scholarly journals Gene editing to investigate the role of conceptus factors in the establishment of pregnancy in the pig

Reproduction ◽  
2021 ◽  
Vol 161 (4) ◽  
pp. R79-R88
Author(s):  
Rodney D Geisert ◽  
Ashley E Meyer ◽  
Caroline A Pfeiffer ◽  
Destiny N Johns ◽  
Kiho Lee ◽  
...  
Keyword(s):  
Immune System ◽  
Growth And Development ◽  
Gene Editing ◽  
Biological Pathways ◽  
Loss Of Function ◽  
Trophoblast Differentiation ◽  
Maternal Immune System ◽  
Conceptus Development ◽  
Blastocyst Hatching

Development of viviparity in mammals requires that the placenta evolves as an intermediate interface between the fetus and maternal uterus. In addition to the retention of the fetus and secretion of nutrients to support growth and development to term, it is essential that viviparous species modify or inhibit the maternal immune system from recognizing the semi-allogeneic fetus. Following blastocyst hatching from its zona pellucida, trophoblast differentiation provides the initial communication to the maternal endometrium to regulate maintenance of progesterone production from the corpus luteum and biological pathways in uterine and conceptus development necessary in the establishment and maintenance of pregnancy. Many conceptus factors have been proposed to serve in the establishment and maintenance of pregnancy. CRISPR-Cas9 gene-editing technology provides a specific and efficient method to generate animal models to perform loss-of-function studies to investigate the role of specific conceptus factors. The utilization of CRISPR-Cas9 gene editing has provided a direct approach to investigate the specific role of conceptus factors in the development and establishment of pregnancy in the pig. This technology has helped address a number of questions concerning peri-implantation development and has altered our understanding of maternal recognition and maintenance of pregnancy in the pig.

scholarly journals Role of Human Leukocyte Antigens at the Feto-Maternal Interface in Normal and Pathological Pregnancy: An Update

2020 ◽  
Vol 21 (13) ◽  
pp. 4756
Author(s):  
Chiara Tersigni ◽  
Federica Meli ◽  
Caterina Neri ◽  
Azzurra Iacoangeli ◽  
Rita Franco ◽  
...  
Keyword(s):  
Immune System ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Immune Recognition ◽  
Protective Mechanisms ◽  
Maternal Immune System ◽  
Hla Class I Molecules ◽  
Classical Pattern ◽  
Hla Molecules

The successful maternal tolerance of the semi-allogeneic fetus provides an apparent immunologic paradox. Indeed, deep invasion of placental trophoblast cells into maternal uterine tissue and the following growth of the fetus have to be tolerated by a pregnant woman’s immune system. Among the various possible protective mechanisms that may be involved in human pregnancy, the expression of a non-classical pattern of human leukocyte antigen (HLA) class I molecules and the complete lack of expression of HLA class II molecules in placental tissues seem to be the most relevant mechanisms of fetal escape from maternal immune recognition. The importance of HLA molecules in fetal toleration by the maternal immune system is highlighted by pregnancy complications occurring in cases of abnormal HLA molecule expression at the maternal–fetal interface. In this review, we summarize evidences about the role of placental HLA molecules in normal and pathological pregnancies.

scholarly journals The Role of Zinc and Zinc Homeostasis in Macrophage Function

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Hong Gao ◽  
Wei Dai ◽  
Lu Zhao ◽  
Junxia Min ◽  
Fudi Wang
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Growth And Development ◽  
Innate Immune ◽  
Zinc Homeostasis ◽  
Zinc Transporters ◽  
Essential Trace Element ◽  
Macrophage Function ◽  
Living Organisms

Zinc has long been recognized as an essential trace element, playing roles in the growth and development of all living organisms. In recent decades, zinc homeostasis was also found to be important for the innate immune system, especially for maintaining the function of macrophages. It is now generally accepted that dysregulated zinc homeostasis in macrophages causes impaired phagocytosis and an abnormal inflammatory response. However, many questions remain with respect to the mechanisms that underlie these processes, particularly at the cellular and molecular levels. Here, we review our current understanding of the roles that zinc and zinc transporters play in regulating macrophage function.

scholarly journals Evidence for Maternal-Fetal Genotype Incompatibility as a Risk Factor for Schizophrenia

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Christina G. S. Palmer
Keyword(s):  
Risk Factor ◽  
Immune System ◽  
Data Analysis ◽  
Prenatal Environment ◽  
Analysis Techniques ◽  
Maternal Immune System ◽  
Study Designs ◽  
Schizophrenia Susceptibility ◽  
Fetal Genotype

