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Maternal Tolerance (maternal + tolerance)

Distribution by Scientific Domains

Life Sciences	40%

Selected Abstracts

Reciprocal chemokine receptor and ligand expression in the human placenta: Implications for cytotrophoblast differentiation

DEVELOPMENTAL DYNAMICS, Issue 4 2004
Penelope M. Drake
Abstract At the onset of pregnancy, the human placenta, which forms the interface between the embryo/fetus and the mother, must rapidly develop into a life-sustaining organ. The many unusual processes entailed in placental development include the poorly understood phenomenon of maternal tolerance of the hemiallogeneic cells of the conceptus, including, most remarkably, placental trophoblasts that invade the uterine wall. To investigate whether this fetal organ exerts control over the maternal immune system at the level of leukocyte trafficking, we examined placental expression of chemokines, well-known cytokine regulators of leukocyte movements. In situ hybridization revealed abundant expression of 13 chemokines in the stromal but not the trophoblast compartment of chorionic villi. Potential roles for these molecules include recruitment of the resident macrophage (Hofbauer cell) population to the villi. In parallel, cytotrophoblast production of a panel of nine chemokine receptors was assessed by using RNase protection assays. The numerous receptors detected suggested the novel possibility that the paracrine actions of chemokine ligands derived from either the villous stroma or the decidua could mediate general aspects of placental development, with specific contributions to cytotrophoblast differentiation along the pathway that leads to uterine invasion. Developmental Dynamics 229:877,885, 2004. © 2004 Wiley-Liss, Inc. [source]

Functions of corticotropin-releasing hormone in anthropoid primates: From brain to placenta

AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 4 2006
Michael L. Power
Corticotropin-releasing hormone (CRH) is an ancient regulatory molecule. The CRH hormone family has at least four ligands, two receptors, and a binding protein. Its well-known role in the hypothalamic-pituitary-adrenal (HPA) axis is only one of many. The expression of CRH and its related peptides is widespread in peripheral tissue, with important functions in the immune system, energy metabolism, and female reproduction. For example, CRH is involved in the implantation of fertilized ova and in maternal tolerance to the fetus. An apparently unique adaptation has evolved in anthropoid primates: placental expression of CRH. Placental CRH stimulates the fetal adrenal zone, an adrenal structure unique to primates, to produce dehydroepiandrosterone sulfate (DHEAS), which is converted to estrogen by the placenta. Cortisol induced from the fetal and maternal adrenal glands by placental CRH induces further placental CRH expression, forming a positive feedback system that results in increasing placental production of estrogen. In humans, abnormally high placental expression of CRH is associated with pregnancy complications (e.g., preterm labor, intrauterine growth restriction (IUGR), and preeclampsia). Within anthropoid primates, there are at least two patterns of placental CRH expression over gestation: monkeys differ from great apes (and humans) by having a midgestational peak in CRH expression. The functional significance of these differences between monkeys and apes is not yet understood, but it supports the hypothesis that placental CRH performs multiple roles during gestation. A clearer understanding of the diversity of patterns of placental CRH expression among anthropoid primates would aid our understanding of its role in human pregnancy. Am. J. Hum. Biol. 18:431,447, 2006. © 2006 Wiley-Liss, Inc. [source]

ORIGINAL ARTICLE: Syngeneic Immune-Dependent Abortions in Mice Suggest Paternal Alloantigen-Independent Mechanisms

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2008
Jean A. Kundert
Problem, Recurrent immune-associated miscarriages in humans are thought to result from maternal immune responses to paternal alloantigens. We investigated the role of paternal alloantigens in a mouse model of immune-dependent abortion. Method of study, Sib-crosses of C57Bl/6J (haplotype b/b) mice heterozygous for a targeted hypomorphic allele of the tbp gene (tbp,,/+) resulted in selective mid-gestational abortion of 88% of the tbp,,/,, fetuses. In dams lacking mature lymphocytes (rag1,/,), nearly all tbp,,/,, fetuses survived to birth, indicating abortions were immune-dependent. Allogeneic pregnancies bearing tbp,,/,, fetuses were established by either hybridizing the paternal lineage to BALB/cJ (haplotype d/d) and mating hybrid tbp,,/+ sires to haplotype b/b tbp,,/+ C57Bl/6J dams, or by transfer of haplotype b/b zygotes from tbp,,/+ × tbp,,/+ matings into pseudopregnant wild-type CByD2F1/J dams (haplotype d/d). Results, Neither hemizygous paternal allogeneic loci nor homozygous allogeneic loci, including a haplotype-mismatched major histocompatibility complex (MHC), increased abortion frequencies. Conclusion, Results suggested that mechanisms for maternal tolerance of paternal alloantigens, including mismatched MHC antigens, were intact in these pregnancies, yet maternal immune-dependent paternal antigen-independent abortion of mutants occurred. These data indicate that, in some cases of immune-mediated abortions, the presence of paternal alloantigens can be coincidental and superfluous to the compromising rejection response. [source]

