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Reproductive Immunology: Cellular and Molecular Biology 2.0
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Reproductive Immunology: Cellular and Molecular Biology 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 (30 April 2022) | Viewed by 27757

Special Issue Editors

Prof. Dr. Udo Jeschke

E-Mail Website
Guest Editor
Interdisciplinary Center of Experimental Tumor Research, University Hospital Augsburg, Stenglinstr. 2, 86156 Augsburg, Germany
Interests: ovarian cancer, breast cancer, cervical cancer, endometrial cancer, placenta
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Antonis Makrigiannakis

E-Mail Website
Guest Editor
Department of Obstetrics and Gynecology, Medical School, University of Crete, 71003 Heraklion, Greece
Interests: implantation; receptivity; endometrium; RIF; early pregnancy; trophoblast
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue on “Reproductive Immunology: Cellular and Molecular Biology”.

Reproductive immunology in the 21st century still deals with a problem that has been known for decades—the fetus as semi-allograft and its response to the maternal immune system. Therefore, there is a strong need to solve problems such as spontaneous and recurrent miscarriages and, in addition, repeated implantation failure.
Furthermore, socioeconomical changes in an aging society are an additional challenge especially for the reproductive medicine specialist. Although highly developed in vitro fertilization techniques are available, many couples still face the problem of childlessness.
A quite new player in the field is the microbiome of the reproductive tract. For decades, it was believed that the uterus is sterile but an up to date analysis revealed that we not only have a vaginal microbiome but also a cervical, uterine, male, and even a placental microbiome.
Therefore, we would like to invite our colleagues to submit articles that deal with cellular and molecular mechanisms in the field of reproductive immunology to this Special Issue.

Prof. Dr. Udo Jeschke
Prof. Dr. Antonis Makrigiannakis
Guest Editors

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

  • Spontaneous and recurrent miscarriage
  • Repeated implantation failure
  • Maternal immune cells
  • Microbiome
  • Assisted reproduction

Related Special Issues

Published Papers (6 papers)

