Mouse is the new woman? Translational research in reproductive immunology

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This review compares pregnancy complications and endometriosis models in women and mice, concluding that female mice are good analogs for human reproductive immunology research.

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This review examines how the maternal immune response to paternal antigens at the embryo–feto/placental interface contributes to pregnancy complications, comparing human outcomes with laboratory mouse models for conditions such as implantation failure, recurrent spontaneous abortion, pre-eclampsia, intrauterine growth restriction, and premature labor. It emphasizes that pregnancy immunology is shaped by prior exposure to paternal seminal plasma and the resulting “helpful” rather than harmful immune programming, while focusing on uterine–placental immune cross-talk at the intrauterine interface. The paper’s major caveat is that translational analogs must be validated with human studies, and it explicitly notes that bidirectional transplacental traffic of immune cells is not discussed due to limited data. It also compares an artificially induced mouse model of endometriosis (linked to infertility) with what occurs in women. This paper is centrally about endometriosis—reviewing the translational similarity of an induced mouse endometriosis model to human disease in the context of infertility and immune cross-talk.

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Abstract

In an outbred mating typical of human reproduction, the embryo and feto-placental unit express paternal antigens to which the mother's immune system can react. However, the embryo and feto-placental unit can engineer the maternal immune defense system towards helpful rather than harmful reactions. Indeed, this begins with the prospective mother's exposure to paternal seminal plasma. In this review, the pregnancy complications of implantation failure (infertility), recurrent spontaneous abortion, pre-eclampsia and intrauterine growth restriction, and premature labor are examined to determine the degree of similarity between events in women and events in lab mouse models. The artificially induced model of endometriosis (which contributes to infertility) is also compared to what occurs in women. One may conclude that the female mouse provides a good analog of the human female. Nevertheless, it is always important to validate mouse data with human studies. The discussion focuses on the intrauterine interface between embryonic and placental tissues and maternal uterine tissues and the dialogue that is referred to as cross-talk. Issues relating to bidirectional transplacental traffic of immune system cells are not discussed as there is very little relevant data.
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Abstract

In an outbred mating typical of human reproduction, the embryo and feto-placental unit express paternal antigens to which the mother’s immune system can react. However, the embryo and feto-placental unit can engineer the maternal immune defense system towards helpful rather than harmful reactions. Indeed, this begins with the prospective mother’s exposure to paternal seminal plasma. In this review, the pregnancy complications of implantation failure (infertility), recurrent spontaneous abortion, pre-eclampsia and intrauterine growth restriction, and premature labor are examined to determine the degree of similarity between events in women and events in lab mouse models. The artificially induced model of endometriosis (which contributes to infertility) is also compared to what occurs in women. One may conclude that the female mouse provides a good analog of the human female. Nevertheless, it is always important to validate mouse data with human studies. The discussion focuses on the intrauterine interface between embryonic and placental tissues and maternal uterine tissues and the dialogue that is referred to as cross-talk. Issues relating to bidirectional transplacental traffic of immune system cells are not discussed as there is very little relevant data. Similar content being viewed by others Abbreviations - APC: - Antigen-presenting cell - EVT: - Extravillous trophoblasts - EVTP: - Endovascular trophoblast plugs - NK: - Natural killer - uNK: - Uterine NK cell subdivided into‚ true uterine NK cells (TuNKs) and‚ blood-type uterine NK cells (BuNKs) - PMNL: - Polymorphonuclear leukocyte or neutrophil - IVIG: - Intravenous immunoglobilin G - LIT: - Mononuclear leukocyte immunotherapy - hCG: - Human chorionic gonadotropin - sflt-1: - Soluble VEGF receptor - Teff: - Effector T cell - Tregs: - Regulatory T cells - TcR: - T cell receptor - IVFET: - In vitro fertilization and embryo transfer - MHC: - Major histocompatibility complex (antigens) - KIR: - Killer-cell immunoglobulin-like receptors - IUGR: - Intrauterine growth restriction - RIF: - Recurrent implantation failure - RSA: - Recurrent spontaneous abortion - CSF: - Colony stimulating factor

References

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Am J Obstet Gynecol 182:1404–1413 Murphy SP, Hanna NH, Fast LD, Shaw SK, Berg G, Padbury JF, Romero R, Sharma S (2009) Evidence for participation of uterine natural killer cells in the mechanisms responsible for spontaneous preterm labor and delivery. Am J Obstst Gynecol 200:308.e1–3408.e9 Phillippe M, Diamond AK, Sweet LM, Oppenheimer KH, Bradley DF (2011) Expression of coagulation-related protein genes during LPS-induced preterm delivery in the pregnant mouse. Reprod Sci 18:1071–1079 Boyle AK, Rinaldi SF, Thomson AJ, Rossi AG, Saunders PT, Norman JE (2015) Statin treatment in a novel infection-induced mouse model of preterm birth. J Reprod Immunol 111:16 Author information Authors and Affiliations Corresponding author Additional information This article is related to Fetomaternal Cross Talk and its Effect on Pregnancy Maintenance Maternal and Offspring Health – Guest Editor: Petra Arck Rights and permissions About this article Cite this article Clark, D.A. Mouse is the new woman? Translational research in reproductive immunology. Semin Immunopathol 38, 651–668 (2016). https://doi.org/10.1007/s00281-015-0553-x Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s00281-015-0553-x

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endometriosis

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Immunity Reproduction Reproductive Physiological Phenomena Translational Research, Biomedical Abortion, Habitual Abortion, Habitual Abortion, Habitual Animals Disease Models, Animal Embryo Implantation Embryo Implantation Endometriosis Endometriosis Endometriosis Endometriosis Female Humans Immune System Immune System Immune System

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