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Reproductive Immunology and Pregnancy 3.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (15 June 2023) | Viewed by 28368

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Guest Editor
Department of Biophysics, Physiology and Pathophysiology, Faculty of Health Sciences, Medical University of Warsaw, Chalubinskiego 5 (4th Floor), 02-004 Warsaw, Poland
Interests: inflammation; cytokine network; human placenta; stem cells in reproductive tissues; pathophysiology of diabetes
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Special Issue Information

Dear Colleagues,

Reproductive immunology refers to studies of the interrelationships between the immune and reproductive systems. The tremendous advances in reproductive immunology in the 21st century do not change the fact that the role of the immune system in reproduction remains unclear. In light of the latest research results, it appears that interaction rather than competition between the reproductive and immune systems enables the normal preservation of reproductive function. This interaction covers all stages: from the formation of female and male gametes through to fertilization, implantation, and placentation and from intrauterine development of the fetus to the delivery of a healthy newborn at term. Malfunctioning of the immune/reproductive interaction at any of these stages may result in predisposition to infertility or an abnormal pregnancy course.

It is notable that intensive study of the immunology of stem cells, which are abundantly present in the reproductive tissues (e.g., placenta, endometrium), has significantly increased knowledge in the field of reproductive immunology.

This Special Issue is dedicated to all aspects of reproductive immunology, including the immunology of pregnancy in health and disease. When considering your submission, please keep in mind that IJMS is a journal of molecular science. However, submissions of clinical studies that include biomolecular experiments or pathological research with case sample data are welcomed.

Following our previous successful editorial experience with this topic, we decided to continue this Special Issue in the third edition.

Prof. Dr. Dariusz Szukiewicz
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • gamete immunology
  • in vitro fertilization
  • infertility
  • immunocontraception
  • implantation
  • placentation
  • immunotolerance
  • reproductive immunology
  • inflammation
  • cytokine network
  • placenta-derived stem cells
  • endometriosis
  • immunopathology of pregnancy
  • sex hormones

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Published Papers (12 papers)

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Editorial

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6 pages, 603 KiB  
Editorial
Reproductive Immunology and Pregnancy 3.0
by Dariusz Szukiewicz
Int. J. Mol. Sci. 2023, 24(23), 16606; https://doi.org/10.3390/ijms242316606 - 22 Nov 2023
Cited by 1 | Viewed by 1068
Abstract
This Special Issue, the third dedicated to reproductive immunology and pregnancy, is another review of the latest trends in research topics in this field [...] Full article
(This article belongs to the Special Issue Reproductive Immunology and Pregnancy 3.0)
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Research