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Research

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23 pages, 1277 KiB  
Article
At Embryo Implantation Site IL-35 Secreted by Trophoblast, Polarizing T Cells towards IL-35+ IL-10+ IL-4+ Th2-Type Cells, Could Favour Fetal Allograft Tolerance and Pregnancy Success
by Letizia Lombardelli, Federica Logiodice, Ornela Kullolli, Herman Haller, Chiara Agostinis, Roberta Bulla, Daniel Rukavina and Marie-Pierre Piccinni
Int. J. Mol. Sci. 2022, 23(9), 4926; https://doi.org/10.3390/ijms23094926 - 28 Apr 2022
Cited by 1 | Viewed by 4079
Abstract
We investigated the role of rhIL-35, at low concentrations compatible with those produced by human trophoblast cells (less than 1 ng/mL), on human T helper (Th) cell functions and the presence of decidual IL-35-producing Th cells in human pregnancy. We found that human [...] Read more.
We investigated the role of rhIL-35, at low concentrations compatible with those produced by human trophoblast cells (less than 1 ng/mL), on human T helper (Th) cell functions and the presence of decidual IL-35-producing Th cells in human pregnancy. We found that human trophoblast cells produced IL-35 but not IL-4 or IL-10. RhIL-35, at concentrations produced by human trophoblasts, polarized T cells towards IL-35+, IL-10+, IL-4+ Th2-type cells and to Foxp3+ EBI3+ p35+ T reg cells producing IL-35 but not IL-10 and IL-4. Moreover, rhIL-35 at low concentrations did not suppress the proliferation of Th cells but stimulated IL-4 and IL-10 production by established Th clones. In particular, Th1-type clones acquired the capacity to produce IL-4. In addition, purified human trophoblast cell supernatants containing IL-35 upregulated IL-4 and IL-10 production by Th clones. Finally, IL-35+, IL-10+, IL-4+ Th2-type cells, which were found to be induced by low concentrations of IL-35 compatible with those produced by human trophoblasts, are exclusively present in the decidua of a successful pregnancy and at the embryo implantation site, suggesting their stringent dependence on trophoblast cells. Thus, the proximity of Th cells to IL-35-producing trophoblasts could be the determining factor for the differentiation of IL-35+, IL-10+, IL-4+ Th2-type cells that are crucial for human pregnancy success. Full article
(This article belongs to the Special Issue Reproductive Immunology: Cellular and Molecular Biology 2.0)
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18 pages, 30504 KiB  
Article
Prostaglandin E2 Receptor 4 (EP4) Affects Trophoblast Functions via Activating the cAMP-PKA-pCREB Signaling Pathway at the Maternal-Fetal Interface in Unexplained Recurrent Miscarriage
by Lin Peng, Anca Chelariu-Raicu, Yao Ye, Zhi Ma, Huixia Yang, Hellen Ishikawa-Ankerhold, Martina Rahmeh, Sven Mahner, Udo Jeschke and Viktoria von Schönfeldt
Int. J. Mol. Sci. 2021, 22(17), 9134; https://doi.org/10.3390/ijms22179134 - 24 Aug 2021
Cited by 1 | Viewed by 2612
Abstract
Implantation consists of a complex process based on coordinated crosstalk between the endometrium and trophoblast. Furthermore, it is known that the microenvironment of this fetal–maternal interface plays an important role in the development of extravillous trophoblast cells. This is mainly due to the [...] Read more.
Implantation consists of a complex process based on coordinated crosstalk between the endometrium and trophoblast. Furthermore, it is known that the microenvironment of this fetal–maternal interface plays an important role in the development of extravillous trophoblast cells. This is mainly due to the fact that tissues mediate embryonic signaling biologicals, among other molecules, prostaglandins. Prostaglandins influence tissue through several cell processes including differentiation, proliferation, and promotion of maternal immune tolerance. The aim of this study is to investigate the potential pathological mechanism of the prostaglandin E2 receptor 4 (EP4) in modulating extravillous trophoblast cells (EVTs) in unexplained recurrent marriage (uRM). Our results indicated that the expression of EP4 in EVTs was decreased in women experiencing uRM. Furthermore, silencing of EP4 showed an inhibition of the proliferation and induced apoptosis in vitro. In addition, our results demonstrated reductions in β- human chorionic gonadotropin (hCG), progesterone, and interleukin (IL)-6, which is likely a result from the activation of the cyclic adenosine monophosphate (cAMP)- cAMP-dependent protein kinase A (PKA)-phosphorylating CREB (pCREB) pathway. Our data might provide insight into the mechanisms of EP4 linked to trophoblast function. These findings help build a more comprehensive understanding of the effects of EP4 on the trophoblast at the fetal–maternal interface in the first trimester of pregnancy. Full article
(This article belongs to the Special Issue Reproductive Immunology: Cellular and Molecular Biology 2.0)
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20 pages, 5909 KiB  
Article
Comparison of Histone H3K4me3 between IVF and ICSI Technologies and between Boy and Girl Offspring
by Huixia Yang, Zhi Ma, Lin Peng, Christina Kuhn, Martina Rahmeh, Sven Mahner, Udo Jeschke and Viktoria von Schönfeldt
Int. J. Mol. Sci. 2021, 22(16), 8574; https://doi.org/10.3390/ijms22168574 - 09 Aug 2021
Cited by 10 | Viewed by 3303
Abstract
Epigenetics play a vital role in early embryo development. Offspring conceived via assisted reproductive technologies (ARTs) have a three times higher risk of epigenetic diseases than naturally conceived children. However, investigations into ART-associated placental histone modifications or sex-stratified analyses of ART-associated histone modifications [...] Read more.
Epigenetics play a vital role in early embryo development. Offspring conceived via assisted reproductive technologies (ARTs) have a three times higher risk of epigenetic diseases than naturally conceived children. However, investigations into ART-associated placental histone modifications or sex-stratified analyses of ART-associated histone modifications remain limited. In the current study, we carried out immunohistochemistry, chip-sequence analysis, and a series of in vitro experiments. Our results demonstrated that placentas from intra-cytoplasmic sperm injection (ICSI), but not in vitro fertilization (IVF), showed global tri-methylated-histone-H3-lysine-4 (H3K4me3) alteration compared to those from natural conception. However, for acetylated-histone-H3-lysine-9 (H3K9ac) and acetylated-histone-H3-lysine-27 (H3K27ac), no significant differences between groups could be found. Further, sex -stratified analysis found that, compared with the same-gender newborn cord blood mononuclear cell (CBMC) from natural conceptions, CBMC from ICSI-boys presented more genes with differentially enriched H3K4me3 (n = 198) than those from ICSI-girls (n = 79), IVF-girls (n = 5), and IVF-boys (n = 2). We also found that varying oxygen conditions, RNA polymerase II subunit A (Polr2A), and lysine demethylase 5A (KDM5A) regulated H3K4me3. These findings revealed a difference between IVF and ICSI and a difference between boys and girls in H3K4me3 modification, providing greater insight into ART-associated epigenetic alteration. Full article
(This article belongs to the Special Issue Reproductive Immunology: Cellular and Molecular Biology 2.0)
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Review