Prenatal/obstetric complications are implicated in schizophrenia susceptibility. Some complications may arise from maternal-fetal genotype incompatibility, a term used to describe maternal-fetal genotype combinations that produce an adverse prenatal environment. A review of maternal-fetal genotype incompatibility studies suggests that schizophrenia susceptibility is increased by maternal-fetal genotype combinations at theRHDandHLA-Bloci. Maternal-fetal genotype combinations at these loci are hypothesized to have an effect on the maternal immune system during pregnancy which can affect fetal neurodevelopment and increase schizophrenia susceptibility. This article reviews maternal-fetal genotype incompatibility studies and schizophrenia and discusses the hypothesized biological role of these ‘‘incompatibility genes’’. It concludes that research is needed to further elucidate the role ofRHDandHLA-Bmaternal-fetal genotype incompatibility in schizophrenia and to identify other genes that produce an adverse prenatal environment through a maternal-fetal genotype incompatibility mechanism. Efforts to develop more sophisticated study designs and data analysis techniques for modeling maternal-fetal genotype incompatibility effects are warranted.

scholarly journals The Role of Progesterone in Feto-Maternal Immunological Cross Talk

2018 ◽  
Vol 27 (4) ◽  
pp. 301-307 ◽  
Author(s):  
Julia Szekeres-Bartho
Keyword(s):  
T Cells ◽  
Immune System ◽  
Nk Cells ◽  
Hla Antigens ◽  
Γδ T Cells ◽  
Normal Pregnancy ◽  
Maternal Immune System ◽  
Immunological Recognition ◽  
Immunological Relationship

This review aims to provide a brief historical overview of the feto-maternal immunological relationship, which profoundly influences the outcome of pregnancy. The initial question posed in the 1950s by Medawar [Symp Soc Exp Biol. 1953; 7: 320–338] was based on the assumption that the maternal immune system recognizes the fetus as an allograft. Indeed, based on the association between HLA-matching and spontaneous miscarriage, it became obvious that immunological recognition of pregnancy is required for a successful gestation. The restricted expression of polymorphic HLA antigens on the trophoblast, together with the presence of nonpolymorphic MHC products, excludes recognition by both T and NK cells of trophoblast-presented antigens; however, γδ T cells, which constitute the majority of decidual T cells, are likely candidates. Indeed, a high number of activated, progesterone receptor-expressing γδ T cells are present in the peripheral blood of healthy pregnant women and, in the presence of progesterone, these cells secrete an immunomodulatory protein called progesterone-induced blocking factor (PIBF). As early as in the peri-implantation period, the embryo communicates with the maternal immune system via PIBF containing extracellular vesicles. PIBF contributes to the dominance of Th2-type reactivity which characterizes normal pregnancy by inducing increased production of Th2 cytokines. The high expression of this molecule in the decidua might be one of the reasons for the low cytotoxic activity of decidual NK cells.

scholarly journals Ablation of conceptus PTGS2 expression does not alter early conceptus development and establishment of pregnancy in the pig†

2019 ◽  
Vol 102 (2) ◽  
pp. 475-488
Author(s):  
Caroline A Pfeiffer ◽  
Ashley E Meyer ◽  
Kelsey E Brooks ◽  
Paula R Chen ◽  
Jessica Milano-Foster ◽  
...  
Keyword(s):  
Early Development ◽  
Culture Media ◽  
Interleukin 1 ◽  
Corpora Lutea ◽  
Interleukin 1 Beta ◽  
Loss Of Function ◽  
Wild Type ◽  
Conceptus Development ◽  
Prostaglandin Endoperoxide Synthase

Abstract Pig conceptuses secrete estrogens (E2), interleukin 1 beta 2 (IL1B2), and prostaglandins (PGs) during the period of rapid trophoblast elongation and establishment of pregnancy. Previous studies established that IL1B2 is essential for rapid conceptus elongation, whereas E2 is not essential for conceptus elongation or early maintenance of the corpora lutea. The objective of the present study was to determine if conceptus expression of prostaglandin-endoperoxide synthase 2 (PTGS2) and release of PG are important for early development and establishment of pregnancy. To understand the role of PTGS2 in conceptus elongation and pregnancy establishment, a loss-of-function study was conducted by editing PTGS2 using CRISPR/Cas9 technology. Wild-type (PTGS2+/+) and null (PTGS2−/−) fibroblast cells were used to create embryos through somatic cell nuclear transfer. Immunolocalization of PTGS2 and PG production was absent in cultured PTGS2−/− blastocysts on day 7. PTGS2+/+ and PTGS2−/− blastocysts were transferred into surrogate gilts, and the reproductive tracts were collected on either days 14, 17, or 35 of pregnancy. After flushing the uterus on days 14 and 17, filamentous conceptuses were cultured for 3 h to determine PG production. Conceptus release of total PG, prostaglandin F2⍺ (PGF2α), and PGE in culture media was lower with PTGS2−/− conceptuses compared to PTGS2+/+ conceptuses. However, the total PG, PGF2α, and PGE content in the uterine flushings was not different. PTGS2−/− conceptus surrogates allowed to continue pregnancy were maintained beyond 30 days of gestation. These results indicate that pig conceptus PTGS2 is not essential for early development and establishment of pregnancy in the pig.

