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Reproductive Immunology and Pregnancy 2.0
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Reproductive Immunology and Pregnancy 2.0

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 July 2022) | Viewed by 13898

Special Issue Editor

Prof. Dr. Dariusz Szukiewicz

E-Mail Website
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
Special Issues, Collections and Topics in MDPI journals

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.

Prof. Dr. Dariusz Szukiewicz
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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

Related Special Issues

Published Papers (5 papers)

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Research

16 pages, 4082 KiB  
Article
Uterine Deletion of Bmal1 Impairs Placental Vascularization and Induces Intrauterine Fetal Death in Mice
by Masanori Ono, Natsumi Toyoda, Kyosuke Kagami, Takashi Hosono, Takeo Matsumoto, Shin-ichi Horike, Rena Yamazaki, Mitsuhiro Nakamura, Yasunari Mizumoto, Tomoko Fujiwara, Hitoshi Ando, Hiroshi Fujiwara and Takiko Daikoku
Int. J. Mol. Sci. 2022, 23(14), 7637; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23147637 - 11 Jul 2022
Cited by 4 | Viewed by 2369
Abstract
Recently, it was demonstrated that the expression of BMAL1 was decreased in the endometrium of women suffering from recurrent spontaneous abortion. To investigate the pathological roles of uterine clock genes during pregnancy, we produced conditional deletion of uterine Bmal1 (cKO) mice and found [...] Read more.
Recently, it was demonstrated that the expression of BMAL1 was decreased in the endometrium of women suffering from recurrent spontaneous abortion. To investigate the pathological roles of uterine clock genes during pregnancy, we produced conditional deletion of uterine Bmal1 (cKO) mice and found that cKO mice could receive embryo implantation but not sustain pregnancy. Gene ontology analysis of microarray suggested that uterine NK (uNK) cell function was suppressed in cKO mice. Histological examination revealed the poor formation of maternal vascular spaces in the placenta. In contrast to WT mice, uNK cells in the spongiotrophoblast layer, where maternal uNK cells are directly in contact with fetal trophoblast, hardly expressed an immunosuppressive NK marker, CD161, in cKO mice. By progesterone supplementation, pregnancy could be sustained until the end of pregnancy in some cKO mice. Although this treatment did not improve the structural abnormalities of the placenta, it recruited CD161-positive NK cells into the spongiotrophoblast layer in cKO mice. These findings indicate that the uterine clock system may be critical for pregnancy maintenance after embryo implantation. Full article
(This article belongs to the Special Issue Reproductive Immunology and Pregnancy 2.0)
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18 pages, 2457 KiB  
Article
Isolation of Decidual Macrophages and Hofbauer Cells from Term Placenta—Comparison of the Expression of CD163 and CD80
by Manuel Lasch, Kritika Sudan, Corinna Paul, Christian Schulz, Thomas Kolben, Julia van Dorp, Sibel Eren, Susanne Beyer, Lorenzo Siniscalchi, Sven Mahner, Udo Jeschke and Sarah Meister
Int. J. Mol. Sci. 2022, 23(11), 6113; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23116113 - 30 May 2022
Cited by 5 | Viewed by 3028
Abstract
(1) Background: Placental immune cells are playing a very important role in a successful placentation and the prevention of pregnancy complications. Macrophages dominate in number and relevance in the maternal and the fetal part of the placenta. The evidence on the polarization state [...] Read more.
(1) Background: Placental immune cells are playing a very important role in a successful placentation and the prevention of pregnancy complications. Macrophages dominate in number and relevance in the maternal and the fetal part of the placenta. The evidence on the polarization state of fetal and maternal macrophages involved in both, healthy and pregnancy-associated diseases, is limited. There is no representative isolation method for the direct comparison of maternal and fetal macrophages so far. (2) Material and Methods: For the isolation of decidual macrophages and Hofbauer cells from term placenta, fresh tissue was mechanically dissected and digested with trypsin and collagenase A. Afterwards cell enrichment was increased by a