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Reproductive immunology: the only good model for humans is… homo sapiens sapiens
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Abstract / Journal of Reproductive Immunology 101–102 (2014) 6–17
of preeclamptic patients. Furthermore, sEng appeared to exacerbate the vascular damage mediated by sFlt1 in pregnant rats, resulting in severe preeclampsia-like illness, including the development of thrombocytopenia and fetal growth restriction. Measurement of angiogenic markers in the serum/plasma is particularly useful for the diagnosis and prediction of preterm preeclampsia. Methods aimed at interfering with sFlt1 and/or sEng actions may be a novel therapeutic strategy in severe preterm preeclampsia. http://dx.doi.org/10.1016/j.jri.2013.12.011 S11 Tom Rademacher Department of Immunology and Molecular Pathology, Molecular Medicine Unit, Royal Free and University College London Medical School, London, UK (No abstract has been submitted) http://dx.doi.org/10.1016/j.jri.2013.12.012 S12 Only humans have human placentas Udo R. Markert ∗ , Stephanie Ospina-Prieto, Wittaya Chaiwangyen, André Schmidt, Diana M. Morales-Prieto Placenta-Lab, Department of Obstetrics, University Hospital Jena, Germany The placenta is probably the organ with the highest variability among different species. It differs in shape, size, and number of layers between fetal and maternal blood. During the last decade, a novel difference has been discovered: the microRNA (miRNA) profile is widely diverse and varies even among very close species. Placental miRNAs appeared late in evolution and can only be found in eutherian mammals. Nevertheless, these miRNAs are constantly under evolutionary pressure. As a result, miRNA sequences and their mRNA targets may differ among species. Even when the same miRNA is expressed in different species, the target mRNA, and especially the miRNA seed region, mostly within the 3 UTR region, may still differ. Human placenta tissue exhibits a unique organ-specific miRNA expression pattern. For example, the large miRNA cluster on chromosome 19 (C19MC) is exclusively expressed in hominidae placentas, but in no other organs and species including mice and others that are frequently used as models for reproduction. A few other miRNAs are not even expressed in great apes, but only in humans, including in their placentas. In humans, trophoblast-derived C19MC miRNAs dynamically change during pregnancy and are expressed into the maternal plasma, from where they may exert systemic regulatory functions and where they will serve as novel biomarkers. Several placental miRNAs, such as the members of C19MC, are involved in or associated with preeclampsia, intrauterine growth restriction, preterm delivery, and other pregnancy disorders. It can be concluded that animal models for human placenta have a
different panel of miRNAs and targets, and their predictive value for the situation in humans seems to be limited. http://dx.doi.org/10.1016/j.jri.2013.12.013 S13 Reproductive immunology: the only good model for humans is. . . homo sapiens sapiens C.P. Gérard Chaouat Hôpital Saint Louis, Paris, France In this controversy, I will take the stand that the only good model for human studies is the human, for several reasons: (a) Although the rodent placenta is haemochorial, it differs from the human in its anatomical architecture, as well as in its invasion stages: notably, for example, “shallow invasion”, characteristic for some of a defect of the second wave of invasion in humans, in cases of preeclamptic placentae, but is not seen in rodents. (b) The expression of MHC antigens is different in human and rodents, where class I can be seen on the placental spongiotrophoblasts, namely H-2K, D, and L, whereas in the human the only polymorphic class I is HLA-C (whose polymorphism is real but limited). (c) HLA-G or HLA-G-like expression is seen only in humans and some great apes, since there is no real consensus that the HLA-G-equivalent candidates in rodents fulfil this role. (d) The only quasi-equivalent models are some great apes, which are close to our genders, but most of them (if not all) are endangered and thus protected species. Even AIDS studies are limited in this respect. The other monkeys species are too far from humans (for example, in some, Mamu-AG is a pseudo gene, although it can tell us something about the lack of an absolute requirement for HLA-G expression in apes, it also tells us that the human placenta cannot be mimicked 100% by such a species. (e) The repertoire of NK receptors in mice and human differs drastically. (f) The resorption in mice is not fully equivalent to human abortion. These and other arguments will be further developed during the session. http://dx.doi.org/10.1016/j.jri.2013.12.014 S14 Thomas Henry and Bishop Samuel at the feto-maternal interface David A. Clark McMaster University, Hamilton and University of Toronto, Ontario, Canada On Saturday, 30 June 1860 at the Oxford University Museum of Natural History, Thomas Henry Huxley debated
