Article
Immunology
Yun Liu, Peigen Chen, Hui Fei, Mengxiong Li, Xian Li, Tian Li
Summary: In this study, analysis of endometrial tissue data from patients with recurrent miscarriage revealed a key module positively related to the numbers of miscarriages, with natural killer cells mediated cytotoxicity related genes playing a role. Specifically, CASP3 was identified as a key gene that down-regulates PARP1, with regulation by SP1. It was proposed that natural killer cells contribute to recurrent miscarriage through the SP1-CASP3-PARP1 pathway.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Review
Obstetrics & Gynecology
Ee Von Woon, Orene Greer, Nishel Shah, Dimitrios Nikolaou, Mark Johnson, Victoria Male
Summary: Studies have found significantly increased levels of uterine natural killer cells in women with recurrent miscarriage and recurrent implantation failure, which may contribute to implantation or placental development failure. While results on cytokine secretion varied among studies, most research indicated lower expression of inhibitory receptors and higher expression of angiogenic factors in women with recurrent miscarriage.
HUMAN REPRODUCTION UPDATE
(2022)
Review
Immunology
Rodolfo R. Favaro, Katherine Phillips, Romane Delaunay-Danguy, Kaja Ujcic, Udo R. Markert
Summary: Members of the innate immune system, specifically innate lymphoid cells (ILCs), play important roles in the uterine environment, supporting pregnancy and placental development. These cells demonstrate immune memory, allowing them to remember previously encountered antigens and mount enhanced responses. By studying ILCs, we can gain insights into the immunological mechanisms underlying female fertility/infertility, placental development, and distinct outcomes in second pregnancies.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Oisin Huhn, Xiaohui Zhao, Laura Esposito, Ashley Moffett, Francesco Colucci, Andrew M. Sharkey
Summary: Innate lymphoid cells (ILCs) are the most abundant immune cells in the uterine mucosa before and during pregnancy, with tissue-resident natural killer (NK) cells and ILCs being the main subsets. Recent advances in single-cell RNA sequencing and high dimensional flow and mass cytometry have significantly enhanced our understanding of the heterogeneity within the uILC compartment. These advancements may help answer key clinical questions regarding infertility, miscarriage, and pregnancy disorders related to uILC subsets.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Marcelo Borges Cavalcante, Pedro Henrique Alcantara da Silva, Thiago Ribeiro Carvalho, Olga Goiana Martins Sampaio, Fernanda Eunice Araujo Camara, Candice Torres de Melo Bezerra Cavalcante, Ricardo Barini, Joanne Kwak-Kim
Summary: This systematic review and meta-analysis aimed to investigate the difference in peripheral blood natural killer cell cytotoxicities (pNKCs) between nonpregnant and pregnant women with recurrent miscarriages (RM) and controls, and to determine if immunotherapy can reduce pNKCs. Results showed that both nonpregnant and pregnant women with RM had higher pNKCs compared to controls, and pNKCs were significantly reduced after immunotherapy. However, there were heterogeneities among the included studies regarding patient inclusion criteria, techniques used to measure pNKC, and types of immunotherapies.
JOURNAL OF REPRODUCTIVE IMMUNOLOGY
(2023)
Article
Cell Biology
Ying Li, O. D. A. Harunori, Shihu Fu, Fuyuan Xing, Huawan Wu, Juan Wang, Aihua Chen, Xinhua Ren, Dawei Peng, Xia Ling, Ming Shi, Hongjin Wu
Summary: Immune normalization, a new paradigm in immunotherapy, can be used in cancer patients and sub-healthy individuals for cancer prevention. In vitro cultured mixed natural killer (NKM) cells show high cytotoxicity, positively correlated with NK cell proportion. Sub-healthy individuals and cancer patients treated with NKM-cell therapy demonstrated reduced T cell percentage and good tolerance.