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13 pages, 621 KiB  
Review
Effect of Endogenic and Exogenic Oxidative Stress Triggers on Adverse Pregnancy Outcomes: Preeclampsia, Fetal Growth Restriction, Gestational Diabetes Mellitus and Preterm Birth
by Eun Hui Joo, Young Ran Kim, Nari Kim, Jae Eun Jung, Seon Ha Han and Hee Young Cho
Int. J. Mol. Sci. 2021, 22(18), 10122; https://doi.org/10.3390/ijms221810122 - 19 Sep 2021
Cited by 55 | Viewed by 5360
Abstract
Oxidative stress is caused by an imbalance between the production of reactive oxygen species (ROS) in cells and tissues and the ability of a biological system to detoxify them. During a normal pregnancy, oxidative stress increases the normal systemic inflammatory response and is [...] Read more.
Oxidative stress is caused by an imbalance between the production of reactive oxygen species (ROS) in cells and tissues and the ability of a biological system to detoxify them. During a normal pregnancy, oxidative stress increases the normal systemic inflammatory response and is usually well-controlled by the balanced body mechanism of the detoxification of anti-oxidative products. However, pregnancy is also a condition in which this adaptation and balance can be easily disrupted. Excessive ROS is detrimental and associated with many pregnancy complications, such as preeclampsia (PE), fetal growth restriction (FGR), gestational diabetes mellitus (GDM), and preterm birth (PTB), by damaging placentation. The placenta is a tissue rich in mitochondria that produces the majority of ROS, so it is important to maintain normal placental function and properly develop its vascular network to ensure a safe and healthy pregnancy. Antioxidants may ameliorate these diseases, and related research is progressing. This review aimed to determine the association between oxidative stress and adverse pregnancy outcomes, especially PE, FGR, GDM, and PTB, and explore how to overcome this oxidative stress in these unfavorable conditions. Full article
(This article belongs to the Special Issue Reproductive Immunology: Cellular and Molecular Biology 2.0)
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13 pages, 1891 KiB  
Review
Role of Peroxisome Proliferator-Activated Receptors (PPARs) in Trophoblast Functions
by Lin Peng, Huixia Yang, Yao Ye, Zhi Ma, Christina Kuhn, Martina Rahmeh, Sven Mahner, Antonis Makrigiannakis, Udo Jeschke and Viktoria von Schönfeldt
Int. J. Mol. Sci. 2021, 22(1), 433; https://doi.org/10.3390/ijms22010433 - 04 Jan 2021
Cited by 25 | Viewed by 3943
Abstract
Peroxisome proliferator-activated receptors (PPARα, PPARβ/δ, and PPARγ) belong to the transcription factor family, and they are highly expressed in all types of trophoblast during pregnancy. The present review discusses currently published papers that are related to the regulation of [...] Read more.
Peroxisome proliferator-activated receptors (PPARα, PPARβ/δ, and PPARγ) belong to the transcription factor family, and they are highly expressed in all types of trophoblast during pregnancy. The present review discusses currently published papers that are related to the regulation of PPARs via lipid metabolism, glucose metabolism, and amino acid metabolism to affect trophoblast physiological conditions, including differentiation, maturation, secretion, fusion, proliferation, migration, and invasion. Recent pieces of evidence have proven that the dysfunctions of PPARs in trophoblast lead to several related pregnancy diseases such as recurrent miscarriage, preeclampsia, intrauterine growth restriction, and gestational diabetes mellitus. Moreover, the underlying mechanisms of PPARs in the control of these processes have been discussed as well. Finally, this review’s purposes are to provide more knowledge about the role of PPARs in normal and disturbed pregnancy with trophoblast, so as to find PPAR ligands as a potential therapeutic target in the treatment and prevention of adverse pregnancy outcomes. Full article
(This article belongs to the Special Issue Reproductive Immunology: Cellular and Molecular Biology 2.0)
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19 pages, 1779 KiB  
Review
Early Life Oxidative Stress and Long-Lasting Cardiovascular Effects on Offspring Conceived by Assisted Reproductive Technologies: A Review
by Huixia Yang, Christina Kuhn, Thomas Kolben, Zhi Ma, Peng Lin, Sven Mahner, Udo Jeschke and Viktoria von Schönfeldt
Int. J. Mol. Sci. 2020, 21(15), 5175; https://doi.org/10.3390/ijms21155175 - 22 Jul 2020
Cited by 20 | Viewed by 7255
Abstract
Assisted reproductive technology (ART) has rapidly developed and is now widely practised worldwide. Both the characteristics of ART (handling gametes/embryos in vitro) and the infertility backgrounds of ART parents (such as infertility diseases and unfavourable lifestyles or diets) could cause increased oxidative stress [...] Read more.
Assisted reproductive technology (ART) has rapidly developed and is now widely practised worldwide. Both the characteristics of ART (handling gametes/embryos in vitro) and the infertility backgrounds of ART parents (such as infertility diseases and unfavourable lifestyles or diets) could cause increased oxidative stress (OS) that may exert adverse influences on gametogenesis, fertilisation, and foetation, even causing a long-lasting influence on the offspring. For these reasons, the safety of ART needs to be closely examined. In this review, from an ART safety standpoint, the origins of OS are reviewed, and the long-lasting cardiovascular effects and potential mechanisms of OS on the offspring are discussed. Full article
(This article belongs to the Special Issue Reproductive Immunology: Cellular and Molecular Biology 2.0)
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