Jump to: Editorial, Review

13 pages, 725 KiB  
Article
Anti-β2-glycoprotein I/HLA-DR Antibody and Adverse Obstetric Outcomes
by Kenji Tanimura, Shigeru Saito, Sayaka Tsuda, Yosuke Ono, Hajime Ota, Shinichiro Wada, Masashi Deguchi, Mikiya Nakatsuka, Takeshi Nagamatsu, Tomoyuki Fujii, Gen Kobashi, Hisashi Arase and Hideto Yamada
Int. J. Mol. Sci. 2023, 24(13), 10958; https://doi.org/10.3390/ijms241310958 - 30 Jun 2023
Cited by 3 | Viewed by 1895
Abstract
Anti-β2-glycoprotein I/HLA-DR (anti-β2GPI/HLA-DR) antibody has been reported to be associated with antiphospholipid syndrome and recurrent pregnancy loss (RPL). We conducted a prospective multicenter cross-sectional study aimed at evaluating whether the anti-β2GPI/HLA-DR antibody is associated with adverse obstetric outcomes and RPL. From 2019 to [...] Read more.
Anti-β2-glycoprotein I/HLA-DR (anti-β2GPI/HLA-DR) antibody has been reported to be associated with antiphospholipid syndrome and recurrent pregnancy loss (RPL). We conducted a prospective multicenter cross-sectional study aimed at evaluating whether the anti-β2GPI/HLA-DR antibody is associated with adverse obstetric outcomes and RPL. From 2019 to 2021, serum anti-β2GPI/HLA-DR antibody levels (normal, <73.3 U) were measured in 462 women with RPL, 124 with fetal growth restriction (FGR), 138 with hypertensive disorders of pregnancy (HDP), 71 with preterm delivery before 34 gestational weeks (preterm delivery (PD) ≤ 34 GWs), and 488 control women who experienced normal delivery, by flow cytometry analysis. The adjusted odds ratios (aORs) of anti-β2GPI/HLA-DR antibody positivity for adverse obstetric outcomes and RPL were evaluated on the basis of comparisons between the control and each patient group, using multivariable logistic regression analysis. The following were the positivity rates for the anti-β2GPI/HLA-DR antibody in the patient and control groups: RPL, 16.9%; FGR, 15.3%; HDP, 17.4%; PD ≤ 34 GWs, 11.3%; and the control, 5.5%. It was demonstrated that anti-β2GPI/HLA-DR antibody positivity was a significant risk factor for RPL (aOR, 3.3 [95% confidence interval {CI} 1.9–5.6], p < 0.001), FGR (2.7 [1.3–5.3], p < 0.01), and HDP (2.7 [1.4–5.3], p < 0.01) although not for PD ≤ 34 GWs. For the first time, our study demonstrated that the anti-β2GPI/HLA-DR antibody is involved in the pathophysiology underlying FGR and HDP, as well as RPL. Full article
(This article belongs to the Special Issue Reproductive Immunology and Pregnancy 3.0)
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32 pages, 3866 KiB  
Article
Hepatic Global Transcriptomic Profiles of Holstein Cows According to Parity Reveal Age-Related Changes in Early Lactation
by Zhangrui Cheng, Conrad Ferris, Mark A. Crowe, Klaus L. Ingvartsen, Clément Grelet, Amélie Vanlierde, Leslie Foldager, Frank Becker, D. Claire Wathes and the GplusE Consortium
Int. J. Mol. Sci. 2023, 24(12), 9906; https://doi.org/10.3390/ijms24129906 - 8 Jun 2023
Cited by 2 | Viewed by 2032
Abstract
Cows can live for over 20 years, but their productive lifespan averages only around 3 years after first calving. Liver dysfunction can reduce lifespan by increasing the risk of metabolic and infectious disease. This study investigated the changes in hepatic global transcriptomic profiles [...] Read more.
Cows can live for over 20 years, but their productive lifespan averages only around 3 years after first calving. Liver dysfunction can reduce lifespan by increasing the risk of metabolic and infectious disease. This study investigated the changes in hepatic global transcriptomic profiles in early lactation Holstein cows in different lactations. Cows from five herds were grouped as primiparous (lactation number 1, PP, 534.7 ± 6.9 kg, n = 41), or multiparous with lactation numbers 2–3 (MP2–3, 634.5 ± 7.5 kg, n = 87) or 4–7 (MP4–7, 686.6 ± 11.4 kg, n = 40). Liver biopsies were collected at around 14 days after calving for RNA sequencing. Blood metabolites and milk yields were measured, and energy balance was calculated. There were extensive differences in hepatic gene expression between MP and PP cows, with 568 differentially expressed genes (DEGs) between MP2–3 and PP cows, and 719 DEGs between MP4–7 and PP cows, with downregulated DEGs predominating in MP cows. The differences between the two age groups of MP cows were moderate (82 DEGs). The gene expression differences suggested that MP cows had reduced immune functions compared with the PP cows. MP cows had increased gluconeogenesis but also evidence of impaired liver functionality. The MP cows had dysregulated protein synthesis and glycerophospholipid metabolism, and impaired genome and RNA stability and nutrient transport (22 differentially expressed solute carrier transporters). The genes associated with cell cycle arrest, apoptosis, and the production of antimicrobial peptides were upregulated. More surprisingly, evidence of hepatic inflammation leading to fibrosis was present in the primiparous cows as they started their first lactation. This study has therefore shown that the ageing process in the livers of dairy cows is accelerated by successive lactations and increasing milk yields. This was associated with evidence of metabolic and immune disorders together with hepatic dysfunction. These problems are likely to increase involuntary culling, thus reducing the average longevity in dairy herds. Full article
