The enunciation of the T helper 1/T helper 2 (Th1/Th2) paradigm in pregnancy has represented a major step forward in our understanding of physiological and pathologic materno-foetal relationship. ...However, recent developments in studies of the implantation process and in the emergence of the uterine vascular bed and its control by natural killer cells and cytokines suggest that one must go beyond this hitherto useful scheme. In this review, we replace the emergence of the paradigm in its historical context and then emphasises what it does explain and what it no longer account for. A final reappraisal of the paradigm is suggested.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract This review summarises an invited talk presented at the 2012 ESRI/ASRI meeting in Hamburg, concerning current views of inflammation in pregnancy, which is timely given that the effects of a ...local injury in the uterus acts to favour implantation. Recalling that inflammation can be good (it is useful and necessary for implantation), bad (in implantation failure, RSA) and ugly (at the extreme, endometriosis is associated with pain and infertility) leads to consideration of its status in pregnancy. Its role in implantation and the fact that pregnancy maintains some aspects of inflammation throughout, leads to revision of not only concepts of immunosuppression and the Th1/Th2 paradigm, but also the feto-maternal relationship as seen since Medawar's hypotheses were advanced. This is examined from an evolutionary perspective, which should lead to further review of our perception of uterine NK cells, and the emergence of Treg cells to control some aspects of adaptive immunity, which appeared long after placentation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Highlights • In opposition to Medawar, placentae exist in invertebrates and above all vertebrates that can reject grafts: see for example the shark “foetal allograft”: no problems. • Placentation ...exists but does not last long in marsupials: is it because of the threat of a T cell and T cell cytokine attack–also activating NK cells? • Inflammation is needed in implantation but post-implantation must be controlled by Tregs. However, some inflammatory components persist post-implantation in humans. • T cells can be downregulated by complement. • Thus, in human pregnancy continuous controlled inflammation (linked to deep invasion?) exists and alloantigen-specific Treg control may be “borderline” in a first pregnancy. • Model: in great apes, with deep invasion placenta, failure of Treg control or a complement activation (thus Treg downregulation) leads to continuous excess inflammation in PE, more abrupt even in cases of recurrent spontaneous abortion.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract In this short remembrance paper, I survey (what I believe are) key events in the evolution of the concepts of preeclampsia from the first workshop in 1998 to the 2012 one, and from Tahiti to ...Reunion island, via Mauritius and Tioman Island.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In this review, we first revisit the original concept of "suppressor T-cells" in pregnancy, put it in a historical perspective, and then highlight the main data that licensed its resurrection and ...revision into the concept of "regulatory T-cells" (Tregs) in pregnancy. We review the evidence for a major role of Tregs in murine and human pregnancy and discuss Treg interactions with dendritic and uterine natural killer cells, other players of maternal-fetal tolerance. Finally, we highlight what we consider as the most important questions in the field.
Primipaternities and human birthweights Robillard, Pierre-Yves; Dekker, Gustaaf; Chaouat, Gérard ...
Journal of reproductive immunology,
September 2021, 2021-Sep, 2021-09-00, 20210901, Volume:
147
Journal Article
Peer reviewed
•It has been knowned for 160 years that primiparas have lighter babies than multiparas.•In this study, we show that there is an identical phenomenon in case of new paternity in multiparas.•First ...pregnancy at a level of a couple (“primipaternity”) may include and explain the well-known effect of primiparas having lighter babies than multiparas.
To investigate in singleton multiparous pregnancies the effect of having a new father for an index pregnancy on new-borns’ birthweights and intrauterine growth restriction.
20 year-observational cohort study (2001–2020).
Centre Hospitalier Universitaire Hospitalier Sud Reunion’s maternity (French overseas department, Indian Ocean).
