology of Reproduction 35, 936-942.
| Crossref | Google Scholar | PubMed |

Satterfield MC, Bazer FW, Spencer TE (2006) Progesterone regulation of preimplantation conceptus growth and galectin 15 (LGALS15) in the ovine uterus. Biology of Reproduction 75, 289-296.
| Crossref | Google Scholar | PubMed |

Seo H, Bazer FW, Burghardt RC, Johnson GA (2019) Immunohistochemical examination of trophoblast syncytialization during early placentation in sheep. International Journal of Molecular Sciences 20, 4530-4543.
| Crossref | Google Scholar | PubMed |

Seo H, Frank JW, Burghardt RC, Bazer FW, Johnson GA (2020) Integrins and OPN localize to adhesion complexes during placentation in sheep. Reproduction 160, 521-532.
| Crossref | Google Scholar | PubMed |

Seo H, Bazer FW, Johnson GA (2023) ‘Early syncytialization of the ovine placenta revisited.’ (Springer Nature)

Simintiras CA, Sanchez JM, McDonald M, O’Callaghan E, Aburima AA, Lonergan P (2021) Conceptus metabolomic profiling reveals stage-specific phenotypes leading up to pregnancy recognition in cattle. Biology of Reproduction 104, 1022-1033.
| Crossref | Google Scholar |

Simmons RM, Erikson DW, Kim J, Burghardt RC, Bazer FW, Johnson GA, Spencer TE (2009) Insulin-like growth factor binding protein-1 in the ruminant uterus: potential endometrial marker and regulator of conceptus elongation. Endocrinology 150, 4295-4305.
| Crossref | Google Scholar | PubMed |

Smith BD, Poliakiwski B, Polanco O, Singleton S, de Melo GD, Muntari M, Oliveira Filho RV, Pohler KG (2022) Decisive points for pregnancy losses in beef cattle. Reproduction, Fertility and Development 35, 70-83.
| Crossref | Google Scholar | PubMed |

Spencer TE, Bazer FW (2002) Biology of progesterone action during pregnancy recognition and maintenance of pregnancy. Frontiers in Bioscience 7, 1879-1898.
| Crossref | Google Scholar |

Spencer TE, Hansen TR (2015) Implantation and establishment of pregnancy in ruminants. In ‘Regulation of implantation and establishment of pregnancy in mammals, Vol. 216’. Advances in Anatomy, Embryology and Cell Biology. (Eds R Geisert, F Bazer) pp. 105–135. (Springer)

Spencer TE, Bartol FF, Bazer FW, Johnson GA, Joyce MM (1999) Identification and characterization of glycosylation-dependent cell adhesion molecule 1-like protein expression in the ovine uterus. Biology of Reproduction 60, 241-250.
| Crossref | Google Scholar | PubMed |

Spencer TE, Johnson GA, Bazer FW, Burghardt RC (2004a) Implantation mechanisms: insights from the sheep. Reproduction 128, 657-668.
| Crossref | Google Scholar | PubMed |

Spencer TE, Johnson GA, Burghardt RC, Bazer FW (2004b) Progesterone and placental hormone actions on the uterus: insights from domestic animals. Biology of Reproduction 71, 2-10.
| Crossref | Google Scholar |

Spencer TE, Johnson GA, Bazer FW, Burghardt RC (2007a) Fetal-maternal interactions during the establishment of pregnancy in ruminants. Society of Reproduction and Fertility Supplement 64, 379-396.
| Crossref | Google Scholar | PubMed |

Spencer TE, Johnson GA, Bazer FW, Burghardt RC, Palmarini M (2007b) Pregnancy recognition and conceptus implantation in domestic ruminants: roles of progesterone, interferons and endogenous retroviruses. Reproduction, Fertility and Development 19, 65-78.
| Crossref | Google Scholar | PubMed |

Stenhouse C, Seo H, Wu G, Johnson GA, Bazer FW (2022) Insights into the regulation of implantation and placentation in humans, rodents, sheep, and pigs. In ‘Recent advances in animal nutrition and metabolism, Vol. 1354’. Advances in Experimental Medicine and Biology. (Ed. G Wu) pp. 25–48. (Springer)

Wales RG, Cuneo CL (1989) Morphology and chemical analysis of the sheep conceptus from the 13th to the 19th day of pregnancy. Reproduction, Fertility and Development 1, 31-39.
| Crossref | Google Scholar | PubMed |

Wallace RM, Pohler KG, Smith MF, Green JA (2015) Placental PAGs: gene origins, expression patterns, and use as markers of pregnancy. Reproduction 149, R115-R126.
| Crossref | Google Scholar | PubMed |