(This article belongs to the Special Issue Reproductive Immunology and Pregnancy 3.0)
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14 pages, 1234 KiB  
Article
Diagnostic Utility of TSSC3 and RB1 Immunohistochemistry in Hydatidiform Mole
by Wai Kit Chia, Pik Yuen Chia, Nor Haslinda Abdul Aziz, Salwati Shuib, Muaatamarulain Mustangin, Yoke Kqueen Cheah, Teck Yee Khong, Yin Ping Wong and Geok Chin Tan
Int. J. Mol. Sci. 2023, 24(11), 9656; https://doi.org/10.3390/ijms24119656 - 2 Jun 2023
Cited by 3 | Viewed by 1865
Abstract
The general notion of complete hydatidiform moles is that most of them consist entirely of paternal DNA; hence, they do not express p57, a paternally imprinted gene. This forms the basis for the diagnosis of hydatidiform moles. There are about 38 paternally imprinted [...] Read more.
The general notion of complete hydatidiform moles is that most of them consist entirely of paternal DNA; hence, they do not express p57, a paternally imprinted gene. This forms the basis for the diagnosis of hydatidiform moles. There are about 38 paternally imprinted genes. The aim of this study is to determine whether other paternally imprinted genes could also assist in the diagnostic approach of hydatidiform moles. This study comprised of 29 complete moles, 15 partial moles and 17 non-molar abortuses. Immunohistochemical study using the antibodies of paternal-imprinted (RB1, TSSC3 and DOG1) and maternal-imprinted (DNMT1 and GATA3) genes were performed. The antibodies’ immunoreactivity was evaluated on various placental cell types, namely cytotrophoblasts, syncytiotrophoblasts, villous stromal cells, extravillous intermediate trophoblasts and decidual cells. TSSC3 and RB1 expression were observed in all cases of partial moles and non-molar abortuses. In contrast, their expression in complete moles was identified in 31% (TSSC3) and 10.3% (RB1), respectively (p < 0.0001). DOG1 was consistently negative in all cell types in all cases. The expressions of maternally imprinted genes were seen in all cases, except for one case of complete mole where GATA3 was negative. Both TSSC3 and RB1 could serve as a useful adjunct to p57 for the discrimination of complete moles from partial moles and non-molar abortuses, especially in laboratories that lack comprehensive molecular service and in cases where p57 staining is equivocal. Full article
(This article belongs to the Special Issue Reproductive Immunology and Pregnancy 3.0)
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16 pages, 3469 KiB  
Article
CD8 and CD4 Positive NKT Subpopulations and Immune-Checkpoint Pathways in Early-Onset Preeclampsia and Healthy Pregnancy
by Matyas Meggyes, Timoteus Feik, David U. Nagy, Beata Polgar and Laszlo Szereday
Int. J. Mol. Sci. 2023, 24(2), 1390; https://doi.org/10.3390/ijms24021390 - 10 Jan 2023
Cited by 2 | Viewed by 2225
Abstract
Although many studies have investigated the clinical aspect of early-onset preeclampsia, our knowledge about the immunological consequences of improper placenta development is scarce. The maternal immunotolerance against the fetus is greatly influenced by the Th1 predominance developed by the mother’s immune system. Thirty-two [...] Read more.
Although many studies have investigated the clinical aspect of early-onset preeclampsia, our knowledge about the immunological consequences of improper placenta development is scarce. The maternal immunotolerance against the fetus is greatly influenced by the Th1 predominance developed by the mother’s immune system. Thirty-two early-onset preeclamptic and fifty-one healthy pregnant women with appropriately matched gestational age were involved in our study. Mononuclear cells were separated from peripheral venous blood and the frequency of CD8⁺, CD4⁺, double positive (DP), and double negative (DN) NKT cell subpopulations was determined using multicolor flow cytometry. Following the characterization, the expression levels of different immune checkpoint receptors and ligands were also defined. Soluble CD226 levels were quantified by ELISA. Novel and significant differences were revealed among the ratios of the investigated NKT subsets and in the expression patterns of PD-1, LAG-3, TIGIT and CD226 receptors. Further differences were determined in the expression of CD112, PD-1, LAG-3 and CD226 MFI values between the early-onset preeclamptic and the healthy pregnant groups. Our results suggest that the investigated NKT subpopulations act differently in the altered immune condition characteristic of early-onset preeclampsia and indicate that the different subsets may contribute to the compensation or maintenance of Th1 predominance. Full article
(This article belongs to the Special Issue Reproductive Immunology and Pregnancy 3.0)