scholarly journals The Role of Macrophages in Oocyte Donation Pregnancy: A Systematic Review

2020 ◽  
Vol 21 (3) ◽  
pp. 939 ◽  
Author(s):  
Xuezi Tian ◽  
Michael Eikmans ◽  
Marie-Louise van der Hoorn
Keyword(s):  
Systematic Review ◽  
Immune System ◽  
Pregnant Woman ◽  
Biological Effects ◽  
Oocyte Donation ◽  
Arterial Remodeling ◽  
Healthy Pregnancy ◽  
Maternal Immune System ◽  
Made In

The embryo of an oocyte donation (OD) pregnancy is completely allogeneic to the mother, which leads to a more serious challenge for the maternal immune system to tolerize the fetus. It is thought that macrophages are essential in maintaining a healthy pregnancy, by acting in immunomodulation and spiral arterial remodeling. OD pregnancies represent an interesting model to study complex immunologic interactions between the fetus and the pregnant woman since the embryo is totally allogeneic compared to the mother. Here, we describe a narrative review on the role of macrophages and pregnancy and a systematic review was performed on the role of macrophages in OD pregnancies. Searches were made in different databases and the titles and abstracts were evaluated by three independent authors. In total, four articles were included on OD pregnancies and macrophages. Among these articles, some findings are conflicting between studies, indicating that more research is needed in this area. From current research, we could identify that there are multiple subtypes of macrophages, having diverse biological effects, and that the ratio between subtypes is altered during gestation and in aberrant pregnancy. The study of macrophages’ phenotypes and their functions in OD pregnancies might be beneficial to better understand the maternal-fetal tolerance system.

scholarly journals Interferon and Toll-Like Receptor 7 Response in COVID-19: Implications of Topical Imiquimod for Prophylaxis and Treatment

Dermatology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Mindy D. Szeto ◽  
Jalal Maghfour ◽  
Torunn E. Sivesind ◽  
Jarett Anderson ◽  
Jadesola T. Olayinka ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Critical Role ◽  
Innate Immune ◽  
Current Evidence ◽  
Loss Of Function ◽  
Strong Immune Response ◽  
Topical Imiquimod ◽  
Pubmed Database

<b><i>Background:</i></b> The innate immune system is recognized as an essential aspect of COVID-19 pathogenesis. Toll-like receptors (TLRs) are important in inducing antiviral response, triggering downstream production of interferons (IFNs). Certain loss-of-function variants in TLR7 are associated with increased COVID-19 disease severity, and imiquimod (ImiQ) is known to have immunomodulating effects as an agonist of TLR7. Given that topical imiquimod (topImiQ) is indicated for various dermatologic conditions, it is necessary for dermatologists to understand the interplay between innate immunity mechanisms and the potential role of ImiQ in COVID-19, with a particular focus on TLR7. <b><i>Summary:</i></b> Our objective was to survey recent peer-reviewed scientific literature in the PubMed database, examine relevant evidence, and elucidate the relationships between IFNs, TLR7, the innate immune system, and topImiQ in the context of COVID-19. Despite limited studies on this topic, current evidence supports the critical role of TLRs in mounting a strong immune response against COVID-19. Of particular interest to dermatologists, topImiQ can result in systemic upregulation of the immune system via activation of TLR7. <b><i>Key Message:</i></b> Given the role of TLR7 in the systemic activation of the immune system, ImiQ, as a ligand of the TLR7 receptor, may have potential therapeutic benefit as a topical immunomodulatory treatment for COVID-19.

scholarly journals Critical Role of the Maternal Immune System in the Pathogenesis of Autism Spectrum Disorder