Abstract / Journal of Reproductive Immunology 101–102 (2014) 6–17
of preeclamptic patients. Furthermore, sEng appeared to exacerbate the vascular damage mediated by sFlt1 in pregnant rats, resulting in severe preeclampsia-like illness, including the development of thrombocytopenia and fetal growth restriction. Measurement of angiogenic markers in the serum/plasma is particularly useful for the diagnosis and prediction of preterm preeclampsia. Methods aimed at interfering with sFlt1 and/or sEng actions may be a novel therapeutic strategy in severe preterm preeclampsia. http://dx.doi.org/10.1016/j.jri.2013.12.011 S11 Tom Rademacher Department of Immunology and Molecular Pathology, Molecular Medicine Unit, Royal Free and University College London Medical School, London, UK (No abstract has been submitted) http://dx.doi.org/10.1016/j.jri.2013.12.012 S12 Only humans have human placentas Udo R. Markert ∗ , Stephanie Ospina-Prieto, Wittaya Chaiwangyen, André Schmidt, Diana M. Morales-Prieto Placenta-Lab, Department of Obstetrics, University Hospital Jena, Germany The placenta is probably the organ with the highest variability among different species. It differs in shape, size, and number of layers between fetal and maternal blood. During the last decade, a novel difference has been discovered: the microRNA (miRNA) profile is widely diverse and varies even among very close species. Placental miRNAs appeared late in evolution and can only be found in eutherian mammals. Nevertheless, these miRNAs are constantly under evolutionary pressure. As a result, miRNA sequences and their mRNA targets may differ among species. Even when the same miRNA is expressed in different species, the target mRNA, and especially the miRNA seed region, mostly within the 3 UTR region, may still differ. Human placenta tissue exhibits a unique organ-specific miRNA expression pattern. For example, the large miRNA cluster on chromosome 19 (C19MC) is exclusively expressed in hominidae placentas, but in no other organs and species including mice and others that are frequently used as models for reproduction. A few other miRNAs are not even expressed in great apes, but only in humans, including in their placentas. In humans, trophoblast-derived C19MC miRNAs dynamically change during pregnancy and are expressed into the maternal plasma, from where they may exert systemic regulatory functions and where they will serve as novel biomarkers. Several placental miRNAs, such as the members of C19MC, are involved in or associated with preeclampsia, intrauterine growth restriction, preterm delivery, and other pregnancy disorders. It can be concluded that animal models for human placenta have a
different panel of miRNAs and targets, and their predictive value for the situation in humans seems to be limited. http://dx.doi.org/10.1016/j.jri.2013.12.013 S13 Reproductive immunology: the only good model for humans is. . . homo sapiens sapiens C.P. Gérard Chaouat Hôpital Saint Louis, Paris, France In this controversy, I will take the stand that the only good model for human studies is the human, for several reasons: (a) Although the rodent placenta is haemochorial, it differs from the human in its anatomical architecture, as well as in its invasion stages: notably, for example, “shallow invasion”, characteristic for some of a defect of the second wave of invasion in humans, in cases of preeclamptic placentae, but is not seen in rodents. (b) The expression of MHC antigens is different in human and rodents, where class I can be seen on the placental spongiotrophoblasts, namely H-2K, D, and L, whereas in the human the only polymorphic class I is HLA-C (whose polymorphism is real but limited). (c) HLA-G or HLA-G-like expression is seen only in humans and some great apes, since there is no real consensus that the HLA-G-equivalent candidates in rodents fulfil this role. (d) The only quasi-equivalent models are some great apes, which are close to our genders, but most of them (if not all) are endangered and thus protected species. Even AIDS studies are limited in this respect. The other monkeys species are too far from humans (for example, in some, Mamu-AG is a pseudo gene, although it can tell us something about the lack of an absolute requirement for HLA-G expression in apes, it also tells us that the human placenta cannot be mimicked 100% by such a species. (e) The repertoire of NK receptors in mice and human differs drastically. (f) The resorption in mice is not fully equivalent to human abortion. These and other arguments will be further developed during the session. http://dx.doi.org/10.1016/j.jri.2013.12.014 S14 Thomas Henry and Bishop Samuel at the feto-maternal interface David A. Clark McMaster University, Hamilton and University of Toronto, Ontario, Canada On Saturday, 30 June 1860 at the Oxford University Museum of Natural History, Thomas Henry Huxley debated