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15 pages, 1476 KiB  
Article
Determination of the Predictive Roles and Potentially Pathogenic Antigen Epitopes of α-Enolase Related to the Development of Miscarriage in Females with Autoimmune Thyroiditis
by Jiahui Guo, Yihan Lu, Xiaoqing He, Jiashu Li, Chenling Fan, Hongmei Zhang, Weiping Teng, Zhongyan Shan and Jing Li
Int. J. Mol. Sci. 2023, 24(2), 1021; https://doi.org/10.3390/ijms24021021 - 5 Jan 2023
Viewed by 1639
Abstract
Autoimmune thyroiditis (AIT) is a common endocrine disease which causes a significantly increased risk of miscarriage. Our recent study has shown that the increased ENO1 autoantibody (ENO1Ab) expression in an experimental AIT mouse model was induced by thyroglobulin (Tg) immunization only. In this [...] Read more.
Autoimmune thyroiditis (AIT) is a common endocrine disease which causes a significantly increased risk of miscarriage. Our recent study has shown that the increased ENO1 autoantibody (ENO1Ab) expression in an experimental AIT mouse model was induced by thyroglobulin (Tg) immunization only. In this study, we explored the potential roles of ENO1Ab in miscarriage occurrence among AIT women, and the specific epitopes of ENO1 targeted by ENO1Ab. A total of 432 euthyroid pregnant participants were selected from the project of Subclinical Hypothyroid during Early Pregnancy, including 48 women with AIT and miscarriage, 96 with miscarriage but no AIT, 96 with AIT but no miscarriage, and 192 without either AIT or miscarriage. The enzyme-linked immunosorbent assay was used to determine the serum levels of total IgG against ENO1 and 18 predicted antigen epitopes of ENO1. The results showed that women with AIT and miscarriage had the highest serum levels of ENO1Ab compared to the other groups. Logistic regression analysis showed that the serum ENO1Ab was an independent risk factor for miscarriage, especially among AIT females. The serum level of total IgG against the predicted epitope peptide 6 (i.e., P6 and aa168-183) of ENO1 was significantly increased in women with AIT and miscarriage when compared with those of both the AIT non-miscarriage group and non-AIT miscarriage group. This pilot study suggests that serum ENO1Ab may have a fair predictive value for AIT-related miscarriage, and the autoantibody specific to P6 epitope may especially be more specifically related to this disorder. Full article
(This article belongs to the Special Issue Reproductive Immunology and Pregnancy 3.0)
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26 pages, 6419 KiB  
Article
Proportion of Concentrate in the Diet of Early Lactation Dairy Cows Has Contrasting Effects on Circulating Leukocyte Global Transcriptomic Profiles, Health and Fertility According to Parity
by Zhangrui Cheng, Danielle L. McLaughlin, Mark W. Little, Conrad Ferris, Mazdak Salavati, Klaus L. Ingvartsen, Mark A. Crowe, D. Claire Wathes and the GplusE Consortium
Int. J. Mol. Sci. 2023, 24(1), 39; https://doi.org/10.3390/ijms24010039 - 20 Dec 2022
Cited by 2 | Viewed by 2320
Abstract
The functionality of circulating leukocytes in dairy cows is suppressed after calving, with negative energy balance as a risk factor. Leukocyte transcriptomic profiles were compared separately in 44 multiparous (MP) and 18 primiparous (PP) Holstein–Friesian cows receiving diets differing in concentrate proportion to [...] Read more.
The functionality of circulating leukocytes in dairy cows is suppressed after calving, with negative energy balance as a risk factor. Leukocyte transcriptomic profiles were compared separately in 44 multiparous (MP) and 18 primiparous (PP) Holstein–Friesian cows receiving diets differing in concentrate proportion to test whether immune dysfunction could be mitigated by appropriate nutrition. After calving, cows were offered either (1) low concentrate (LC); (2) medium concentrate (MC) or (3) high concentrate (HC) diets with proportions of concentrate to grass silage of 30%:70%, 50%:50% and 70%:30%, respectively. Cow phenotype data collected included circulating metabolites, milk yield and health and fertility records. RNA sequencing of circulating leukocytes at 14 days in milk was performed. The HC diet improved energy balance in both age groups. There were more differentially expressed genes in PP than MP cows (460 vs. 173, HC vs. LC comparison) with few overlaps. The MP cows on the LC diet showed upregulation of the complement and coagulation cascade and innate immune defence mechanisms against pathogens and had a trend of more cases of mastitis and poorer fertility. In contrast, the PP cows on the HC diet showed greater immune responses based on both gene expression and phenotypic data and longer interval of calving to conception. The leukocytes of MP and PP cows therefore responded differentially to the diets between age, nutrient supply and immunity affecting their health and subsequent fertility. Full article
(This article belongs to the Special Issue Reproductive Immunology and Pregnancy 3.0)
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Review