Article
Medicine, General & Internal
Anne-Sophie Braun, Kilian Vomstein, Elisabeth Reiser, Susanne Tollinger, Christiana Kyvelidou, Katharina Feil, Bettina Toth
Summary: RPL and RIF are challenges in reproductive medicine. The immune system plays a pivotal role in endometrial receptivity, successful implantation, and pregnancy complications. Understanding immune dysregulation especially in NK and T cell subtypes may lead to better diagnostic concepts and treatments. Tailored immunotherapy based on endometrial immunophenotyping might be an option for RPL and RIF patients, but further research is needed.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Chow-Seng Kong, Alexandra Almansa Ordonez, Sarah Turner, Tina Tremaine, Joanne Muter, Emma S. Lucas, Emma Salisbury, Rita Vassena, Gustavo Tiscornia, Ali A. Fouladi-Nashta, Geraldine Hartshorne, Jan J. Brosens, Paul J. Brighton
Summary: The study found that uterine natural killer cells play a crucial role in embryo biosensing and implantation process, highlighting their importance in selectively eliminating senescent decidual cells.
Review
Cell Biology
Jan J. Brosens, Phillip R. Bennett, Vikki M. Abrahams, Rosanna Ramhorst, Arri Coomarasamy, Siobhan Quenby, Emma S. Lucas, Rajiv C. McCoy
Summary: Compared to other mammals, human pregnancy is unique in its involvement of chromosomally diverse embryos and the cyclical breakdown and regeneration of the uterine mucosa. Understanding the mechanisms behind miscarriage can provide insights into the maternal selection of embryos during early gestation.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Reproductive Biology
Donghai Zhang, Yongsheng Yu, Chuanfeng Ding, Ruonan Zhang, Tao Duan, Qian Zhou
Summary: Decreased B7-H3 inhibits trophoblast migration and invasion in unexplained recurrent miscarriage, as well as regulates IL-8 and IP-10 secretion from decidual natural killer cells. The study reveals a possible mechanism for the role of B7-H3 in unexplained recurrent miscarriage and suggests it as a potential therapeutic target.
BIOLOGY OF REPRODUCTION
(2023)
Article
Obstetrics & Gynecology
Isabel Cuadrado-Torroglosa, Alberto Pacheco, Ana Barrio, Nicolas Garrido, Pilar Aparicio, Nuria Pellicer, Juan Antonio Garcia-Velasco, Diana Alecsandru
Summary: This study aims to investigate the distribution and gene expression of endometrial immune cell populations, especially natural killer (NK) subsets, in assisted reproductive technology patients and healthy donors. The results showed a higher percentage of CD56dimCD16 thorn NK cells in patients compared to healthy donors. However, there was no statistically significant difference in endometrial gene expression or immune cell populations when categorizing patients by KIR genotype. Furthermore, there were no differences in binding between KIR and HLA-C molecules among these patient groups.
FERTILITY AND STERILITY
(2023)
Article
Biochemistry & Molecular Biology
Lucas Henrique Rodrigues da Silva, Luana Correia Croda Catharino, Viviane Jennifer da Silva, Gabriela Coeli Menezes Evangelista, Jose Alexandre Marzagao Barbuto
Summary: Natural killer (NK) cells are innate lymphocytes that play a vital role in immune surveillance against tumors. Various NK-based therapies, including transfer of expanded and activated cells, genetic engineering, cytokine therapy, and tumor-specific antibody-guided cells, are being used in cancer treatment. This article also discusses the potential approaches to control glioblastoma.
Article
Obstetrics & Gynecology
Pirkko Peuranpaea, Tiina Holster, Schahzad Saqib, Ilkka Kalliala, Aila Tiitinen, Anne Salonen, Hanna Hautamaki
Summary: This study found that dysbiosis of the endometrial and vaginal microbiota is associated with recurrent pregnancy loss and may represent a novel risk factor for pregnancy loss. Specifically, there was a decrease in relative abundance of Lactobacillus crispatus in endometrial samples and an increase in Gardnerella vaginalis abundance in the RPL group.
