Advances in understanding the physiological mechanism of maternal immune tolerance to the embryo

The results of immunological studies, especially research conducted in the last decade, have shown that free (not bound to protein) progesterone molecules (fP₄) can block the ability of dendritic cells, monocytes and macrophages to present antigens to Th cells and thereby reduce maternal immune activity and increase the maternal tolerance to the semiallogenic embryo. Endocrine studies have shown that fP₄ in the female reproductive organs are transferred at high concentrations into the arterial blood that supplies the oviduct and uterus due to the special adaptations of the blood circulation and lymph flow. Here, the authors present the results of numerous studies documenting their thesis that an important element of maternal tolerance of the semiallogenic embryo in the uterus is conditioned by the close interaction of two processes that occur in the reproductive organs: (1) the local decrease of maternal immune system activity, in which the ability of dendritic cells, macrophages and monocytes to present embryonic antigens to Th cells is blocked by fP₄; and (2) the proper function of the system governing the local retrograde and destination transfer of hormones, which increases the concentration of fP₄ that are able to immediately bind to their receptors in dendritic cells and in the monocytes and macrophages present in the blood supplying the oviduct and uterus. The authors believe that the local interaction of the immune and endocrine systems in the female reproductive tract reduces local maternal immunoreactivity and thus fulfils a critical physiological role; this mechanism protects the embryo but does not change the general immunological resistance of the mother.     

Dynamics of maternal and paternal effects on embryo and seed development in wild radish (Raphanus sativus)

Background and Aims

Variability in embryo development can influence the rate of seed maturation and seed size, which may have an impact on offspring fitness. While it is expected that embryo development will be under maternal control, more controversial hypotheses suggest that the pollen donor and the embryo itself may influence development. These latter possibilities are, however, poorly studied. Characteristics of 10-d-old embryos and seeds of wild radish (Raphanus sativus) were examined to address: (a) the effects of maternal plant and pollen donor on development; (b) the effects of earlier reproductive events (pollen tube growth and fertilization) on embryos and seeds, and the influence of embryo size on mature seed mass; (c) the effect of water stress on embryos and seeds; (d) the effect of stress on correlations of embryo and seed characteristics with earlier and later reproductive events and stages; and (e) changes in maternal and paternal effects on embryo and seed characteristics during development.

Methods

Eight maternal plants (two each from four families) and four pollen donors were crossed and developing gynoecia were collected at 10 d post-pollination. Half of the maternal plants experienced water stress. Characteristics of embryos and seeds were summarized and also compared with earlier and later developmental stages.

Key Results

In addition to the expected effects of the maternal plants, all embryo characters differed among pollen donors. Paternal effects varied over time, suggesting that there are windows of opportunity for pollen donors to influence embryo development. Water-stress treatment altered embryo characteristics; embryos were smaller and less developed. In addition, correlations of embryo characteristics with earlier and later stages changed dramatically with water stress.

Conclusions

The expected maternal effects on embryo development were observed, but there was also evidence for an early paternal role. The relative effects of these controls may change over time. Thus, there may be times in development when selection on the maternal, paternal or embryo contributions to development are more and less likely.     

EMBRYO GROWTH AND SEED SIZE IN RAPHANUS SATIVUS: MATERNAL AND PATERNAL EFFECTS IN VIVO AND IN VITRO

Theories on the evolution of the angiosperm seed disagree as to the effects of different plant tissues on embryo growth. To examine the relative contributions of maternal and paternal genes on embryo growth, we conducted controlled crosses in the greenhouse with wild radish plants (Raphanus sativus), looked for maternal, paternal, and interaction effects on embryo development, and compared the performance of embryos within fruits and in embryo culture. Maternal plant identity affected fruit set, seeds per fruit, embryo developmental stage, and mean seed weight. In embryo culture, maternal effects were found for cotyledon size and embryo weight. Paternal effects were fewer or smaller in magnitude than maternal effects. The identity of the pollen donor affected embryo developmental stage and mean seed weight. In culture, paternal effects were detected for cotyledon size and embryo weight. Our results demonstrate that both maternal and paternal elements affect embryo growth. The fact that maternal effects are greater than paternal effects on embryo development in culture may result from cytoplasmic elements or maternal nuclear genes. Embryo performance in vivo compared to that in vitro varied among maternal plants. The interaction between an embryo and its endosperm and maternal tissues may be either positive or negative, depending upon the maternal plant and the embryo's developmental stage.     