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16 pages, 2319 KiB  
Review
New Potential Pharmacological Options for Endometriosis Associated Pain
by Laura García-Izquierdo, Pilar Marín-Sánchez, Pilar García-Peñarrubia and María Martínez-Esparza
Int. J. Mol. Sci. 2024, 25(13), 7068; https://doi.org/10.3390/ijms25137068 - 27 Jun 2024
Cited by 1 | Viewed by 1421
Abstract
Endometriosis is a chronic inflammatory disorder characterized by the abnormal growth of endometrial-like tissue outside the uterine cavity, affecting 10–15% of women of reproductive age. Pain is the most common symptom. Treatment options include surgery, which has limited effectiveness and high recurrence rates, [...] Read more.
Endometriosis is a chronic inflammatory disorder characterized by the abnormal growth of endometrial-like tissue outside the uterine cavity, affecting 10–15% of women of reproductive age. Pain is the most common symptom. Treatment options include surgery, which has limited effectiveness and high recurrence rates, and pharmacotherapy. Hormonal therapies, commonly used for symptom management, can have side effects and contraceptive outcomes, contributing to the infertility associated with endometriosis, with pain and lesions often reappearing after treatment cessation. Among its etiological factors, immunological and inflammatory dysregulation plays a significant role, representing an interesting target for developing new therapeutic strategies. This review critically analyzes recent studies to provide an updated synthesis of ongoing research into potential new pharmacotherapies focusing on lesion progression, pain relief, and improving quality of life. Immunotherapy, natural anti-inflammatory and antioxidant compounds and drug repurposing show promise in addressing the limitations of current treatments by targeting immunological factors, potentially offering non-invasive solutions for managing pain and infertility in endometriosis. Promising results have been obtained from in vitro and animal model studies, but clinical trials are still limited. More effort is needed to translate these findings into clinical practice to effectively reduce disease progression, alleviate pain symptoms and preserve the reproductive capacity, improving patients’ overall wellbeing. Full article
(This article belongs to the Special Issue Reproductive Immunology and Pregnancy 3.0)
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14 pages, 576 KiB  
Review
The Neglected Uterine NK Cells/Hamperl Cells/Endometrial Stromal Granular Cell, or K Cells: A Narrative Review from History through Histology and to Medical Education
by Lenka Lapides, Ivan Varga, Mária Csöbönyeiová, Martin Klein, Lada Pavlíková, Kristína Visnyaiová, Pavel Babál and Renáta Mikušová
Int. J. Mol. Sci. 2023, 24(16), 12693; https://doi.org/10.3390/ijms241612693 - 11 Aug 2023
Cited by 3 | Viewed by 2219
Abstract
Reproductive immunology is at the forefront of research interests, aiming to better understand the mechanisms of immune regulation during gestation. The relationship between the immune system and the implanting embryo is profound because the embryo is semi-allogenic but not targeted by the maternal [...] Read more.
Reproductive immunology is at the forefront of research interests, aiming to better understand the mechanisms of immune regulation during gestation. The relationship between the immune system and the implanting embryo is profound because the embryo is semi-allogenic but not targeted by the maternal immune system, as expected in graft-versus-host reactions. The most prominent cell population at the maternal–fetal interface is the population of uterine natural killer (uNK) cells. Uterine NK cells are two-faced immunologically active cells, bearing comparison with Janus, the ancient Roman god of beginnings and endings. Their first face can be seen as natural killer cells, namely lymphocytes, which are critical for host defense against viruses and tumors. Even though uNK cells contain cytolytic molecules, their cytotoxic effect is not applied to classical target cells in vivo, playing a permissive rather than a defensive role. Their second