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Reproduction (Cambridge, England)2016; 152(3); 171-184; doi: 10.1530/REP-16-0236

Convergent evolution of pregnancy-specific glycoproteins in human and horse.

Abstract: Pregnancy-specific glycoproteins (PSGs) are members of the carcinoembryonic antigen cell adhesion molecule (CEACAM) family that are secreted by trophoblast cells. PSGs may modulate immune, angiogenic and platelet responses during pregnancy. Until now, PSGs are only found in species that have a highly invasive (hemochorial) placentation including humans, mice and rats. Surprisingly, analyzing the CEACAM gene family of the horse, which has a non-invasive epitheliochorial placenta, with the exception of the transient endometrial cups, we identified equine CEACAM family members that seem to be related to PSGs of rodents and primates. We identified seven genes that encode secreted PSG-like CEACAMs Phylogenetic analyses indicate that they evolved independently from an equine CEACAM1-like ancestor rather than from a common PSG-like ancestor with rodents and primates. Significantly, expression of PSG-like genes (CEACAM44, CEACAM48, CEACAM49 and CEACAM55) was found in non-invasive as well as invasive trophoblast cells such as purified chorionic girdle cells and endometrial cup cells. Chorionic girdle cells are highly invasive trophoblast cells that invade the endometrium of the mare where they form endometrial cups and are in close contact with maternal immune cells. Therefore, the microenvironment of invasive equine trophoblast cells has striking similarities to the microenvironment of trophoblast cells in hemochorial placentas, suggesting that equine PSG-like CEACAMs and rodent and primate PSGs have undergone convergent evolution. This is supported by our finding that equine PSG-like CEACAM49 exhibits similar activity to certain rodent and human PSGs in a functional assay of platelet-fibrinogen binding. Our results have implications for understanding the evolution of PSGs and their functions in maternal-fetal interactions.
Publication Date: 2016-06-08 PubMed ID: 27280409DOI: 10.1530/REP-16-0236Google Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research paper discusses the evolution of pregnancy-specific glycoproteins (PSGs) found in horse and human species. Teachers suggest that these proteins have independently evolved in horses from an equine ancestor — not from a common ancestor with rodents and primates. This research contributes to understanding the evolution of PSGs and how they function in maternal-fetal interactions.

Objective of the Research

  • The main goal of the study was to investigate the evolutionary lineage of pregnancy-specific glycoproteins (PSGs) in horses and humans.
  • The researchers aimed at understanding if these proteins emerged from a common ancestor with rodents and primates or if they evolved independently.
  • The team was also keen to understand the implications of the evolution of these PSGs in maternal-fetal interactions.

Methodology

  • Researchers analyzed the carcinoembryonic antigen cell adhesion molecule (CEACAM) gene family of the horse, which has a non-invasive epitheliochorial placenta, except for the transient endometrial cups.
  • They identified seven genes that encode secreted PSG-like CEACAMs and conducted phylogenetic analyses to understand their evolutionary history.
  • The team also assessed the expression of PSG-like genes in non-invasive as well as invasive trophoblast cells, such as purified chorionic girdle cells and endometrial cup cells.

Findings

  • The study found that horses possess PSG-like proteins, although they have a non-invasive placenta. This discovery was made upon analyzing the CEACAM gene family of the horse.
  • The phylogenetic analysis suggests that these proteins have evolved independently from an equine CEACAM1-like ancestor rather than from a common ancestor shared with rodents and primates.
  • The expression of PSG-like genes was discovered in both non-invasive and invasive trophoblast cells, hinting at a similar function to PSGs in other species.
  • Chorionic girdle cells, which contain PSG-like proteins, reveal a microenvironment that mirrors the one found in invasive trophoblast cells of species with highly invasive (hemochorial) placentation. This discovery suggests possible convergent evolution of these proteins.
  • Moreover, the finding that equine PSG-like CEACAM49 exhibits behavior similar to certain rodent and human PSGs in a functional assay of platelet-fibrinogen binding further supports this idea.

Implications

  • This research provides critical insights into the evolution of pregnancy-specific glycoproteins, particularly in species that do not share a common PSG-like ancestor.
  • More significantly, it adds to the understanding of the role of PSGs in maternal-fetal interactions, possibly paving the way for improved reproductive health management protocols.

Cite This Article

APA
Aleksic D, Blaschke L, Mißbach S, Hänske J, Weiß W, Handler J, Zimmermann W, Cabrera-Sharp V, Read JE, de Mestre AM, O'Riordan R, Moore T, Kammerer R. (2016). Convergent evolution of pregnancy-specific glycoproteins in human and horse. Reproduction, 152(3), 171-184. https://doi.org/10.1530/REP-16-0236

Publication

ISSN: 1741-7899
NlmUniqueID: 100966036
Country: England
Language: English
Volume: 152
Issue: 3
Pages: 171-184

