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2. From a passive conduit to highly dynamic organ - what are the roles of uterine tube epithelium in reproduction?

Creator:
Csöbönyeiová, Mária, Varga, Ivan, Lapides, Lenka, Pavlíková, Lada, Feitscherová, Claudia, and Klein, Martin
Format:
počítač and online zdroj
Type:
model:article and TEXT
Subject:
embryo, epithelium, fertilization, immune system, spermatozoa, tubal fluid, and uterine tube
Language:
English
Description:
It is well known that the mammalian uterine tube (UT) plays a crucial role in female fertility, where the most important events leading to successful fertilization and pre-implantation embryo development occur. The known functions of these small intraabdominal organs are: an uptake and transport of oocytes; storage, transportation, and capacitation of spermatozoa, and finally fertilization and transport of the fertilized ovum and early embryo through the isthmus towards the uterotubal junction. The success of all these events depends on the interaction between the uterine tube epithelium (UTE) and gametes/embryo. Besides that, contemporary research revealed that the tubal epithelium provides essential nutritional support and the most suitable environment for early embryo development. Moreover, recent discoveries in molecular biology help understand the role of the epithelium at the cellular and molecular levels, highlighting the factors involved in regulating the UT signaling, that affects different steps in the fertilization process. According to the latest research, the extracellular vesicles, as a major component of tubal secretion, mediate the interaction between gametes/embryo and epithelium. This review aims to provide up-to-date knowledge on various aspects concerning tubal epithelium activity and its cross-talk with spermatozoa, oocytes and preimplantation embryo and how these interactions affect fertilization and early embryo development.
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

3. Functional morphology of the human uterine tubes in the 21st century: anatomical novelties and their possible clinical applications

Creator:
Varga, Ivan, Csöbönyeiová, Mária, Visnyaiová, Kristína, Záhumenský, Jozef, Pavlíková, Lada, Feitscherová, Claudia, and Klein, Martin
Format:
počítač and online zdroj
Type:
model:article and TEXT
Subject:
uterine tube, uterine tube functions, tubal telocytes, tubal lymphatic lacunae, tubal immune cell repertoire, high-gradeserous ovarian cancers, and tubal cell cultures and organoids
Language:
English
Description:
The uterine tube (UT) pathologies account for 25-35 % of female factor infertility. Although these peculiar organs were first studied several hundred years ago, they have become overlooked and neglected mainly due to the successes of reproductive medicine. Nevertheless, reproductive medicine still faces many challenges regarding the fertility outcomes of in vitro fertilization (IVF). Many obstacles and problems can be resolved by a more detailed understanding of the UT morphology and function during normal reproduction. Over the course of the 21st century, many new insights have been obtained: the presence of a population of telocytes in the tubal wall responsible for normal motility and hormone sensory function, the demonstration of lymphatic lacunae of the mucosal folds necessary for oocyte capture and tubal fluid recirculation, or a thorough profiling of the immune makeup of the UT epithelial lining with the discovery of regulatory T cells presumably important for maternal tolerance towards the semiallogenic embryo. New discoveries also include the notion that the UT epithelium is male sex hormone-sensitive, and that the UT is not sterile, but harbors a complex microbiome. The UT epithelial cells were also shown to be the cells-of-origin of high-grade serous ovarian carcinomas. Finally, yet importantly, several modern morphological directions have been emerging recently, including cell culture, the development of tubal organoids, in silico modelling, tissue engineering and regenerative medicine. All these novel insights and new approaches can contribute to better clinical practice and successful pregnancy outcomes.
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

4. Immunohistochemical and scanning electron microscopic confirmation of the lymphatic lacunae in the uterine tube mucosal folds. What are the clinical implications?