face is crucial in maintaining physiological gestation—uNK cells show critical immunomodulatory functions with the potential to control embryo implantation and trophoblast invasion, regulate placental vascular remodeling, and promote embryonic/fetal growth. Therefore, we believe that their current designation “natural killer cells” (the first “cytotoxic” Janus’s face) is misleading and inappropriate, considering their principal function is supporting and maintaining pregnancy. In this narrative review, we will focus on three lesser-known areas of knowledge about uNK cells. First, from the point of view of histology, we will comprehensively map the history of the discovery of these cells, as well as the current histological possibilities of their identification within the endometrium. To be brief, the discovery of uNK cells is generally attributed to Herwig Hamperl, one of the most influential and prominent representatives of German pathology in the 20th century, and his co-worker, Gisela Hellweg. Secondly, we will discuss the interesting aspect of terminology, since uNK cells are probably one of the human cells with the highest number of synonymous names, leading to significant discrepancies in their descriptions in scientific literature. From the first description of this cell type, they were referred to as endometrial granulocytes, granular endometrial stromal cells, or large granular lymphocytes until the end of the 1980s and the beginning of the 1990s of the last century, when the first publications appeared where the name “uterine NK cells” was used. The third area of present review is medical teaching of histology and clinical embryology. We can confirm that uNK cells are, in most textbooks, overlooked and almost forgotten cells despite their enormous importance. In the present narrative review, we summarize the lesser-known historical and terminological facts about uNK cells. We can state that within the textbooks of histology and embryology, this important cell population is still “overlooked and neglected” and is not given the same importance as in fields of clinical research and clinical practice. Full article
(This article belongs to the Special Issue Reproductive Immunology and Pregnancy 3.0)
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23 pages, 1567 KiB  
Review
Pathophysiological Insight into Fatty Acid-Binding Protein-4: Multifaced Roles in Reproduction, Pregnancy, and Offspring Health
by Yue Shi, Chi-Chiu Wang, Liqun Wu, Yunqing Zhang, Aimin Xu and Yao Wang
Int. J. Mol. Sci. 2023, 24(16), 12655; https://doi.org/10.3390/ijms241612655 - 10 Aug 2023
Cited by 4 | Viewed by 2403
Abstract
Fatty acid-binding protein-4 (FABP4), commonly known as adipocyte-fatty acid-binding protein (A-FABP), is a pleiotropic adipokine that broadly affects immunity and metabolism. It has been increasingly recognized that FABP4 dysfunction is associated with various metabolic syndromes, including obesity, diabetes, cardiovascular diseases, and metabolic inflammation. [...] Read more.
Fatty acid-binding protein-4 (FABP4), commonly known as adipocyte-fatty acid-binding protein (A-FABP), is a pleiotropic adipokine that broadly affects immunity and metabolism. It has been increasingly recognized that FABP4 dysfunction is associated with various metabolic syndromes, including obesity, diabetes, cardiovascular diseases, and metabolic inflammation. However, its explicit roles within the context of women’s reproduction and pregnancy remain to be investigated. In this review, we collate recent studies probing the influence of FABP4 on female reproduction, pregnancy, and even fetal health. Elevated circulating FABP4 levels have been found to correlate with impaired reproductive function in women, such as polycystic ovary syndrome and endometriosis. Throughout pregnancy, FABP4 affects maternal–fetal interface homeostasis by affecting both glycolipid metabolism and immune tolerance, leading to adverse pregnancy outcomes, including miscarriage, gestational obesity, gestational diabetes, and preeclampsia. Moreover, maternal FABP4 levels exhibit a substantial linkage with the metabolic health of offspring. Herein, we discuss the emerging significance and potential application of FABP4 in reproduction and pregnancy health and delve into its underlying mechanism at molecular levels. Full article
