85 research outputs found

    Pregnancy initiation in the rhesus macaque: Towards functional manipulation of the maternal-fetal interface

    Get PDF
    Nonhuman primates provide an important opportunity to define the mechanisms that contribute to the success of early pregnancy. We have focused for several years now on defining the expression of novel placental major histocompatibility complex (MHC) class I molecules. In parallel, we have used reagents against human immune cell markers to characterize the leukocyte population in the decidua and have demonstrated dynamic changes in these cell populations during the first 5 weeks of gestation. The challenge is to identify the possible role(s) of placental MHC class I in modifying/directing the maternal endometrial or systemic immune system in the post-implantation period. Foremost among the challenges is the difficulty in modifying placental function. In the instance of trophoblast surface proteins, passive immunization studies are feasible, although limitations include the empirical nature of this approach, as well as the inability to modify intracellular function. We have shown that using lentiviral vectors to effect preimplantation gene transfer for transgene expression in the placenta is not only feasible, but of good efficiency. In addition to transgene overexpression, robust approaches for knocking down/knocking out placental gene expression are essential. Recent developments in RNA interference approaches may allow "transient knockout" experiments. While the rhesus monkey has been our model of choice, currently there are limitations in the number of available female rhesus monkeys of reproductive age for research in early pregnancy. It is critical that the technologies for advanced study move forward in other species. The baboon has been used significantly in reproductive tract biology and early pregnancy research and important models have been developed for manipulation of the maternal-fetal interface. Additional characterization of other species, such as the cynomolgus and African green (vervet) monkey is critical. Given the limitations on antigen recognition when using human reagents, we also propose that the development of panels of primate-specific anti-leukocyte antibodies is essential for moving forward nonhuman primate reproductive research

    Hofbauer Cells: Their Role in Healthy and Complicated Pregnancy

    Get PDF
    Hofbauer cells are placental villous macrophages of fetal origin that are present throughout pregnancy. Although Hofbauer cell populations are antigenically and morphologically heterogeneous, their epigenetic, antigenic, and functional profiles most closely resemble alternatively activated macrophages or what are referred to as M2a, M2b, M2c, and M2d polarity subtypes. Consistent with an M2-like profile, these cells play an important role in placental development including vasculogenesis and angiogenesis. During placental inflammation Hofbauer cells may produce pro-inflammatory cytokines or mediators that damage the villous cell barrier, and induce fibrotic responses within the villi as a continuum of chronic inflammation. However, to date, there is no evidence that Hofbauer cells become classically activated or adopt an M1 polarity phenotype that is able to kill microbes. To the contrary, their predominant M2 like qualities may be why these cells are ineffective in controlling most TORCH infections. Moreover, Hofbauer cells may contribute to vertical transmission of various pathogens to the fetus since they can harbor live virus and serve as reservoirs within the placenta. The goal of this review is to summarize what is currently known about the role of Hofbauer cells in normal and complicated pregnancies that involve immunologic disorders, inflammation, and/or infection

    Control of maternal Zika virus infection during pregnancy is associated with lower antibody titers in a macaque model

    Get PDF
    IntroductionZika virus (ZIKV) infection during pregnancy results in a spectrum of birth defects and neurodevelopmental deficits in prenatally exposed infants, with no clear understanding of why some pregnancies are more severely affected. Differential control of maternal ZIKV infection may explain the spectrum of adverse outcomes.MethodsHere, we investigated whether the magnitude and breadth of the maternal ZIKV-specific antibody response is associated with better virologic control using a rhesus macaque model of prenatal ZIKV infection. We inoculated 18 dams with an Asian-lineage ZIKV isolate (PRVABC59) at 30-45 gestational days. Plasma vRNA and infectious virus kinetics were determined over the course of pregnancy, as well as vRNA burden in the maternal-fetal interface (MFI) at delivery. Binding and neutralizing antibody assays were performed to determine the magnitude of the ZIKV-specific IgM and IgG antibody responses throughout pregnancy, along with peptide microarray assays to define the breadth of linear ZIKV epitopes recognized.ResultsDams with better virologic control (n= 9) cleared detectable infectious virus and vRNA from the plasma by 7 days post-infection (DPI) and had a lower vRNA burden in the MFI at delivery. In comparison, dams with worse virologic control (n= 9) still cleared detectable infectious virus from the plasma by 7 DPI but had vRNA that persisted longer, and had higher vRNA burden in the MFI at delivery. The magnitudes of the ZIKV-specific antibody responses were significantly lower in the dams with better virologic control, suggesting that higher antibody titers are not associated with better control of ZIKV infection. Additionally, the breadth of the ZIKV linear epitopes recognized did not differ between the dams with better and worse control of ZIKV infection.DiscussionThus, the magnitude and breadth of the maternal antibody responses do not seem to impact maternal virologic control. This may be because control of maternal infection is determined in the first 7 DPI, when detectable infectious virus is present and before robust antibody responses are generated. However, the presence of higher ZIKV-specific antibody titers in dams with worse virologic control suggests that these could be used as a biomarker of poor maternal control of infection and should be explored further