Comparing the 811 multiparas (cases) who had a new partner with the 49,712 who did not (controls), there were no differences concerning maternal age, education, ovulation induction/IVF, previous miscarriages, exams during pregnancies, pre-pregnancy BMI, gestational diabetes, and chronic hypertension. Cases had more previous pregnancies than controls (gravidity 4.2 vs 2.8, p < 0.001), volunteer abortions (OR1.93, p < 0.001), in vitro fecundations (OR 4.34, p < 0.001), were more likely to be unmarried (OR 2.94, p < 0.001) smoker (OR 2.2, p < 0.0001) and consuming alcohol during pregnancy (OR 2.35, p = 0.001). Cases had a much higher risk of preeclampsia than controls (OR 3.94, p < 0.001), especially early-onset preeclampsia (< 34 weeks) with an OR 4.1 (p < 0.001). Controlling for confounding factors (preeclampsia, smoking, alcohol use, early prematurity < 33 weeks, maternal ethnicity), primipaternity was an independent factor for small for gestational age newborns (OR 1.48, p < 0.001).
It has been known for decades that primiparas have lighter babies than multiparas. Primipaternity represents also a risk for lower birth weights. Human birthweight seems to be linked with a “couple habituation” (to paternal genes) which may be not fully established in the first pregnancy of the couple.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
8.
Cytokines: Important for implantation? Chaouat, Gérard; Dubanchet, Sylvie; Ledée, Nathalie
Journal of assisted reproduction and genetics,
11/2007, Volume:
24, Issue:
11
Journal Article
Peer reviewed
Open access
Cytokines are obviously very important in an established pregnancy, but what about human embryo implantation?
Literature review.
We first discuss the necessity and limits of animal models, and then ...review the few cytokines which have been demonstrated by knock-out methods to be absolutely necessary for embryo implantation using in animal models. We then review what is known or discussed about the role of other cytokines as deduced from quantitative and/or qualitative dysregulation in animals and in humans.
Cytokines are indeed involved in implantation as they are in ongoing pregnancy and delivery. Relevance to infertility and recurrent pregnancy loss is discussed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The 11th workshop on Immunology of preeclampsia in Reunion 2018 celebrated its 20th candle In this paper we try to summarize the main tracks of reflections during these two decades. First, of course, ...the advances in immunology of reproduction in the field of preeclampsia, which was poorly developed 2 decades ago when we first started in 1998. But, this workshop has not been dedicated only to immunology. Second, one of the main reflections has always been, workshop after workshop: “why does preeclampsia exists in humans?” in an evolutionary view, as we have no established natural animal models in the other some 4500 other mammal species. Third, besides the reflections on the biological plausibility of preeclampsia-disease-of-first-pregnancies-at-a-level-of-a-couple (primipaternity rather than primigravidity), i.e. immunology, paternal-maternal conflict, we had to face an apparent conundrum: the human species should have disappeared (almost 40–50% incidence of hypertensive disorders of pregnancy in couples conceiving within the first 4 months of sexual cohabitation). We report then the dialogues we were obliged to have with zoologists who themselves had no clues on our apparent “extravagant sexuality” and strange reproduction (ridiculous low fertility rate of the human female: 25%). Fourth, debates on the main difference between early onset (“rather immunological”) and late onset PE (“rather maternal vascular predispositions”). Further, the debate of why high income countries report 90% of their PE being LOP, while other countries describe epidemiologically very high incidences of EOP. Finally, and always present at all workshops, the physiopathology of the reversible systemic maternal vascular inflammation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Regulatory T cells (Tregs) play crucial roles in both fetal and tumor development. We recently showed that immunosurveillance by pre-existing CD44(high)CD62L(low) activated/memory Tregs (amTregs) ...specific for self-Ags protects emergent tumor cells in mice. This Treg response of a memory type is more rapid than and dominates the antitumor response of tumor-specific effector T cells. In this study, we report striking similarities between the early Treg responses to embryo and tumor implantation. Tregs are rapidly recruited to uterus-draining lymph nodes and activated in the first days after embryo implantation in both syngeneic and allogeneic matings; express the markers of the amTreg subset; and are at least in part self-Ag specific, as seen in tumor emergence. Unlike in the tumor emergence setting, however, for which preimmunization against tumor Ags is sufficient for complete tumor eradication even in the presence of Tregs, Treg depletion is additionally required for high frequencies of fetus loss after preimmunization against paternal tissue Ags. Thus, amTregs play a major role in protecting embryos in both naive and preimmune settings. This role and the ensuing therapeutic potential are further highlighted by showing that Treg stimulation, directly by low-dose IL-2 or indirectly by Fms-related tyrosine kinase 3 ligand, led to normal pregnancy rates in a spontaneous abortion-prone model.
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