REPRODUCTIVE BIOMEDICINE ONLINE
(2022)
Article
Microbiology
Yongwei Qin, Qinglan Wang, Jiahai Shi
Summary: The down-regulated expression of immune-activating receptors and enhanced expression of immune-inhibitory receptors play a role in chronic infectious diseases and cancer. However, the impact of Mycobacterium tuberculosis infection on the expression of immune checkpoint molecules on natural killer (NK) cells and their functions has been poorly studied. Understanding the function of NK cells during Mtb infection is crucial for a comprehensive understanding of the immune mechanism and evaluation of immunotherapies for treating tuberculosis.
MICROBIOLOGICAL RESEARCH
(2023)
Article
Engineering, Mechanical
Francisco J. Solis, Luz M. Gonzalez
Summary: In this paper, a nonlinear advection-diffusion model is proposed to study the interaction between immune system cells and HPV-infected cells. The model considers both the innate and adaptive immune response. A numerical explicit scheme is presented to approximate the proposed model. Numerical simulations show the temporal evolution of the model cells and identify conditions for eliminating the infection.
NONLINEAR DYNAMICS
(2023)
Review
Biochemistry & Molecular Biology
Diana M. Morales-Prieto, Paulina Fuentes-Zacarias, Jose M. Murrieta-Coxca, Ruby N. Gutierrez-Samudio, Rodolfo R. Favaro, Justine S. Fitzgerald, Udo R. Markert
Summary: Tobacco smoking is a major public health issue that has negative effects on pregnancy. This review examines the impact of smoking on immune regulation, placental function, and vascular development. The study aims to understand how maternal smoking affects placental function in both normal and pathological pregnancies. Smoking cessation is recommended for future mothers as the components of tobacco smoke can have detrimental effects on placental function.
MOLECULAR ASPECTS OF MEDICINE
(2022)
Article
Developmental Biology
Jose Martin Murrieta-Coxca, Leonie Aengenheister, Astrid Schmidt, Udo R. Markert, Tina Buerki-Thurnherr, Diana M. Morales-Prieto
Summary: The physical connection between mother and offspring during pregnancy allows for bi-directional exchange of cells, which can persist long-term in the recipient individual and play a role in immune adaptation and tolerogenic responses. However, the mechanisms of cell transfer across the placenta barrier are still poorly understood.
Article
Oncology
Elisabeth Reiser, Anna Lena Zippl, Kilian Vomstein, Elena Strassgschwandter, Susanne Hofer-Tollinger, Germar Michael Pinggera, Bettina Toth
Summary: This study investigated the association between sperm quality and sexual function in male cancer survivors, and found that more than one-third of patients had azoospermia, with ED primarily present in this subgroup. It is recommended to implement annual sperm testing and screen for sexual dysfunction in men after gonadotoxic treatment.
SUPPORTIVE CARE IN CANCER
(2022)
Correction
Health Care Sciences & Services
Maren Schick, Ariane Germeyer, Bettina Boettcher, Stephanie Hecht, Magdalena Geiser, Sabine Roesner, Monika Eckstein, Kilian Vomstein, Bettina Toth, Thomas Strowitzki, Tewes Wischmann, Beate Ditzen
HEALTH AND QUALITY OF LIFE OUTCOMES
(2022)
Article
Endocrinology & Metabolism
Ruben-J. Kuon, Kilian Vomstein
Summary: This article provides an overview of chronic endometritis (CE) in recurrent implantation failure and recurrent miscarriage, including its clinical symptoms, pathophysiology, diagnostics, and potential treatment options. Studies suggest that CE has negative effects on implantation and development in pregnancy. The gold standard for diagnosis is the immunohistochemical detection of CD138-positive plasma cells in endometrial biopsies. Successful treatment is achieved with antibiotics, resulting in improved implantation, pregnancy, and live birth rates. However, determining accurate diagnostic criteria and treating patients with persistent CE despite antibiotic treatment remain challenging.