    IFPA meeting 2018 workshop report II: Abnormally invasive placenta; inflammation and infection; preeclampsia; gestational trophoblastic disease and drug delivery

    Get PDF
    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2018 there were nine themed workshops, five of which are summarised in this report. These workshops discussed new perspectives and knowledge in the following areas of research: 1) preeclampsia; 2) abnormally invasive placenta; 3) placental infection; 4) gestational trophoblastic disease; 4) drug delivery to treat placental dysfunction

    Regulation of Serum and Ovarian Relaxin Levels and Corpus Luteum Function During the Second Half of Pregnancy in the Rat (Ovary, Birth, Gestation)

    No full text
    153 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1984.The studies presented in this thesis were conducted to investigate the regulation of relaxin synthesis and secretion by the ovary from days 12 to 20 of pregnancy in the rat (Phase I). Initial immunocytochemical studies utilizing a specific rabbit anti-rat relaxin serum demonstrated that the cells of the corpus luteum (CL) are the only source of relaxin in the pregnant rat. The role of the conceptus in regulating relaxin synthesis and secretion was examined by investigating the effects of conceptus number on serum and ovarian relaxin levels, as well as on serum progesterone (P4) levels and CL weights. A direct relationship between the number of conceptuses and the rate and/or degree of increase in these parameters during Phase I was demonstrated. Additionally, it was shown that the placenta but not the fetus is responsible for maintaining elevated relaxin levels. The influence of the maternal pituitary on CL function during Phase I was then investigated. While rats bearing one conceptus had markedly reduced serum and luteal relaxin levels, serum P4 levels, and CL weights from days 14 to 20 compared to rats bearing a full complement of > 8 conceptuses, hypophysectomy at midpregnancy restored all these parameters except luteal relaxin content to levels similar to those seen in full complement-bearing rats. These results suggest that while the placenta maintains CL function during Phase I, the pituitary has a suppressive effect on the CL. This suppressive effect of the maternal pituitary was further investigated by determining the effects of hypophysectomy on CL function in rats with CL ectopically established under the kidney capsule (eCL) in the absence of the ovary. Consistent with results obtained in rats with intact ovaries, serum relaxin levels and CL weights were lower in eCL rats with 2 conceptuses than in those with > 5 conceptuses, but were significantly increased following hypophysectomy. Serum P4 levels also tended to follow the trends observed with serum relaxin levels. It was concluded that the nonluteal portion of the ovary does not mediate the suppressive effect of the pituitary on luteal function during Phase I in pregnant rats.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

    Decidual leukocytes respond to African lineage Zika virus infection with mild anti-inflammatory changes during acute infection in rhesus macaques

    No full text
    Zika virus (ZIKV) can be vertically transmitted during pregnancy resulting in a range of adverse pregnancy outcomes. The decidua is commonly found to be infected by ZIKV, yet the acute immune response to infection remains understudied in vivo. We hypothesized that in vivo African-lineage ZIKV infection induces a pro-inflammatory response in the decidua. To test this hypothesis, we evaluated the decidua in pregnant rhesus macaques within the first two weeks following infection with an African-lineage ZIKV and compared our findings to gestationally aged-matched controls. Decidual leukocytes were phenotypically evaluated using spectral flow cytometry, and cytokines and chemokines were measured in tissue homogenates from the decidua, placenta, and fetal membranes. The results of this study did not support our hypothesis. Although ZIKV RNA was detected in the decidual tissue samples from all ZIKV infected dams, phenotypic changes in decidual leukocytes and differences in cytokine profiles suggest that the decidua undergoes mild anti-inflammatory changes in response to that infection. Our findings emphasize the immunological state of the gravid uterus as a relatively immune privileged site that prioritizes tolerance of the fetus over mounting a pro-inflammatory response to clear infection
    • …
    corecore