The Armadillo Repeat Gene ZAK IXIK Promotes Arabidopsis Early Embryo and Endosperm Development through a Distinctive Gametophytic Maternal Effect

The proper balance of parental genomic contributions to the fertilized embryo and endosperm is essential for their normal growth and development. The characterization of many gametophytic maternal effect (GME) mutants affecting seed development indicates that there are certain classes of genes with a predominant maternal contribution. We present a detailed analysis of the GME mutant zak ixik (zix), which displays delayed and arrested growth at the earliest stages of embryo and endosperm development. ZIX encodes an Armadillo repeat (Arm) protein highly conserved across eukaryotes. Expression studies revealed that ZIX manifests a GME through preferential maternal expression in the early embryo and endosperm. This parent-of-origin–dependent expression is regulated by neither the histone and DNA methylation nor the DNA demethylation pathways known to regulate some other GME mutants. The ZIX protein is localized in the cytoplasm and nucleus of cells in reproductive tissues and actively dividing root zones. The maternal ZIX allele is required for the maternal expression of MINISEED3. Collectively, our results reveal a reproductive function of plant Arm proteins in promoting early seed growth, which is achieved through a distinct GME of ZIX that involves mechanisms for maternal allele-specific expression that are independent of the well-established pathways.     

Inheritance of some quantitative morphological characters in reciprocal hybrids of starred sturgeon <Emphasis Type="Italic">Acipenser stellatus</Emphasis>and beluga <Emphasis Type="Italic">A. huso</Emphasis> (Acipenseridae)

Some quantitative characters of three-summer old reciprocal hybrids of beluga Acipenser huso and starred sturgeon A. stellatus,as well as of juveniles of their parental species, are comparatively analyzed. The found maternal and paternal effects in manifestation of some characteristics in hybrids are considered in connection with elucidation of inheritance type of morphological characters in acipenserids. The paternal effect observed by some characters in hybrids beluga × starred sturgeon is explained by prevalence of dominant alleles in the genome of starred sturgeon in comparison with beluga. The maternal effect is elucidated by a few characteristics related to parameters of the head, first of all to the volume of the brain region of skull. Evidently, in this case, the matrocliny depends on the fact that information on the number of segments of embryo and their position is determined by the maternal organism during oogenesis.     

Cytokines in the oviparity/viviparity transition: evidence of the interleukin-1 system in a species with reproductive bimodality, the lizard Lacerta vivipara

Placental viviparity is a reproductive strategy usually attributed to mammals. However, it is also present in other vertebrate species, e.g. in Squamate reptiles. Although the immunological mechanisms that allow the survival of the semi-allogenic embryo in maternal tissues are still largely unknown, cytokines seem to play an important role in mammalian reproduction. Previous studies in our laboratory showed that interleukin-1 (IL-1), a cytokine associated with implantation in mice, is also expressed at the materno-fetal interface of placental viviparous Squamates. In this study, we used the model of Lacerta vivipara, which exhibits reproductive bimodality, that is, the coexistence of oviparous and viviparous populations. By means of immunohistochemistry and anti-human antibodies, we showed that uterine tissues of L. vivipara (seven oviparous and six viviparous animals) expressed the two IL-1 isoforms, IL-1alpha and IL-1beta, and the type I IL-1 receptor (IL-1R tI) both at the pre-ovulatory stage and during gestation, with no significant difference between oviparous and viviparous females. In L. vivipara, as in most oviparous Squamates, an important phase of embryonic development takes place in the mother's oviduct, before egg-laying. Moreover, although thinner than in oviparous females, an eggshell membrane persists throughout gestation in viviparous females also, which develop a very simple type of placenta. The data suggest that immunological mechanisms that allow the survival of the semi-allogenic embryo in maternal tissues are independent of the timing or intimacy of contact between maternal and fetal tissues.     

Integumentary embryony in CMS sunflower line

Formation of integumentary embryos has been revealed in the ovules of the VIR 116 CMS line of sunflower (Helianthus annuus L.) pollinated by H. occidentalis, a perennial wild sunflower species. These embryos are observed within 7–9 days after the pollination in embryo sacs, where the normal fertilization did not occur. The embryos develop from somatic cells of a maternal organism (an integument) and can be one of the reasons of a matroclinal inheritance in interspecies hybrids.     

Chief types of placental trophism]

An attempt is made to represent a theory on two types of placental throphism. The first type--nutrition is mainly performed at the expense of maternal proteins, which in the placental chorion undergo proteolysis with formation of polypeptides and amino acids; embryospecific proteins are formed in the liver of the embryo. This type is characteristic for the animals with epithelio-chorionic acid and partly with desmo-chorionic placentas. The second type is characterized by resorption of amino acids from the maternal organism, from the latter embryospecific proteins are synthesized in the chorion. Thus, placental nutrition is specific for man and animals with hemochorionic and, partly, with endothelio-chorionic placentas.     