GYNAKOLOGISCHE ENDOKRINOLOGIE
(2022)
Article
Obstetrics & Gynecology
Bettina Toth, Michael Bohlmann, Katharina Hancke, Ruben Kuon, Frank Nawroth, Soeren von Otte, Nina Rogenhofer, Sabine Rudnik-Schoeneborn, Ekkehard Schleussner, Clemens Tempfer, Kilian Vomstein, Tewes Wischmann, Michael von Wolff, Wolfgang Wuerfel, Johannes Zschocke
Summary: The purpose of this guideline is to standardize the diagnosis and therapy of recurrent miscarriage (RM) by using evidence from recent literature. The guideline provides consistent definitions, objective evaluations, and standardized treatment protocols. Recommendations are developed based on international literature, with special attention given to known risk factors and recommendations for cases with no abnormality found.
GEBURTSHILFE UND FRAUENHEILKUNDE
(2023)
Article
Obstetrics & Gynecology
Kilian Vomstein, Pia Egerup, Astrid Marie Kolte, Ida Behrendt-Moller, Amalie Dyhrberg Boje, Marie-Louise Bertelsen, Cecilie Sofie Eriken, Michelle Raupelyt Reierson, Bettina Toth, Nina la Cour Freiesleben, Henriette Svarre Nielsen
Summary: This study investigated the differences in menstrual blood lymphocytes between controls, patients with recurrent pregnancy loss (RPL), and patients with unexplained infertility (uINF). The results showed that RPL patients had significantly higher numbers of CD56+ NK cells in menstrual blood compared to controls, while both RPL and uINF patients had decreased numbers of CD56dimCD16bright NK cells in menstrual blood. These findings suggest altered cytotoxicity in menstrual blood NK cell subtypes of RPL and uINF patients compared to controls.
REPRODUCTIVE BIOMEDICINE ONLINE
(2023)
Article
Endocrinology & Metabolism
Jose M. Murrieta-Coxca, Emanuel Barth, Paulina Fuentes-Zacarias, Ruby N. Gutierrez-Samudio, Tanja Groten, Alexandra Gellhaus, Angela Koeninger, Manja Marz, Udo R. Markert, Diana M. Morales-Prieto
Summary: Placenta accreta spectrum (PAS) is a group of pathological conditions characterized by abnormal attachment of the placenta to the uterus wall, and it is a major cause of maternal morbidity and mortality worldwide. In this study, altered miRNA expression, particularly in placenta-specific miRNA clusters, was identified in placenta accreta tissue compared to normal placental tissues. Dysregulated pathways associated with cell cycle regulation, inflammation, and invasion were also observed. The study provides miRNA:mRNA associations that could contribute to our understanding of PAS development.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Orthopedics
Jasmin Bagge, Per Holmich, Freja Aabaek Hammer, Jan O. Nehlin, Kilian Vomstein, Lars Blond, Lisbet Rosenkrantz Holmich, Kristoffer Weisskirchner Barfod
Summary: This study aims to investigate the isolation and expansion of viable stem cells from cryopreserved microfragmented adipose tissue (AT) for the treatment of knee osteoarthritis. Stem cells were successfully recovered and expanded using both tissue explant culture (TEC) and enzymatic digestion (ED) methods. TEC provided more clinically relevant pericytes compared to ED.
JOURNAL OF EXPERIMENTAL ORTHOPAEDICS
(2023)
Article
Oncology
S. Loibl, H. A. Azim, T. Bachelot, P. Berveiller, A. Bosch, E. Cardonick, C. Denkert, M. J. Halaska, M. Hoeltzenbein, A. L. V. Johansson, C. Maggen, U. R. Markert, F. Peccatori, P. Poortmans, E. Saloustros, C. Saura, P. Schmid, E. Stamatakis, M. van den Heuvel-Eibrink, M. van Gerwen, V. Vandecaveye, G. Pentheroudakis, G. Curigliano, F. Amant
Summary: The management of breast cancer during pregnancy is a challenging area with limited evidence. In 2022, the European Society for Medical Oncology organized a virtual consensus-building process to address controversial issues and gain insights from experts in this field.