1141424444 Detection of a2V-ATPase in T regulatory cells of women with recurrent spontaneous abortions or implantation failures

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2006
EI Ntrivalas
Problem:, T regulatory cells (Tregs) have recently been shown to play a critical role in maternal tolerance to the fetus. Tregs are decreased in women with recurrent miscarriages. a2V-ATPase (previously referred to as Regeneration and Tolerance Factor) is expressed in activated lymphocytes and plays a role in immune regulation. The aim of this study was to investigate the expression of a2V-ATPase on CD4+/CD25bright Tregs. Method of Study:, Whole blood from women with RSA or implantation failures was reacted with anti-CD4 and anti-CD25 mAbs for the identification of CD4+/CD25bright and CD4+/CD25neg T cells by flow cytometric analysis. Subsequently, these two T-cell populations were analyzed for the expression of a2V-ATPase using PE-conjugated 2C1 mAb (specific for the membrane portion of a2V-ATPase). These two cell populations were also analyzed for the expression of CD71, CD62L, CD45RO and CD58 (Treg markers). Results:, a2V-ATPase was more highly expressed on CD4+/CD25bright Tregs (22.8 ± 16.4%) than on CD4+/CD25neg T cells (2.4 ± 3.8%) in women with RSA (P < 0.0001). Additionally, a2V-ATPase was more highly expressed on CD4+/CD25bright Tregs (18.0 ± 18.2%) than on CD4+/CD25neg T cells (1.5 ± 1.4%) in women with implantation failures (P < 0.0001). a2V-ATPase expression also coincided with the expression of CD71, CD62L, CD45RO and CD58 in Tregs, as opposed to the conventional CD4+/CD25neg T cells. Conclusions:, The expression of a2V-ATPase in Tregs of women with RSA or implantation failures is a novel finding and suggests that this vacuolar ATPase plays an important role in suppression. a2V-ATPase may be a unique molecule in the identification of Tregs among peripheral blood lymphocytes and may also explain the tolerogenic activity of these cells. [source]

Reproductive Functions of Corticotropin-Releasing Hormone.

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2004
Potential Clinical Utility of Antalarmins (CRH Receptor Type 1 Antagonists), Research
Background:, The hypothalamic-pituitary-adrenal (HPA) axis exerts a complex, mostly inhibitory, effect on the female reproductive system. In addition, the principal regulator of this axis, the hypothalamic neuropeptide corticotropin-releasing hormone (CRH) and its receptors have been identified in most female reproductive tissues, including the ovary, uterus, and placenta. Furthermore, CRH is secreted in peripheral inflammatory sites where it exerts strong inflammatory actions. Antalarmins (CRH receptor type 1 antagonists) have been used to elucidate the roles of CRH in stress, inflammation and reproduction. Method of study:, We review existing data on the effects of CRH in the female reproductive system. Results:, Ovarian CRH participates in female sex steroid production, follicular maturation, ovulation and luteolysis. Uterine CRH participates in decidualization, implantation, and early maternal tolerance. Placental CRH participates in the physiology of pregnancy and the onset of parturition. Circulating placental CRH is secreted mostly during the latter half of pregnancy and is responsible for the concurrently increasing physiologic hypercortisolism of this period. After labor and delivery, this hypercortisolism is ensued by a transient suppression of hypothalamic CRH secretion, which may explain the postpartum blues and depression and the increased autoimmune manifestations depression of period, the postpartum period. Conclusions:, These data show that CRH is present in female reproductive tissues, and is regulating key reproductive functions with an inflammatory component, such as ovulation, luteolysis, implantation, and parturition. [source]