Wang X, Johnson GA, Burghardt RC, Wu G, Bazer FW (2014) Uterine histotroph and conceptus development. I. Cooperative effects of arginine and secreted phosphoprotein 1 on proliferation of ovine trophectoderm cells via activation of the PDK1-Akt/PKB-TSC2-MTORC1 signaling cascade. Biology of Reproduction 92, 51.
| Crossref | Google Scholar | PubMed |

Wang X, Johnson GA, Burghardt RC, Wu G, Bazer FW (2016) Uterine histotroph and conceptus development. II. Arginine and secreted phosphoprotein 1 cooperatively stimulate migration and adhesion of ovine trophectoderm cells via focal adhesion-MTORC2 mediated cytoskeleton reorganization. Biology of Reproduction 95, 71.
| Crossref | Google Scholar |

Wathes DC, Wooding FBP (1980) An electron microscopic study of implantation in the cow. American Journal of Anatomy 159, 285-306.
| Crossref | Google Scholar | PubMed |

Wiltbank MC, Baez GM, Garcia-Guerra A, Toledo MZ, Monteiro PLJ, Melo LF, Ochoa JC, Santos JEP, Sartori R (2016) Pivotal periods for pregnancy loss during the first trimester of gestation in lactating dairy cows. Theriogenology 86, 239-253.
| Crossref | Google Scholar | PubMed |

Wimsatt WA (1951) Observations on the morphogenesis, cytochemistry, and significance of the binucleate giant cells of the placenta of ruminants. American Journal of Anatomy 89, 233-281.
| Crossref | Google Scholar | PubMed |

Wooding FB (1982a) The role of the binucleate cell in ruminant placental structure. Journal of Reproduction and Fertility Supplement 31, 31-39.
| Google Scholar | PubMed |

Wooding FB (1982b) Structure and function of placental binucleate (‘giant’) cells. Bibliotheca Anatom 22, 134-139.
| Google Scholar |

Wooding FBP (1984) Role of binucleate cells in fetomaternal cell fusion at implantation in the sheep. American Journal of Anatomy 170, 233-250.
| Crossref | Google Scholar | PubMed |

Wooding FBP (1992) Current topic: The synepitheliochorial placenta of ruminants: binucleate cell fusions and hormone production. Placenta 13, 101-113.
| Crossref | Google Scholar | PubMed |

Wooding FBP (2022) The ruminant placental trophoblast binucleate cell: an evolutionary breakthrough. Biology of Reproduction 107, 705-716.
| Crossref | Google Scholar | PubMed |

Wooding FB, Burton GJ (2008) Chapter 6: Synepitheliochorial placentation: ruminants (ewe and cow). In ‘Comparative placentation: structure, function and evolution’. pp. 133–167. (Springer-Verlag: Heidelberg)

Wooding FBP, Wathes DC (1980) Binucleate cell migration in the bovine placentome. Journal of Reproduction and Fertility 59, 425-430.
| Crossref | Google Scholar | PubMed |

Wooding FBP, Flint APF, Heap RB, Morgan G, Buttle HL, Young IR (1986) Control of binucleate cell migration in the placenta of sheep and goats. Journal of Reproduction and Fertility 76, 499-512.
| Crossref | Google Scholar | PubMed |

Wooding FBP, Fowden AL, Bell AW, Ehrhardt RA, Limesand SW, Hay WW (2005a) Localisation of glucose transport in the ruminant placenta: implications for sequential use of transporter isoforms. Placenta 26, 626-640.
| Crossref | Google Scholar | PubMed |

Wooding FBP, Roberts RM, Green JA (2005b) Light and electron microscope immunocytochemical studies of the distribution of pregnancy associated glycoproteins (PAGs) throughout pregnancy in the cow: possible functional implications. Placenta 26, 807-827.
| Crossref | Google Scholar | PubMed |

Wu G, Bazer FW, Davis TA, Kim SW, Li P, Marc Rhoads J, Carey Satterfield M, Smith SB, Spencer TE, Yin Y (2009) Arginine metabolism and nutrition in growth, health and disease. Amino Acids 37, 153-168.
| Crossref | Google Scholar | PubMed |

Wu Z, Hou Y, Hu S, Bazer FW, Meininger CJ, McNeal CJ, Wu G (2016) Catabolism and safety of supplemental L-arginine in animals. Amino Acids 48, 1541-1552.
| Crossref | Google Scholar | PubMed |