Researcher Affiliations

Aleksic, Denis
  • Institute of ImmunologyFriedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
Blaschke, Lisa
  • Institute of ImmunologyFriedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
Mißbach, Sophie
  • Institute of ImmunologyFriedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
Hänske, Jana
  • Institute of ImmunologyFriedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
Weiß, Wiebke
  • Institute of ImmunologyFriedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
Handler, Johannes
  • Equine Center Bad SaarowFreie Universität Berlin, Bad Saarow, Germany.
Zimmermann, Wolfgang
  • Tumor Immunology LaboratoryLudwig-Maximilians-University, Munich, Germany Department of UrologyUniversity Hospital, Munich, Germany.
Cabrera-Sharp, Victoria
  • Department of Comparative Biomedical SciencesThe Royal Veterinary College, University of London, London, UK.
Read, Jordan E
  • Department of Comparative Biomedical SciencesThe Royal Veterinary College, University of London, London, UK.
de Mestre, Amanda M
  • Department of Comparative Biomedical SciencesThe Royal Veterinary College, University of London, London, UK.
O'Riordan, Ronan
  • School of Biochemistry and Cell BiologyUniversity College Cork, Cork, Ireland.
Moore, Tom
  • School of Biochemistry and Cell BiologyUniversity College Cork, Cork, Ireland.
Kammerer, Robert
  • Institute of ImmunologyFriedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany Robert.Kammerer@fli.bund.de.

MeSH Terms

  • Animals
  • Biological Evolution
  • Carcinoembryonic Antigen / metabolism
  • Female
  • Glycoproteins / classification
  • Glycoproteins / metabolism
  • Horses
  • Humans
  • Phylogeny
  • Placenta / metabolism
  • Pregnancy
  • Pregnancy Proteins / metabolism
  • Trophoblasts / metabolism

Grant Funding

  • Wellcome Trust

Citations

This article has been cited 11 times.
  1. Kammerer R, Zimmermann W. Two waves of evolution in the rodent pregnancy-specific glycoprotein (Psg) gene family lead to structurally diverse PSGs. BMC Genomics 2023 Aug 21;24(1):468.
    doi: 10.1186/s12864-023-09560-6pubmed: 37605167google scholar: lookup
  2. Yohannes E, Ippolito DL, Damicis JR, Dornisch EM, Leonard KM, Napolitano PG, Ieronimakis N. Longitudinal Proteomic Analysis of Plasma across Healthy Pregnancies Reveals Indicators of Gestational Age. Int J Mol Sci 2022 Jun 25;23(13).
    doi: 10.3390/ijms23137076pubmed: 35806078google scholar: lookup
  3. Liu X, Gao W, Liu W. Identification of KLF6/PSGs and NPY-Related USF2/CEACAM Transcriptional Regulatory Networks via Spinal Cord Bulk and Single-Cell RNA-Seq Analysis. Dis Markers 2021;2021:2826609.
    doi: 10.1155/2021/2826609pubmed: 34880956google scholar: lookup
  4. Antczak DF, Allen WRT. Placentation in Equids. Adv Anat Embryol Cell Biol 2021;234:91-128.
    doi: 10.1007/978-3-030-77360-1_6pubmed: 34694479google scholar: lookup
  5. Zimmermann W, Kammerer R. The immune-modulating pregnancy-specific glycoproteins evolve rapidly and their presence correlates with hemochorial placentation in primates. BMC Genomics 2021 Feb 18;22(1):128.
    doi: 10.1186/s12864-021-07413-8pubmed: 33602137google scholar: lookup
  6. Deng L, Han Y, Tang C, Liao Q, Li Z. Label-Free Mass Spectrometry-Based Quantitative Proteomics Analysis of Serum Proteins During Early Pregnancy in Jennies (Equus asinus). Front Vet Sci 2020;7:569587.
    doi: 10.3389/fvets.2020.569587pubmed: 33195553google scholar: lookup
  7. Hänske J, Hammacher T, Grenkowitz F, Mansfeld M, Dau TH, Maksimov P, Friedrich C, Zimmermann W, Kammerer R. Natural selection supports escape from concerted evolution of a recently duplicated CEACAM1 paralog in the ruminant CEA gene family. Sci Rep 2020 Feb 25;10(1):3404.
    doi: 10.1038/s41598-020-60425-4pubmed: 32099040google scholar: lookup
  8. Mißbach S, Aleksic D, Blaschke L, Hassemer T, Lee KJ, Mansfeld M, Hänske J, Handler J, Kammerer R. Alternative splicing after gene duplication drives CEACAM1-paralog diversification in the horse. BMC Evol Biol 2018 Mar 15;18(1):32.
    doi: 10.1186/s12862-018-1145-xpubmed: 29544443google scholar: lookup
  9. Carter AM. Evolution of Placental Hormones: Implications for Animal Models. Front Endocrinol (Lausanne) 2022;13:891927.
    doi: 10.3389/fendo.2022.891927pubmed: 35692413google scholar: lookup
  10. Kammerer R, Ballesteros A, Bonsor D, Warren J, Williams JM, Moore T, Dveksler G. Equine pregnancy-specific glycoprotein CEACAM49 secreted by endometrial cup cells activates TGFB. Reproduction 2020 Nov;160(5):685-694.
    doi: 10.1530/REP-20-0277pubmed: 33065543google scholar: lookup
  11. Kammerer R, Mansfeld M, Hänske J, Mißbach S, He X, Köllner B, Mouchantat S, Zimmermann W. Recent expansion and adaptive evolution of the carcinoembryonic antigen family in bats of the Yangochiroptera subgroup. BMC Genomics 2017 Sep 11;18(1):717.
    doi: 10.1186/s12864-017-4106-7pubmed: 28893191google scholar: lookup