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Reproductive Immunology: New Insights into Physiology and Pathophysiology of Pregnancy
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Reproductive Immunology: New Insights into Physiology and Pathophysiology of Pregnancy

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 (31 October 2023) | Viewed by 7354

Special Issue Editors

Dr. Marie-Pierre Piccinni

E-Mail Website
Guest Editor
Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
Interests: immunology; reproductive immunology; pregnancy; autoimmune; inflammatory disorders
Prof. Dr. Julia Szekeres-Bartho

E-Mail Website
Guest Editor
National Laboratory for Human Reproduction, University of Pécs, 7624 Pécs, Hungary
Interests: blocking factor; habitual abortion; progesterone; trophoblasts; decidua; natural killer cells
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Sandra Maria Blois

E-Mail Website
Guest Editor
Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Interests: pregancy; natural killer cells

Special Issue Information

Dear Colleagues, 

Though several underlying pathologies have been identified, 15% of female infertilities remain unexplained. Treatment options are still scarce. However, some of the problems can be solved through assisted reproductive technologies. Deficient endometrium receptivity, inadequate development, or poor implantation capacity of the embryo represent the most common causes of female infertility.

Immune cells play crucial roles in maintaining fertility and securing a successful pregnancy outcome, by influencing follicular/embryo development and endometrial receptivity, including vascular maternal adaptation.

The comprehension of the uterine and ovarian immune cellular and molecular mechanisms is essential for developing more efficient ways not only to treat reproductive issues but also to define the indications for immune checkpoints as a novel therapeutic option in reproductive clinical practice.

This Special Issue aims to highlight the emerging areas of research within the reproductive immunology field and contribute to a better understanding of the immune cellular and molecular mechanisms, together with the observed clinical outcomes, which could be essential for defining the indications for immune therapeutic options in managing infertility and pregnancy pathologies.

Dr. Marie-Pierre Piccinni
Prof. Dr. Julia Szekeres-Bartho
Prof. Dr. Sandra Maria Blois
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.

Published Papers (4 papers)

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Research

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16 pages, 2235 KiB  
Article
Cyclophilin A as a Pro-Inflammatory Factor Exhibits Embryotoxic and Teratogenic Effects during Fetal Organogenesis
by Anastasiia Kalinina, Maria Semenova, Alexandra Bruter, Ekaterina Varlamova, Marina Kubekina, Natalia Pavlenko, Yulia Silaeva, Alexey Deikin, Elena Antoshina, Tatyana Gorkova, Lubov Trukhanova, Alla Salmina, Svetlana Novikova, Dmitry Voronkov, Dmitry Kazansky and Ludmila Khromykh
Int. J. Mol. Sci. 2023, 24(14), 11279; https://doi.org/10.3390/ijms241411279 - 10 Jul 2023
Viewed by 1270
Abstract
The precise balance of Th1, Th2, and Th17 cytokines is a key factor in successful pregnancy and normal embryonic development. However, to date, not all humoral factors that regulate and influence physiological pregnancy have been completely studied. Our data here pointed out cyclophilin [...] Read more.
The precise balance of Th1, Th2, and Th17 cytokines is a key factor in successful pregnancy and normal embryonic development. However, to date, not all humoral factors that regulate and influence physiological pregnancy have been completely studied. Our data here pointed out cyclophilin A (CypA) as the adverse pro-inflammatory factor negatively affecting fetal development and associated with pregnancy complications. In different mouse models in vivo, we demonstrated dramatic embryotoxicity and teratogenicity of increased CypA levels during pregnancy. Using generated transgenic models, we showed that CypA overexpression in fetal tissues induced the death of all transgenic fetuses and complete miscarriage. Administration of recombinant human CypA in a high dose to pregnant females during fetal organogenesis (6.5–11.5 dpc) exhibited teratogenic effects, causing severe defects in the brain and bone development that could lead to malformations and postnatal behavioral and cognitive disorders in the offspring. Embryotoxic and teratogenic effects could be mediated by CypA-induced up-regulation of M1 macrophage polarization via activation of the STAT1/3 signaling pathways. Here, we propose secreted CypA as a novel marker of complicated pregnancy and a therapeutic target for the correction of pregnancy complications. Full article
(This article belongs to the Special Issue Reproductive Immunology: New Insights into Physiology and Pathophysiology of Pregnancy)
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18 pages, 2046 KiB  
Article
Pyroptosis: A Promising Mechanism Linking SARS-CoV-2 Infection to Adverse Pregnancy Outcomes
by Paola Monti, Giulia Solazzo, Veronica Accurti, Bianca Gambitta, Simona Iodice, Simona Boito, Laura Cantone, Alessandro Manenti, Laura Dioni, Emanuele Montomoli, Nicola Persico and Valentina Bollati
Int. J. Mol. Sci. 2023, 24(11), 9278; https://doi.org/10.3390/ijms24119278 - 25 May 2023
Cited by 1 | Viewed by 1660
Abstract
Pregnancy is characterized by a delicate immune balance; therefore, infectious diseases might increase the risk of adverse pregnancy outcomes (APOs). Here, we hypothesize that pyroptosis, a unique cell death pathway mediated by the NLRP3 inflammasome, could link SARS-CoV-2 infection, inflammation, and APOs. Two [...] Read more.
Pregnancy is characterized by a delicate immune balance; therefore, infectious diseases might increase the risk of adverse pregnancy outcomes (APOs). Here, we hypothesize that pyroptosis, a unique cell death pathway mediated by the NLRP3 inflammasome, could link SARS-CoV-2 infection, inflammation, and APOs. Two blood samples were collected from 231 pregnant women at 11–13 weeks of gestation and in the perinatal period. At each time point, SARS-CoV-2 antibodies and neutralizing antibody titers were measured by ELISA and microneutralization (MN) assays, respectively. Plasmatic NLRP3 was determined by ELISA. Fourteen miRNAs selected for their role in inflammation and/or pregnancy were quantified by qPCR and further investigated by miRNA-gene target analysis. NLRP3 levels were positively associated with nine circulating miRNAs, of which miR-195-5p was increased only in MN+ women (p-value = 0.017). Pre-eclampsia was associated with a decrease in miR-106a-5p (p-value = 0.050). miR-106a-5p (p-value = 0.026) and miR-210-3p (p-value = 0.035) were increased in women with gestational diabetes. Women giving birth to small for gestational age babies had lower miR-106a-5p and miR-21-5p (p-values = 0.001 and 0.036, respectively), and higher miR-155-5p levels (p-value = 0.008). We also observed that neutralizing antibodies and NLRP3 concentrations could affect the association between APOs and miRNAs. Our findings suggest for the first time a possible link between COVID-19, NLRP3-mediated pyroptosis, inflammation, and APOs. Circulating miRNAs might be suitable candidates to gain a comprehensive view of this complex interplay. Full article
(This article belongs to the Special Issue Reproductive Immunology: New Insights into Physiology and Pathophysiology of Pregnancy)
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Review