ANNALS OF ONCOLOGY
(2023)
Review
Immunology
Fernando Gomez-Chavez, Jose M. Murrieta-Goxes, Heriberto Caballero-Ortega, Diana M. Morales-Prieto, Udo R. Markert
Summary: Molecular communication between a pathogen and its host is crucial. Extracellular vesicles (EVs) act as mediators for the delivery of molecular signals. T. gondii infection during pregnancy can cause severe clinical complications. The role of EV signaling in this process remains unclear. This review summarizes the current knowledge on EV release from T. gondii and its human host cells regarding immunological consequences and placental passage.
JOURNAL OF REPRODUCTIVE IMMUNOLOGY
(2023)
Article
Endocrinology & Metabolism
Frantisek Staud, Xin Pan, Rona Karahoda, Xiaojing Dong, Petr Kastner, Hana Horackova, Veronika Vachalova, Udo R. Markert, Cilia Abad
Summary: This study reveals the crucial role of the placenta in regulating serotonin (5-HT) levels, including the clearance of 5-HT from the fetal circulation, its metabolism to 5-HIAA, and the subsequent excretion into the maternal circulation. This synchronized mechanism is critical for regulating 5-HT in the fetoplacental unit and can be compromised by external insults such as antidepressant drugs.
REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY
(2023)
Article
Obstetrics & Gynecology
Elizabeth Soczewski, Jose Martin Murrieta-Coxca, Lucas Miranda, Paulina Fuentes-Zacarias, Ruby Gutierrez-Samudio, Esteban Grasso, Marcelo Marti, Claudia Perez Leiros, Diana Morales-Prieto, Udo R. Markert, Rosanna Ramhorst
Summary: The study reveals the role of miRNAs in regulating endoplasmic reticulum stress and unfolded protein response in decidualized cells and endometrium associated with reproductive failures. The findings highlight the potential involvement of miR-17-5p, miR-21-5p, and miR-193b-3p in the regulation of ERS/UPR pathways and inflammation during embryo implantation. The expression of these miRNAs differs in stromal cells from patients with recurrent pregnancy loss and recurrent implantation failure, suggesting alterations in the regulation of ERS/UPR pathways.
REPRODUCTIVE BIOMEDICINE ONLINE
(2023)
Article
Medicine, General & Internal
Tine Wronding, Kilian Vomstein, Elleke F. Bosma, Brynjulf Mortensen, Henrik Westh, Julie Elm Heintz, Sarah Mollerup, Andreas Munk Petersen, Laura M. Ensign, Kevin DeLong, Johan E. T. van Hylckama Vlieg, Anne Bloch Thomsen, Henriette Svarre Nielsen
Summary: This article presents a proof of concept case study on vaginal microbiota transplantation (VMT) as a potential treatment for severe vaginal dysbiosis. The study successfully demonstrated a shift in the microbiome composition and resolution of symptoms after VMT, followed by a successful pregnancy and delivery. Larger studies are needed to further explore the efficacy of VMT.
Article
Obstetrics & Gynecology
Bettina Toth, Michael Bohlmann, Katharina Hancke, Ruben Kuon, Frank Nawroth, Soeren von Otte, Nina Rogenhofer, Sabine Rudnik-Schoeneborn, Ekkehard Schleussner, Clemens Tempfer, Kilian Vomstein, Tewes Wischmann, Michael von Wolff, Wolfgang Wuerfel, Johannes Zschocke
Summary: This guideline aims to standardize the diagnosis and therapy of recurrent miscarriage (RM) by using consistent definitions, objective evaluations, and standardized treatment protocols. The recommendations for diagnostic and therapeutic procedures are based on international literature, with special attention given to known risk factors and cases where no abnormalities are found.
GEBURTSHILFE UND FRAUENHEILKUNDE
(2023)