Recurrent Implantation Failure-update overview on etiology,diagnosis, treatment and future directions

Recurrent implantation failure (RIF) refers to cases in which women have had three failed in vitro fertilization (IVF) attempts with good quality embryos. The definition should also take advanced maternal age and embryo stage into consideration. The failure of embryo implantation can be a consequence of uterine, male, or embryo factors, or the specific type of IVF protocol. These cases should be investigated to determine the most likely etiologies of the condition, as this is a complex problem with several variables. There are multiple risk factors for recurrent implantation failure including advanced maternal age, smoking status of both parents, elevated body mass index, and stress levels. Immunological factors such as cytokine levels and presence of specific autoantibodies should be examined, as well as any infectious organisms in the uterus leading to chronic endometritis. Uterine pathologies such as polyps and myomas as well as congenital anatomical anomalies should be ruled out. Sperm analysis, pre-implantation genetic screening and endometrial receptivity should be considered and evaluated, and IVF protocols should be tailored to specific patients or patient populations. Treatment approaches should be directed toward individual patient cases. In addition, we suggest considering a new initial step in approach to patients with RIF, individualized planned activities to activate the brain's reward system in attempt to improve immunological balance in the body.     

Zonula occludens-1 and E-cadherin are coordinately expressed in the mouse uterus with the initiation of implantation and decidualization

Two-way interactions between the blastocyst trophectoderm and the uterine luminal epithelium are essential for implantation. The key events of this process are cell-cell contact of trophectoderm cells with uterine luminal epithelial cells, controlled invasion of trophoblast cells through the luminal epithelium and the basement membrane, transformation of uterine stromal cells surrounding the blastocyst into decidual cells, and protection of the "semiallogenic" embryo from the mother's immunological responses. Because cell-cell contact between the trophectoderm epithelium and the luminal epithelium is essential for implantation, we investigated the expression of zonula occludens-1 (ZO-1) and E-cadherin, two molecules associated with epithelial cell junctions, in the mouse uterus during the periimplantation period. Preimplantation uterine epithelial cells express both ZO-1 and E-cadherin. With the initiation and progression of implantation, ZO-1 and E-cadherin are expressed in stromal cells of the primary decidual zone (PDZ). As trophoblast invasion progresses, these two molecules are expressed in stroma in advance of the invading trophoblast cells. These results suggest that expression of these adherence and tight junctions molecules in the PDZ serves to function as a permeability barrier to regulate access of immunologically competent maternal cells and/or molecules to the embryo and provide homotypic guidance of trophoblast cells in the endometrium.     

Investigating chorion softening of zebrafish embryos with a microrobotic force sensing system

The zebrafish is a model organism for addressing questions of vertebrate embryo development. In this paper, the softening phenomenon of the chorion envelope of zebrafish embryos at different developmental stages was mechanically quantitated by using a microrobotic force sensing system. The microrobotic system integrates a piezoelectric cellular force sensor to measure the required forces for penetrating the chorion envelope. Magnitude of penetration forces was found to decrease as an embryo develops. The results mechanically quantitate "chorion softening" in zebrafish embryos due to protease activities subtly modifying the chorion structure, providing an understanding of zebrafish embryo development.     

Ultrastructure of the oocyte and embryo of the calcified sponge,Petrobiona massiliana (Porifera,Calcarea)

Summary In the spongePetrobiona massiliana, a Calcarea related to pharetronid fossils, the oocyte and the embryo both receive an unusual amount of maternal nurse cells. Yolk granules are large and display a lamellar structure throughout the entire growth period, which allows them to be used as markers of the oocyte reserves. The cruciform cells (cellules en croix) of the embryo appear to degenerate at an early stage. These features are compared to those found in other Calcarea.     

Embryo nutrition in parthenogenetic viviparous aphids

Abstract The reproductive potential of aphids is well known and is the basis for their considerable economic importance. Reproductive output is ultimately fuelled by nutrients derived from the maternal haemolymph but mechanisms of embryo provisioning are poorly understood. Here, the morphological features of the reproductive system that have a critical role in nutrient transfer are reviewed, and the contribution of the symbiotic bacteria Buchnera to embryo nutrition is considered. In particular, the importance of the ovariole sheath as the selective barrier for nutrient exchange between the maternal haemolymph and the embryo tissue is highlighted, along with the division of the bacterial population into distinct embryo and maternal compartments. Three models are proposed to explain the relative contribution of the symbiotic compartments to embryo nutrition and the review concludes by highlighting experimental studies that have directly examined nutrient transfer from the maternal haemolymph to the developing embryos.     