(This article belongs to the Special Issue Reproductive Immunology and Pregnancy 3.0)
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14 pages, 1672 KiB  
Review
HLA-G and Recurrent Pregnancy Loss
by Greta Barbaro, Annalisa Inversetti, Martina Cristodoro, Carlo Ticconi, Giovanni Scambia and Nicoletta Di Simone
Int. J. Mol. Sci. 2023, 24(3), 2557; https://doi.org/10.3390/ijms24032557 - 29 Jan 2023
Cited by 22 | Viewed by 4276
Abstract
Placentation is an immunological compromise where maternal immune system cells and trophoblastic cells interact to reach an equilibrium condition. Although the cross talk between the two systems is complex and not completely understood, Human Leukocyte Antigen G (HLA-G), expressed on trophoblastic cell surfaces, [...] Read more.
Placentation is an immunological compromise where maternal immune system cells and trophoblastic cells interact to reach an equilibrium condition. Although the cross talk between the two systems is complex and not completely understood, Human Leukocyte Antigen G (HLA-G), expressed on trophoblastic cell surfaces, seems to be one of the main molecules involved in the modulation of both local and systemic maternal immune response. The prevalence of recurrent pregnancy loss (RPL), probably underestimated, is 5% of all women who achieve pregnancy, and about 40–60% percent of RPL cases are unexplained. There is an immunological analogy between allograft rejection and miscarriage, and the purpose of this review is to describe how the HLA-G pathway alterations are involved in disrupting the immunologic balance and in increasing the risk of recurrent pregnancy loss. Full article
(This article belongs to the Special Issue Reproductive Immunology and Pregnancy 3.0)
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16 pages, 1005 KiB  
Review
Natural Killer Cell Receptors and Endometriosis: A Systematic Review
by José Lourenço Reis, Natacha Nurdine Rosa, Miguel Ângelo-Dias, Catarina Martins, Luís Miguel Borrego and Jorge Lima
Int. J. Mol. Sci. 2023, 24(1), 331; https://doi.org/10.3390/ijms24010331 - 25 Dec 2022
Cited by 9 | Viewed by 3200
Abstract
Endometriosis is a chronic inflammatory disorder, characterized by the presence of endometrial cells outside the uterine cavity. An increasing number of studies correlate the immune system with endometriosis, particularly NK receptors (NKR), which have been suggested to play an essential role in the [...] Read more.
Endometriosis is a chronic inflammatory disorder, characterized by the presence of endometrial cells outside the uterine cavity. An increasing number of studies correlate the immune system with endometriosis, particularly NK receptors (NKR), which have been suggested to play an essential role in the pathogenesis of the disease. This systematic review aims to enlighten the role of NKR in endometriosis. A literature search was performed independently by two reviewers, to identify studies assessing the role of NKR in endometriosis. In total, 18 studies were included. Endometriosis pathogenesis seems to be marked by the overexpression of NK inhibitor receptors (KIRS), namely, CD158a+, KIR2DL1, CD94/NKG2A, PD-1, NKB1, and EB6, and inhibiting ligands such as PD-L1, HLA-E, HLA-G, and HLA-I. Concurrently, there is a decrease in NK-activating receptors and natural cytotoxicity receptors (NCRs), such as NKp46, NKp30, and NKG2D. The immune shift from NK surveillance to NK suppression is also apparent in the greater relative number of ITIM domains compared with ITAM domains in NKRs. In conclusion, NK receptor activity seems to dictate the immunocompetency of women to clear endometriotic cells from the peritoneal cavity. Future research could explore NKRs as therapeutic targets, such as that which is now well established in cancer therapy through immunotherapy. Full article
(This article belongs to the Special Issue Reproductive Immunology and Pregnancy 3.0)
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