Percoll gradient. CD68 is represented as pan-macrophage marker, the surface markers CD80 and CD163 were further investigated. (3) Results: The established method revealed a high cell yield and purity of the isolated macrophages and enabled the comparison between decidual macrophages and Hofbauer cells. No significant difference was observed in the percentage of single CD163+ cells in the distinct macrophage populations, by using FACS and immunofluorescence staining. A slight increase of CD80+ cells could be found in the decidual macrophages. Considering the percentage of CD80+CD163− and CD80−CD163+ cells we could not find differences. Interestingly we found an increased number of double positive cells (CD80+CD163+) in the decidual macrophage population in comparison to Hofbauer cells. (4) Conclusion: In this study we demonstrate that our established isolation method enables the investigation of decidual macrophages and Hofbauer cells in the placenta. It represents a promising method for direct cell comparison, enzyme independently, and unaffected by magnetic beads, to understand the functional subsets of placental macrophages and to identify therapeutic targets of pregnancy associated diseases. Full article
(This article belongs to the Special Issue Reproductive Immunology and Pregnancy 2.0)
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17 pages, 5993 KiB  
Article
miR-132-3p Modulates DUSP9-Dependent p38/JNK Signaling Pathways to Enhance Inflammation in the Amnion Leading to Labor
by Zhuxia Zhong, Zezhang Liu, Rong Zheng, Jin Chai and Siwen Jiang
Int. J. Mol. Sci. 2022, 23(3), 1864; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031864 - 07 Feb 2022
Cited by 2 | Viewed by 2179
Abstract
Labor is a process of inflammation and hormonal changes involving both fetal and maternal compartments. MicroRNA-132-3p (miR-132-3p) has been reported to be involved in the development of inflammation-related diseases. However, little is known about its potential role in labor onset. This study aimed [...] Read more.
Labor is a process of inflammation and hormonal changes involving both fetal and maternal compartments. MicroRNA-132-3p (miR-132-3p) has been reported to be involved in the development of inflammation-related diseases. However, little is known about its potential role in labor onset. This study aimed to explore the mechanism of miR-132-3p in amnion for labor initiation. In the mouse amnion membranes, the expression of miR-132-3p was found to increase gradually during late gestation. In human amniotic epithelial cell line (WISH), upregulation of miR-132-3p was found to increase proinflammatory cytokines and cyclooxygenase 2 (COX2) as well as prostaglandin E2 (PGE2), which was suppressed by miR-132-3p inhibitor. Dual-specificity phosphatase 9 (DUSP9) was identified as a novel target gene of miR-132-3p, which could be negatively regulated by miR-132-3p. DUSP9 was present in the mouse amnion epithelial cells, with a decrease in its abundance at 18.5 days post coitum (dpc) relative to 15.5 dpc. Silencing DUSP9 was found to facilitate the expression of proinflammatory cytokines and COX2 as well as PGE2 secretion in WISH cells, which could be attenuated by p38 inhibitor SB203580 or JNK inhibitor SP600125. Additionally, intraperitoneal injection of pregnant mice with miR-132-3p agomir not only caused preterm birth, but also promoted the abundance of COX2 as well as phosphorylated JNK and p38 levels, and decreased DUSP9 level in mouse amnion membranes. Collectively, miR-132-3p might participate in inflammation and PGE2 release via targeting DUSP9-dependent p38 and JNK signaling pathways to cause preterm birth. Full article
(This article belongs to the Special Issue Reproductive Immunology and Pregnancy 2.0)
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16 pages, 4505 KiB  
Article
CD91 Derived Treg Epitope Modulates Regulatory T Lymphocyte Response, Regulates Expression of Costimulatory Molecules on Antigen-Presenting Cells, and Rescues Pregnancy in Mouse Pregnancy Loss Model
by Anna Ewa Kedzierska, Daria Lorek, Anna Slawek, Tomasz Grabowski and Anna Chelmonska-Soyta
Int. J. Mol. Sci. 2021, 22(14), 7296; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147296 - 07 Jul 2021
Cited by 4 | Viewed by 2412
Abstract
The loss of immune tolerance to fetal antigens may result in reproductive failure. The downregulated number and activity of T regulatory lymphocytes, which are critical for the establishment of immune tolerance to fetal antigens, during pregnancy may lead to miscarriage. The adoptive transfer [...] Read more.