Creator:
Csöbönyeiová, Mária, Klein, Martin, Juríková, Miroslava, Feitscherová, Claudia, Gálfiová, Paulína, and Varga, Ivan
Format:
počítač and online zdroj
Type:
model:article and TEXT
Subject:
uterine tube, Lymphatic lacunae, immunohistochemistry, D2-40, podoplanin, VEGFR-3, and SEM
Language:
English
Description:
Uterine tubes (UTs) are essential during physiological reproduction. The most intriguing part of its wall is the mucosa. Apart from the epithelial cells vital for its normal function, the connective tissue lamina propria contains wide spaces whose function, morphology and structure are yet to be elucidated. The present study used bioptic samples from 25 premenopausal (mean age 48.3 years, σ=3.56) and 25 postmenopausal women (mean age 57.8 years, σ=7.79). In both study groups, samples were obtained from two anatomically distinct parts of the UT – ampulla and infundibulum with fimbriae. The specimens were processed for scanning electron microscopy (SEM) and immunohistochemical detection of podoplanin (clone D2-40) and VEGFR-3 – two markers of lymphatic endothelial cells. The results showed that specimens from premenopausal and postmenopausal women contain wide lymphatic spaces, also known as lymphatic lacunae. The most probable function of the lacunae in the fimbriae is oocyte pick-up upon ovulation thanks to their ability to get engorged with lymph, thus serving as an erectile-like tissue. The ampullary lacunae are probably responsible for tubal fluid maintenance and recirculation. These results indicate that they are vital for normal reproduction because tubal fluid dynamics are as important as fluid composition. Further research on this topic is highly warranted because more detailed insights into UT function have a great potential to refine the methods of reproductive medicine, e.g. in vitro fertilization (IVF), which are still far from optimal regarding fertility outcomes.
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

5. Is there a need to change the basic principles of histology? Educational, functional and embryological perspective

Creator:
Varga, Ivan, Kachlík, David, Csöbönyeiová, Mária, Feitscherová, Claudia, and Klein, Martin
Format:
počítač and online zdroj
Type:
model:article and TEXT
Subject:
classification, education, four tissue types, and Terminologia Histologica
Language:
English
Description:
Although it is not an easy task to classify cells into different types, or in turn cell types into tissue types, a clear, understandable, didactically and clinically relevant tissue classification is indispensable for undergraduate medical education, expert discussions in biomedical research as well as for clinical practice. From the earliest discovery of the light microscope on, tissue classification has been a dynamic process. Historically, it was not a rare occurrence that different textbooks offered different tissue classifications. Nowadays, classifications have almost become uniform – the most common is the histological classification into four basic tissue types (epithelial, connective, muscle, nervous), which is recognized by the majority of modern histology and pathology textbooks. The reason is that, with some exceptions, this classification seems to be the most relevant not only for educational purposes but also from an embryological perspective and clinical-histopathological practice. Recently, attempts have been made to abandon this established classification and replace it with a new one. Any new classification, which would improve the presently used is welcomed. However, if the proposed innovation does not satisfy the needs of modern education and clinical practice, it should be handled with great caution or reconsidered.
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

6. Our first experience implementing “clinical embryology and reproductive medicine” as a curriculum course of the Study Program General Medicine at the Faculty of Medicine in Bratislava, Slovakia

Creator:
Varga, Ivan, Lapides, Lenka, Brucknerová, Ingrid, Gálfiová, Paulína, Visnyaiová, Kristína, Csöbönyeiová, Mária, Klein, Martin, Žiaran, Stanislav, Sysák, Rastislav, and Záhumenský, Jozef
Format:
počítač and online zdroj
Type:
model:article and TEXT
Subject:
assisted reproduction, clinical embryology, congenital malformations, infertility, prenatal diagnosis, and reproductive immunology and endocrinology
Language:
English
Description:
There is no separate course in the medical curriculum summarizing all aspects of human reproduction in most medical school curricula. At the same time, such a course would logically connect knowledge from clinical embryology and assisted reproduction, encompassing the issue of female and male infertility, mechanisms of birth defect formation, their prenatal diagnosis and subsequent specialized neonatal care. The aim of a wide team of university teachers comprising embryologists, gynecologists, neonatologists, endocrinologists, geneticists and others was to create and implement a new course entitled "Clinical Embryology and Reproductive Medicine" into the fourth-year curriculum of the study program General Medicine at the Faculty of Medicine, Comenius University in Bratislava. There has been a great interest in the course, as evidenced by the number of medical students enrolled. The lecture syllabuses have been divided into several thematic areas: 1) Clinical embryology including a laboratory part of assisted reproduction, 2) Cause and treatment options of female and male infertility, 3) A comprehensive view of the issue of birth defects, 4) The issue of preconception education, prenatal and childbirth training, family planning, 5) Reproductive immunology and endocrinology. Despite the complexity of human reproduction being a mainstay of gynecology and obstetrics, it is underemphasized in the medical school curricula worldwide. It is often reflected in shorter hospital / practical trainings during undergraduate studies and lower requirements at the final exam. Therefore, as students almost unanimously valued, this new course is extremely helpful in preparing for the final state exam.
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

