The Role of Sperm Proteins IZUMO1 and TMEM95 in Mammalian Fertilization: A Systematic Review

Gamete membrane fusion is a critical cellular event in sexual reproduction. In addition, the generation of knockout models has provided a powerful tool for testing the functional relevance of proteins thought to be involved in mammalian fertilization, suggesting IZUMO1 and TMEM95 (transmembrane protein 95) as essential proteins. However, the molecular mechanisms underlying the process remain largely unknown. Therefore, the aim of this study was to summarize the current knowledge about IZUMO1 and TMEM95 during mammalian fertilization. Hence, three distinct databases were consulted—PubMed, Scopus and Web of Science—using single keywords. As a result, a total of 429 articles were identified. Based on both inclusion and exclusion criteria, the final number of articles included in this study was 103. The results showed that IZUMO1 is mostly studied in rodents whereas TMEM95 is studied primarily in bovines. Despite the research, the topological localization of IZUMO1 remains controversial. IZUMO1 may be involved in organizing or stabilizing a multiprotein complex essential for the membrane fusion in which TMEM95 could act as a fusogen due to its possible interaction with IZUMO1. Overall, the expression of these two proteins is not sufficient for sperm–oocyte fusion; therefore, other molecules must be involved in the membrane fusion process.This research was funded by the Human Fertility Professorship and Departamento de Biotecnología of the Universidad de Alicante (VIGROB-186)

IZUMO1 Receptor Localization during Hyaluronic Acid Selection in Human Spermatozoa

IZUMO1 is an acrosome transmembrane protein implicated in the adhesion and fusion of gametes. This study aims to describe the distribution of IZUMO1 in human sperm under different physiological conditions: before capacitation (NCS), at one-hour capacitation (CS1), after a hyaluronic acid (HA) selection test (mature, MS1 and immature, IS1), and induced acrosome reaction from one-hour-capacitated sperm (ARS1). The data obtained in NCS, CS1, and MS1 significantly highlight dotted fluorescence in the acrosomal region (P1) as the major staining pattern (~70%). Moreover, we describe a new distribution pattern (P2) with a dotted acrosomal region and a labelled equatorial region that significantly increases in HA-bound spermatozoa, suggesting the onset of the migration of IZUMO1. In contrast, unbound spermatozoa presented an increase in P3 (equatorial region labelled) and P4 (not labelled). Finally, costaining to observe IZUMO1 distribution and acrosome status was performed in ARS1. Interestingly, we reported a variety of combinations between the IZUMO1 staining patterns and the acrosomal stages. In conclusion, these data show as a novelty the diffusion of the IZUMO1 protein during different physiological conditions that could contribute to the improvement in sperm selection techniques.This research was funded by Ministerio de Ciencia e Innovación (PID2021-123091NB-C22) and by Universidad de Alicante (VIGROB-186)

Elevated Lead, Nickel, and Bismuth Levels in the Peritoneal Fluid of a Peritoneal Endometriosis Patient without Toxic Habits or Occupational Exposure following a Vegetarian Diet

Potentially toxic elements (PTEs), found as environmental contaminants, have been related to endometriosis disease. In this context, the peritoneal fluid (PF) matrix has been poorly studied despite its importance. PF is the environment in which endometriotic lesions reside and communicate with surrounding tissues including tissues and nerve cells. In this work, our investigation group reports the special case of a peritoneal endometriosis patient presenting elevated lead, nickel, and bismuth levels in PF. This patient reported following a vegetarian diet and no toxic habits or occupational exposure. In conclusion, the elevated levels of PTEs found may result from a vegetarian diet or an unidentified environmental exposure source. This report provides new insights regarding the possible etiology of endometriosis disease and potential biomarkers for its diagnosis in early stages, although additional research is needed.This study was funded by the Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (UGP-19-042 and UGP-20-039). A.L.-B. is supported by the European Social Fund and the Generalitat Valenciana under a Ph.D. contract (ACIF–2021/243)

Development of an ICP-MS/MS-Based Methodology for the Analysis of (Ultra) Trace Elements in Follicular Fluid Samples of Patients Undergoing IVF Treatment

Introduction: The presence of heavy metals in the environment has been linked to female infertility. Follicular fluid (FF), which surrounds the developing oocyte in the ovary, can provide valuable insights into the content of a number of elements. However, there is a lack of comprehensive studies that analyze trace elements in FF samples using standardized protocols and methods. The objective of this study was to develop a reliable method utilizing ICP-MS/MS without sample digestion to detect 22 analytes in FF samples. Methods: Four FF samples (n = 4) were obtained from patients undergoing in vitro fertilization (IVF) treatments. These were adequately aliquoted and processed. They were subsequently analyzed via ICP-MS/MS, both in He and no-gas mode. Finally, the data of interest were compiled in a database. Results: Analyte recovery ranged from 70% to 130%, with better results observed in no-gas mode compared to He mode. Among the 22 elements analyzed, only 9Be, 140Ce, 111Cd, 139La, 208Pb, and 238U were not detected. Minor concentrations were observed for 137Ba, 209Bi, 59Co, 55Mn, 95Mo, 60Ni, 121Sb, 118Sn, 205Tl, and 51V, while intermediate concentrations were found for 7Li and 88Sr. Major concentrations were identified for 52Cr, 85Rb, 47Ti, and 66Zn. Conclusions: A new procedure was developed in this study, with several advantages. One of them is the good results in terms of the recovery of a wide variety of elements using ICP-MS/MS in the poorly studied biological matrix that is follicular fluid. Another advantage is the low amount of sample required to perform the analysis and the development of a green method where the sample is not digested and not diluted, which allowed us to avoid the excessive dilution of the concentration of analytes. Moreover, the developed method provides a novel approach to diagnose and predict health risks in women with gynecological pathologies and to assess their overall health, including reproductive health.This research was funded by the Human Fertility Chair of the University of Alicante

Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain : Large-Scale Epidemiological Study

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD-Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)-during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31-56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery

Correction : Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885

The authors wish to make the following corrections to this paper [...]