The loss of immune tolerance to fetal antigens may result in reproductive failure. The downregulated number and activity of T regulatory lymphocytes, which are critical for the establishment of immune tolerance to fetal antigens, during pregnancy may lead to miscarriage. The adoptive transfer of Tregs prevents fetal loss in abortion-prone mice. Recently, we demonstrated that the administration of tregitopes, which are short peptides found in human and mouse immunoglobulins (IgGs), decreased the incidence of abortions in female CBA/J mice mated with DBA/2J mice. Here, two non-IgG source peptides (SGS and LKD) that can potentially bind to the major histocompatibility complex II (MHC II) with high affinity and induce Treg expansion were designed in silico. The immune dysregulation-induced pregnancy failure mouse model was used to evaluate the effect of SGS and LKD on immune response and pregnancy outcome. The fetal death rate in the SGS-treated group was lower than that in the phosphate-buffered saline-treated group. SGS and LKD upregulated the splenic pool of Tregs and modulated the T-helper cell (Th1)/Th2-related cytokine response at the preimplantation stage. Additionally, SGS and LKD downregulated the expression of CD80 and MHC class II molecules in splenic CD11c+ antigen-presenting cells. Thus, SGS treatment can result in beneficial pregnancy outcomes. Additionally, SGS peptide-mediated immunomodulation can be a potential therapeutic strategy for immune dysregulation-induced pregnancy failure. Full article
(This article belongs to the Special Issue Reproductive Immunology and Pregnancy 2.0)
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17 pages, 4291 KiB  
Article
Integrated Insight into the Molecular Mechanisms of Spontaneous Abortion during Early Pregnancy in Pigs
by Xupeng Zang, Ting Gu, Wenjing Wang, Chen Zhou, Yue Ding, Shengchen Gu, Zhiqian Xu, Yanshe Xie, Zicong Li, Gengyuan Cai, Bin Hu, Linjun Hong and Zhenfang Wu
Int. J. Mol. Sci. 2021, 22(12), 6644; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126644 - 21 Jun 2021
Cited by 9 | Viewed by 2617
Abstract
Due to the high rate of spontaneous abortion (SAB) in porcine pregnancy, there is a major interest and concern on commercial pig farming worldwide. Whereas the perturbed immune response at the maternal–fetal interface is an important mechanism associated with the spontaneous embryo loss [...] Read more.
Due to the high rate of spontaneous abortion (SAB) in porcine pregnancy, there is a major interest and concern on commercial pig farming worldwide. Whereas the perturbed immune response at the maternal–fetal interface is an important mechanism associated with the spontaneous embryo loss in the early stages of implantation in porcine, data on the specific regulatory mechanism of the SAB at the end stage of the implantation remains scant. Therefore, we used high-throughput sequencing and bioinformatics tools to analyze the healthy and arresting endometrium on day 28 of pregnancy. We identified 639 differentially expressed lncRNAs (DELs) and 2357 differentially expressed genes (DEGs) at the end stage of implantation, and qRT-PCR was used to verify the sequencing data. Gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and immunohistochemistry analysis demonstrated weaker immune response activities in the arresting endometrium compared to the healthy one. Using the lasso regression analysis, we screened the DELs and constructed an immunological competitive endogenous RNA (ceRNA) network related to SAB, including 4 lncRNAs, 11 miRNAs, and 13 genes. In addition, Blast analysis showed the applicability of the constructed ceRNA network in different species, and subsequently determined HOXA-AS2 in pigs. Our study, for the first time, demonstrated that the SAB events at the end stages of implantation is associated with the regulation of immunobiological processes, and a specific molecular regulatory network was obtained. These novel findings may provide new insight into the possibility of increasing the litter size of sows, making pig breeding better and thus improving the efficiency of animal husbandry production. Full article
(This article belongs to the Special Issue Reproductive Immunology and Pregnancy 2.0)
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