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27 pages, 8381 KiB  
Review
Long-Term Effects of ART on the Health of the Offspring
by Hamid Ahmadi, Leili Aghebati-Maleki, Shima Rashidiani, Timea Csabai, Obodo Basil Nnaemeka and Julia Szekeres-Bartho
Int. J. Mol. Sci. 2023, 24(17), 13564; https://doi.org/10.3390/ijms241713564 - 1 Sep 2023
Cited by 2 | Viewed by 2406
Abstract
Assisted reproductive technologies (ART) significantly increase the chance of successful pregnancy and live birth in infertile couples. The different procedures for ART, including in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), intrauterine insemination (IUI), and gamete intrafallopian tube transfer (GIFT), are widely used [...] Read more.
Assisted reproductive technologies (ART) significantly increase the chance of successful pregnancy and live birth in infertile couples. The different procedures for ART, including in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), intrauterine insemination (IUI), and gamete intrafallopian tube transfer (GIFT), are widely used to overcome infertility-related problems. In spite of its inarguable usefulness, concerns about the health consequences of ART-conceived babies have been raised. There are reports about the association of ART with birth defects and health complications, e.g., malignancies, high blood pressure, generalized vascular functional disorders, asthma and metabolic disorders in later life. It has been suggested that hormonal treatment of the mother, and the artificial environment during the manipulation of gametes and embryos may cause genomic and epigenetic alterations and subsequent complications in the health status of ART-conceived babies. In the current study, we aimed to review the possible long-term consequences of different ART procedures on the subsequent health status of ART-conceived offspring, considering the confounding factors that might account for/contribute to the long-term consequences. Full article
(This article belongs to the Special Issue Reproductive Immunology: New Insights into Physiology and Pathophysiology of Pregnancy)
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16 pages, 331 KiB  
Review
The Next Frontier in ART: Harnessing the Uterine Immune Profile for Improved Performance
by Nathalie Lédée, Marie Petitbarat, Laura Prat-Ellenberg, Géraldine Dray, Virginie Vaucoret, Alaa Kazhalawi, André Rodriguez-Pozo, Nada Habeichi, Lea Ruoso, Nino Guy Cassuto and Mona Rahmati
Int. J. Mol. Sci. 2023, 24(14), 11322; https://doi.org/10.3390/ijms241411322 - 11 Jul 2023
Viewed by 1438
Abstract
Assisted reproduction techniques have improved considerably in recent decades, but despite these advances, success rates remain relatively low. Endometrial immune profiling involves the analysis of cytokine biomarkers in the endometrium during the mid-luteal phase. This profiling aims to provide insights into the immune [...] Read more.
Assisted reproduction techniques have improved considerably in recent decades, but despite these advances, success rates remain relatively low. Endometrial immune profiling involves the analysis of cytokine biomarkers in the endometrium during the mid-luteal phase. This profiling aims to provide insights into the immune environment of the uterus. The aim is to identify immune disturbances and thus guide the development of personalized therapeutic approaches. The first part of the review looks back at the emergence of innovative concepts, highlighting the specificity of the human uterine environment at the time of implantation. Based on this new knowledge, biomarkers have been selected for endometrial immune profiling. The second part details the results of clinical studies conducted over the last ten years. These clinical results suggest that this approach can increase the rate of live births in patients suffering from repeated implantation failures or repeated pregnancy loss. Uterine immune profiling represents a clinical innovation that can significantly improve the performance of medically assisted reproduction treatments through personalized strategies tailored to the local immune profile. Innovation in personalized medicine for assisted reproduction is crucial to improving the success rates of fertility treatments, while reducing the risks and costs associated with ineffective or unnecessary interventions. Full article
(This article belongs to the Special Issue Reproductive Immunology: New Insights into Physiology and Pathophysiology of Pregnancy)
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