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 557
Author(s):  
Davide Ravaccia ◽  
Taravat Ghafourian
Keyword(s):  
Immune System ◽  
Critical Role ◽  
Epidemiological Studies ◽  
Autism Spectrum ◽  
Therapeutic Interventions ◽  
Maternal Immune Activation ◽  
Maternal Immune System ◽  
Clinical Presentations ◽  
Spectrum Disorders

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterised by impairments in communication, social interaction, and the presence of restrictive and repetitive behaviours. Over the past decade, most of the research in ASD has focused on the contribution of genetics, with the identification of a variety of different genes and mutations. However, the vast heterogeneity in clinical presentations associated with this disorder suggests that environmental factors may be involved, acting as a “second hit” in already genetically susceptible individuals. To this regard, emerging evidence points towards a role for maternal immune system dysfunctions. This literature review considered evidence from epidemiological studies and aimed to discuss the pathological relevance of the maternal immune system in ASD by looking at the proposed mechanisms by which it alters the prenatal environment. In particular, this review focuses on the effects of maternal immune activation (MIA) by looking at foetal brain-reactive antibodies, cytokines and the microbiome. Despite the arguments presented here that strongly implicate MIA in the pathophysiology of ASD, further research is needed to fully understand the precise mechanisms by which they alter brain structure and behaviour. Overall, this review has not only shown the importance of the maternal immune system as a risk factor for ASD, but more importantly, has highlighted new promising pathways to target for the discovery of novel therapeutic interventions for the treatment of such a life-changing disorder.

Pregnancy Immunogenetics and Genomics: Implications for Pregnancy-Related Complications and Autoimmune Disease

2019 ◽  
Vol 20 (1) ◽  
pp. 73-97 ◽  
Author(s):  
Hing-Yuen Yeung ◽  
Calliope A. Dendrou
Keyword(s):  
Genetic Variation ◽  
Immune System ◽  
Growth And Development ◽  
System Function ◽  
Uterine Tissue ◽  
Successful Pregnancy ◽  
Immune Systems ◽  
Immune System Function ◽  
Maternal Immune System ◽  
The Impact

Pregnancy presents a singular physiological scenario during which the maternal immune system must accommodate the semiallogeneic fetus. Fluctuations between pro- and anti-inflammatory states are required throughout gestation to facilitate uterine tissue remodeling, fetal growth and development, and finally birth. Tolerance for the fetus must be established and maintained without fundamentally compromising the maternal immune system function, so that both the mother and fetus are protected from foreign insults. Here, we review our current understanding of how genetic variation at both maternal and fetal loci affects implantation and placenta formation, thereby determining the likelihood of a successful pregnancy outcome or the development of pregnancy-related complications. We also consider the impact of pregnancy on both the maternal and fetal systemic immune systems and the related implications for modulating ongoing autoimmune diseases and triggering their development.

scholarly journals The Role of PPARs in Placental Immunology: A Systematic Review of the Literature

PPAR Research ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Stefan Hutter ◽  
Julia Knabl ◽  
Ulrich Andergassen ◽  
Udo Jeschke
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Adaptive Immune System ◽  
Trophoblast Invasion ◽  
Peroxisome Proliferator ◽  
Maternal Immune System ◽  
Associated Conditions ◽  
Peroxisome Proliferator Activated Receptors ◽  
B And T Lymphocytes

Pregnancy is a state of immunotolerance, and pregnancy outcome is strongly linked to the correct activation and balancing of the maternal immune system. Besides abortion as possible result of improper early pregnancy development, other pregnancy associated conditions like preeclampsia (PE), intrauterine growth retardation (IUGR), preterm labour, or gestational diabetes mellitus (GDM) are linked to immunologic overactivation and dysregulation. Both the innate and the adaptive immune system, and therefore B and T lymphocytes, natural killer cells (NK), macrophages and dendritic cells (DCs) are all involved in trophoblast invasion, pregnancy maintenance, and development of pregnancy disorders. Peroxisome proliferator activated receptors (PPARs) are nuclear transcription factors with three known isotypes: PPAR, PPARβ/δ, and PPARγ. They are expressed in most human organs and their function extends from regulating metabolism, homeostasis, and carcinogenesis to immune response. In the recent years, PPARs have been identified in most reproductive tissues and in all lines of immune cells. Only in few cases, the role of PPARs in reproductive immunology has been elucidated though the role of PPARs in immune answer and immunotolerance is evident. Within this paper we would like to give an update on today’s knowledge about PPARs and immune cells in reproduction and highlight interesting interferences in regard of future therapeutic targets.

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