7. Scanning electron microscopic study of the human uterine tube epithelial lining: surgical biopsy samples and epithelial cell culture

Creator:
Gálfiová, Paulína, Polák, Štefan, Mikušová, Renáta, Juríková, Miroslava, Klein, Martin, Csöbönyeiová, Mária, Danišovič, Ľuboš, and Varga, Ivan
Format:
počítač and online zdroj
Type:
model:article and TEXT
Subject:
uterine/fallopian tube epithelium, ultrastructure, scanning electron microscopy, and fallopian tube epithelial cell in vitro culture
Language:
English
Description:
This article summarizes the importance of the exact morphology of human uterine/fallopian tube epithelium at the scanning electron microscopy (SEM) level for the clinical outcome even nowadays. Visual referential micrographs from SEM reflect two ways to view human epithelial cell lining surfaces: the surface epithelial uterine tube from surgical tissue biopsy and human fallopian tube epithelial cells (HFTEC) culture monolayer surface. One colorized image visualizes ciliated cells, distinguishes them from non-ciliated cells, and provides an educational benefit. A detailed description of the ultrastructure in referential and pathologic human uterine tube epithelium is important in defining the morphological basis of high-grade carcinomas, in the mechanism of pathophysiology, and in discussing options for its prevention. Cell cultures of human fallopian tube epithelial cells offer new approaches in simulating the mechanisms of cancer genesis or may help to elucidate the genetic basis of several diagnoses. New technical approaches in SEM provide higher resolution and detailed surface images. The SEM modality is still one of the current options in diagnostics and may be useful for advancing human reproductive organ cancer research.
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

8. The overview of anatomical variations and congenital anomalies of the uterine tubes and their impact on fertility

Creator:
Csöbönyeiová, Mária, Klein, Martin, Feitscherová, Claudia, Pavlíková, Lada, Kachlík, David, and Varga, Ivan
Format:
počítač and online zdroj
Type:
model:article and TEXT
Subject:
anatomical variations, congenital anomalies, uterine tube, fertility, agenesis, accessory uterine tube, accessory ostium, paratubal cysts, and terminological discrepancies
Language:
English
Description:
Anatomical variations and congenital anomalies of the uterine tubes (UTAVsCAs) are rare conditions, which are often undiagnosed, or accidentally diagnosed upon imaging, laparotomy, laparoscopy for unrelated condition, or during the Cesarean section. UTAVsCAs are often asymptomatic, but their clinical relevance lies in their possibly adverse impact on fertility. Since their rare occurrence, they are usually published as case reports. The most typically described are: agenesis of the uterine tubes (UTs), accessory UT (UT duplication), accessory UT ostium, and paratubal cysts (e.g. the hydatid cyst of Morgagni). UTAVsCAs are classified into an umbrella category of Müllerian duct anomalies (MDAs) which comprises anomalous development of all the organs developing from the paramesonephric (Müllerian) ducts, i.e., UTs, uterus and upper portion of the vagina. Interestingly, most of the classification systems of MDAs discuss solely the uterine and vaginal anomalies, while the UTs are often utterly ignored. This probably originates from the fact that UTs are no longer interesting for many clinicians as they think of UTs as superfluous organs whose function can be easily replaced in the in vitro fertilization (IVF) laboratory. Indeed, the modern reproductive medicine has been helping enormously with the conception of infertile couples. In many instances, the UTs are in fact successfully bypassed and a “test-tube” baby is born. Nevertheless, the UTs are still absolutely unique in providing suitable environment for fertilization and early embryo development - processes that has not been still completely understood. This fact could partially explain why the success rate of IVF is “only” around 30-50 % depending on age. Therefore, the research of the UTAVsCAs is still clinically relevant in the context of reproductive medicine and should not be omitted from research endeavors.
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

9. Uterine Natural Killer cells in context of implantation: immunohistochemical analysis of endometrial samples from women with habitual abortion and recurrent implantation failure