The spontaneous lymphocyte transformation rate in newborn infants at risk]

The lymphocyte transformation test was performed in 32 risk newborns and 32 comparative persons (17 adults, 15 children). In the void controls without antigen addition the newborns had a significantly higher spontaneous blastic reaction than the control group. The phenomenon may be explained by lymphatic stem cells in the blood or an ontogenetically higher content of "embryonic tissue" respectively being present as unspecific stimulant or an immunological defence reaction against maternal immunoglobulins transmitted diaplacentally (formation of antigammaglobulin factors) or against maternal lymphocytes to prevent a "runt disease".     

Zinc transporter expression in zebrafish (Danio rerio) during development

Zinc is a micronutrient important in several biological processes including growth and development. We have limited knowledge on the impact of maternal zinc deficiency on zinc and zinc regulatory mechanisms in the developing embryo due to a lack of in vivo experimental models that allow us to directly study the effects of maternal zinc on embryonic development following implantation. To overcome this barrier, we have proposed to use zebrafish as a model organism to study the impact of zinc during development. The goal of the current study was to profile the mRNA expression of all the known zinc transporter genes in the zebrafish across embryonic and larval development and to quantify the embryonic zinc concentrations at these corresponding developmental time points. The SLC30A zinc transporter family (ZnT) and SLC39A family, Zir-,Irt-like protein (ZIP) zinc transporter proteins were profiled in zebrafish embryos at 0, 2, 6, 12, 24, 48 and 120 h post fertilization to capture expression patterns from a single cell through full development. We observed consistent embryonic zinc levels, but differential expression of several zinc transporters across development. These results suggest that zebrafish is an effective model organism to study the effects of zinc deficiency and further investigation is underway to identify possible molecular pathways that are dysregulated with maternal zinc deficiency.     

Defining life from death: Problems with the somatic integration definition of life

To determine when the life of a human organism begins, Mark T. Brown has developed the somatic integration definition of life. Derived from diagnostic criteria for human death, Brown’s account requires the presence of a life-regulation internal control system for an entity to be considered a living organism. According to Brown, the earliest point at which a developing human could satisfy this requirement is at the beginning of the fetal stage, and so the embryo is not regarded as a living human organism. This, Brown claims, has significant bioethical implications for both abortion and embryo experimentation. Here, we dispute the cogency of Brown’s derivation. Diagnostic criteria for death are used to determine when an organism irreversibly ceases functioning as an integrated whole, and may vary significantly depending on how developed the organism is. Brown’s definition is derived from a specific definition of death applicable to postnatal human beings, which is insufficient for generating a general definition for human organismal life. We have also examined the bioethical implications of Brown’s view, and have concluded that they are not as significant as he believes. Whether the embryo is classified as a human organism is of peripheral interest—a far more morally relevant question is whether the embryo is a biological individual with an identity that is capable of persisting during development.     

The Drosophila gap gene network is composed of two parallel toggle switches

Drosophila "gap" genes provide the first response to maternal gradients in the early fly embryo. Gap genes are expressed in a series of broad bands across the embryo during first hours of development. The gene network controlling the gap gene expression patterns includes inputs from maternal gradients and mutual repression between the gap genes themselves. In this study we propose a modular design for the gap gene network, involving two relatively independent network domains. The core of each network domain includes a toggle switch corresponding to a pair of mutually repressive gap genes, operated in space by maternal inputs. The toggle switches present in the gap network are evocative of the phage lambda switch, but they are operated positionally (in space) by the maternal gradients, so the synthesis rates for the competing components change along the embryo anterior-posterior axis. Dynamic model, constructed based on the proposed principle, with elements of fractional site occupancy, required 5-7 parameters to fit quantitative spatial expression data for gap gradients. The identified model solutions (parameter combinations) reproduced major dynamic features of the gap gradient system and explained gap expression in a variety of segmentation mutants.     

Modifications in major satellite methylation in the nucleus of a two-cell mouse embryo with respect to developmental conditions

A study was conducted of the degree of DNA methylation in the nucleus, in particular, of the major satellite in two-cell mouse embryos developing in the maternal organism, in standard culture medium M16, used for cultivating mouse embryos; and M2 media used for manipulating embryos in air. Two-cell embryo nuclei at 44–46 h after injections of chorionic hormone were investigated. The results are evidence for the dependence of the major satellite’s methylation level on the developmental conditions of embryos. The methylation level of the nuclear DNA was shown to increase with a deterioration of environmental conditions. It was reported that in the case of cultivation in M2 media unsuitable for long cultivation, the DNAís methylation level, the major satellite in particular, was higher compared to other embryo groups. Accordingly, not only a significant number of genes but also sequences of satellite DNA are involved in epigenetic regulation.