Quantification and Topographical Distribution of Terminal and Linked Fucose Residues in Human Spermatozoa by Using Field Emission Scanning Electron Microscopy (FE-SEM)

The modification of sperm glycocalyx is an essential process during sperm capacitation. The presence and redistribution of terminal and linked fucose have been described during in vitro capacitation in humans. However, the influence of the capacitation time on the quantification and localization of terminal and linked fucose is still unknown. In this study, the quantitative and qualitative changes in fucosyl residues during different in vitro capacitation times (1 and 4 h), are simultaneously characterized by using Aleuria aurantia (AAA) lectin–gold labelling and high-resolution field emission scanning electron microscopy (FE-SEM) in human sperm. A significant decrease was found in the number of terminal fucose registered in the whole sperm head during the in vitro capacitation. Nevertheless, the quantification of fucose residues after 1 h of in vitro capacitation was very similar to those found after 4 h. Therefore, the changes observed in terminal and linked fucose during capacitation were not time-dependent. Furthermore, the comprehensive analysis of the topographic distribution showed the preferential fucosyl location in the acrosomal region and the presence of distinct clusters distributed over the head in all the studied conditions. Overall, these findings corroborate the validity of FE-SEM combined with gold labelling to register changes in surface molecules during in vitro sperm capacitation.This research was funded by the Cátedra Human Fertility and Departamento de Biotecnología of the Universidad de Alicante (VIGROB-186)

Epigenetics Role in Spermatozoa Function: Implications in Health and Evolution&mdash;An Overview

The unique properties of spermatozoa are established through the spermatogenesis and maturation processes concurrently with its epigenome. It is known that damage to epigenetic mechanisms can lead to reproductive problems. However, scientific reviews addressing the role of the spermatozoa epigenome during the reproductive process are scarce. Therefore, the aim of this review was to offer a detailed overview of current knowledge in the field of spermatozoa epigenetics and its consequent implications. A full search was performed through three databases by combining five keywords. Inclusion criteria were implemented to grant accessibility, relevance, and concretion. Besides, some articles were manually removed or added to obtain an adequate and complete collection of 485 scientific publications. This compilation was used to conduct the bibliometric analysis and the data review separately. Bibliometric results displayed that spermatozoa epigenetics is an active and growing research area. The bibliographic overview showed that sperm epigenome correlates with the development of its function, explaining the environmental influence on reproductive pathologies or abnormal inheritance. The main conclusions were that the normal performance of sperm is heavily reliant on its epigenetics and that this study area is burgeoning, with the potential ability to provide society with clinical innovations in a short-term period

Epigenetics Role in Spermatozoa Function: Implications in Health and Evolution—An Overview

The unique properties of spermatozoa are established through the spermatogenesis and maturation processes concurrently with its epigenome. It is known that damage to epigenetic mechanisms can lead to reproductive problems. However, scientific reviews addressing the role of the spermatozoa epigenome during the reproductive process are scarce. Therefore, the aim of this review was to offer a detailed overview of current knowledge in the field of spermatozoa epigenetics and its consequent implications. A full search was performed through three databases by combining five keywords. Inclusion criteria were implemented to grant accessibility, relevance, and concretion. Besides, some articles were manually removed or added to obtain an adequate and complete collection of 485 scientific publications. This compilation was used to conduct the bibliometric analysis and the data review separately. Bibliometric results displayed that spermatozoa epigenetics is an active and growing research area. The bibliographic overview showed that sperm epigenome correlates with the development of its function, explaining the environmental influence on reproductive pathologies or abnormal inheritance. The main conclusions were that the normal performance of sperm is heavily reliant on its epigenetics and that this study area is burgeoning, with the potential ability to provide society with clinical innovations in a short-term period

Visual thinking y recursos audiovisuales cortos para fomentar la divulgación científica y la adquisición de conocimientos en Biología del Desarrollo: percepciones del alumnado

Las metodologías docentes activas ayudan al estudiantado a la adquisición de conocimientos mejorando el proceso de enseñanza-aprendizaje. En este trabajo, presentamos una experiencia de innovación educativa utilizando la herramienta didáctica visual thinking (VT) unida a la creación de recursos audiovisuales de divulgación científica con el fin de evaluar la percepción del alumnado sobre la utilidad de dicha herramienta para facilitar la adquisición de contenidos teóricos, fomentar la creatividad, el pensamiento crítico y el trabajo en equipo en la asignatura de Biología del Desarrollo. El colectivo estudiantil fue dividido en grupos y se les asignó una práctica de la asignatura a partir de la cual tuvieron que realizar una búsqueda bibliográfica de artículos científicos. Una vez seleccionados, el alumnado tuvo que realizar un mapa conceptual utilizando la herramienta VT y un vídeo divulgativo de 1 minuto de duración máxima a partir del contenido del VT. La percepción y valoración del estudiantado se obtuvo mediante un cuestionario de opinión previo y otro posterior a la experiencia. Los resultados de la percepción del alumnado sobre la metodología VT fueron que esta potenció la creatividad y el pensamiento crítico, y promovió un aprendizaje activo y significativo. La creación del material audiovisual también tuvo una gran acogida, ya que la adquisición del rol de divulgador científico fue muy bien evaluada por parte del alumnado