Creator:
Lapides, Lenka, Klein, Martin, Belušáková, Viera, Csöbönyeiová, Mária, Varga, Ivan, and Babál, Pavel
Format:
počítač and online zdroj
Type:
model:article and TEXT
Subject:
uterine NK cells, recurrent implantation failure, habitual abortion, immunohistochemistry, and CD56
Language:
English
Description:
Infertility affects approximately 48 million couples globally. Despite the enormous progress of the methods of reproductive medicine that has been made since the first test-tube baby was born in 1978, the implantation rate of day-3 embryos is only around 15-20 % and 30 % of day-5 embryos. Numerous strategies aim to improve implantation rates and prevent repeated implantation failure. However, there is no specific general recommendation leading to satisfying results. One of the many risk factors relevant in this regard is the uterine immunological make-up, mainly the uterine Natural Killer (uNK) cells. They orchestrate the overall immune response during implantation by influencing trophoblast invasion and vascular remodeling and throughout pregnancy, uNK cells are also the main immune cells at the maternal–fetal interface. Previously, uNK count has been correlated with various fertility issues including idiopathic recurrent miscarriage. The present study used endometrial samples collected from 256 patients with recurrent implantation failure (RIF), habitual abortion (HA) and idiopathic sterility. Samples were collected between day 19 and 21 of the menstrual cycle mainly by Pipelle endometrial sampling. The samples were fixed in formalin for 24 hours and further processed for immunohistochemistry using anti-CD56 to visualize this antigen marker of uNK cells. Immunohistochemical counting was performed to assess the low, normal, or elevated count of uNK cells. According to the one-way ANOVA test, the age of our patients did not have any influence on the count of uNK cells. With Spearman correlation analysis, we found statistically significant correlation (p-value 0.05) of -0.133 between prior miscarriage and lower uNK cell count. Using the same analysis we found statistically significant correlation (correlation 0.233 with p-value 0.01) between number of uNK cells and activation status. Patients with higher uNK cells were more frequenty diagnosed with endometriosis (p-value 0.05, correlation 0.130). Patients with an immunological factor of sterility (defined by a clinical immunologist) had a lower chance of gravidity (-0.203 with p-value 0.01). Based on our results, we can confirm that there is a correlation between RIF, HA, idiopathic sterility, endometriosis, and immunological factor of sterility (uNK cell count). The true predictive value with regard to fertility outcomes needs to be addressed in future research.
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

10. When less is more - pipelle endometrial sampling for quantification of uterine natural killer cells in patients with recurrent implantation failure or habitual abortion

Creator:
Lapides, Lenka, Varga, Ivan, Klein, Martin, Rybánska, Lenka, Belušáková, Viera, and Babál, Pavel
Format:
počítač and online zdroj
Type:
model:article and TEXT
Subject:
endometrium, uterine NK cells, recurrent implantation failure, habitual abortion, pipelle endometrial sampling, and curettage
Language:
English
Description:
Despite recent advancements in reproductive medicine, recurrent implantation failure and habitual abortion remain ongoing issues. One of the most important aspects of successful implantation is the intricate immune response and regulation necessary for the acceptance of the hemiallogenic embryo. The most numerous immune cells in the decidua are uterine natural killer cells (uNK). Studies suggest that changes in the uNK count and physiology may be responsible for the aforementioned pathological conditions. Thus, testing for uNK may provide valuable insights into their pathogenesis. The study compared Pipelle endometrial sampling with conventional curettage to find out whether the less invasive Pipelle method is a viable alternative of tissue collection. Tissue samples from 14 patients obtained by both methods were examined. The average size of tissue samples obtained with Pipelle was 17 mm2 , samples obtained with curettage had on average 34 mm2 . Using immunohistochemical visualization of CD56 (NK cells) and granzyme B antigens (serine protease-expressing activation state of NK cells), it was found that the average total count of CD56 / mm2 was 115 for Pipelle and 120 for curettage, respectively. The study also proved a correlation between granzyme B positivity and identification of NK cells clusters. The results indicated that Pipelle endometrial sampling seems a suitable method of tissue harvesting for the purpose of uNK cells examination. Pipelle endometrial sampling is safe, cost-effective and can be performed on an outpatient basis without the need of anesthesia or analgesia. Several issues remain yet to be solved: how to standardize the subsequent uNK testing, how to interpret the results and finally yet importantly, how to use this knowledge in personalized treatment protocols.
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public