scholarly journals In vitro 3D Model of Female Reproductive Tract: An Overview and Future Aspect

Author(s):  
Arnaud Martino Capuzzo

Hormones must be balanced and dynamically controlled for the Female Reproductive Tract (FRT) to function correctly during the menstrual cycle, pregnancy, and delivery. Gamete selection and successful transfer to the uterus, where it implants and pregnancy occurs, is supported by the mucosal epithelial lining of the FRT ovaries, uterus, cervix, fallopian tubes, and vagina. Successful implantation and placentation in humans and other animals rely on complex interactions between the embryo and a receptive female reproductive system. The FRT's recent breakthroughs in three-dimensional (3D) organoid systems now provide critical experimental models that match the organ's physiological, functional, and anatomical characteristics in vitro. This article summarizes the current state of the art on organoids generated from various parts of the FRT. The current analysis examines recent developments in the creation of organoid models of reproductive organs, as well as their future directions.

2021 ◽  
Vol 99 (4) ◽  
pp. 531-553 ◽  
Author(s):  
Cindrilla Chumduri ◽  
Margherita Y. Turco

AbstractHealthy functioning of the female reproductive tract (FRT) depends on balanced and dynamic regulation by hormones during the menstrual cycle, pregnancy and childbirth. The mucosal epithelial lining of different regions of the FRT—ovaries, fallopian tubes, uterus, cervix and vagina—facilitates the selective transport of gametes and successful transfer of the zygote to the uterus where it implants and pregnancy takes place. It also prevents pathogen entry. Recent developments in three-dimensional (3D) organoid systems from the FRT now provide crucial experimental models that recapitulate the cellular heterogeneity and physiological, anatomical and functional properties of the organ in vitro. In this review, we summarise the state of the art on organoids generated from different regions of the FRT. We discuss the potential applications of these powerful in vitro models to study normal physiology, fertility, infections, diseases, drug discovery and personalised medicine.


2020 ◽  
Vol 28 (1) ◽  
pp. 35-51 ◽  
Author(s):  
Lama Alzamil ◽  
Konstantina Nikolakopoulou ◽  
Margherita Y. Turco

AbstractBoth the proper functioning of the female reproductive tract (FRT) and normal placental development are essential for women’s health, wellbeing, and pregnancy outcome. The study of the FRT in humans has been challenging due to limitations in the in vitro and in vivo tools available. Recent developments in 3D organoid technology that model the different regions of the FRT include organoids of the ovaries, fallopian tubes, endometrium and cervix, as well as placental trophoblast. These models are opening up new avenues to investigate the normal biology and pathology of the FRT. In this review, we discuss the advances, potential, and limitations of organoid cultures of the human FRT.


2009 ◽  
Vol 21 (9) ◽  
pp. 13
Author(s):  
G. Evans ◽  
S. P. De Graaf ◽  
W. M.C. Maxwell

The development and application of flow cytometric sorting for the pre-selection of sex has progressed at an increasing rate since the first report of live pre-sexed offspring of rabbits (2). The technique has been extended to production of pre-sexed offspring of numerous species and sorted bull semen is now widely available commercially around the world. Due to the stresses involved in the sex-sorting process, sex-sorted sperm may be functionally compromised in terms of reduced motility and viability, and their fertilising lifespan within the female reproductive tract may be reduced. Consequently, fertility in vivo may be compromised. However, improvements to the technology and a greater understanding of its biological impact on the sperm have facilitated recent developments in sheep, and we have demonstrated that sex-sorting is capable of selecting a functionally superior ram sperm population in terms of both in vitro and in vivo function. This has resulted in high fertility after intrauterine insemination of sex-sorted ram sperm (1). Unfortunately, to date, these results have not been matched in other species.


2011 ◽  
Vol 23 (8) ◽  
pp. 976 ◽  
Author(s):  
Mark Burkitt ◽  
Dawn Walker ◽  
Daniela M. Romano ◽  
Alireza Fazeli

Understanding the complex interactions between gametes, embryos and the maternal tract is required knowledge for combating infertility and developing new methods of contraception. Here we present some main aspects of spermatozoa interactions with the mammalian oviduct before fertilisation and discuss how computational modelling can be used as an invaluable aid to experimental investigation in this field. A complete predictive computational model of gamete and embryo interactions with the female reproductive tract is a long way off. However, the enormity of this task should not discourage us from working towards it. Computational modelling allows us to investigate aspects of maternal communication with gametes and embryos, which are financially, ethically or practically difficult to look at experimentally. In silico models of maternal communication with gametes and embryos can be used as tools to complement in vivo experiments, in the same way as in vitro and in situ models.


Author(s):  
Ruben Heremans ◽  
Ziga Jan ◽  
Dirk Timmerman ◽  
Hugo Vankelecom

The pelviperineal organs of the female reproductive tract form an essential cornerstone of human procreation. The system comprises the ectodermal external genitalia, the Müllerian upper-vaginal, cervical, endometrial and oviductal derivatives, and the endodermal ovaries. Each of these organs presents with a unique course of biological development as well as of malignant degeneration. For many decades, various preclinical in vitro models have been employed to study female reproductive organ (patho-)biology, however, facing important shortcomings of limited expandability, loss of representativeness and inadequate translatability to the clinic. The recent emergence of 3D organoid models has propelled the field forward by generating powerful research tools that in vitro replicate healthy as well as diseased human tissues and are amenable to state-of-the-art experimental interventions. Here, we in detail review organoid modeling of the different female reproductive organs from healthy and tumorigenic backgrounds, and project perspectives for both scientists and clinicians.


Author(s):  
Mai M. Said ◽  
Ramesh K. Nayak ◽  
Randall E. McCoy

Burgos and Wislocki described changes in the mucosa of the guinea pig uterus, cervix and vagina during the estrous cycle investigated by transmission electron microscopy. More recently, Moghissi and Reame reported the effects of progestational agents on the human female reproductive tract. They found drooping and shortening of cilia in norgestrel and norethindrone- treated endometria. To the best of our knowledge, no studies concerning the effects of mestranol and norethindrone given concurrently on the three-dimensional surface features on the uterine mucosa of the guinea pig have been reported. The purpose of this study was to determine the effect of mestranol and norethindrone on surface ultrastructure of guinea pig uterus by SEM.Seventy eight animals were used in this study. They were allocated into two groups. Group 1 (20 animals) was injected intramuscularly 0.1 ml vegetable oil and served as controls.


2018 ◽  
Vol 18 (4) ◽  
pp. 246-255 ◽  
Author(s):  
Lara Termini ◽  
Enrique Boccardo

In vitro culture of primary or established cell lines is one of the leading techniques in many areas of basic biological research. The use of pure or highly enriched cultures of specific cell types obtained from different tissues and genetics backgrounds has greatly contributed to our current understanding of normal and pathological cellular processes. Cells in culture are easily propagated generating an almost endless source of material for experimentation. Besides, they can be manipulated to achieve gene silencing, gene overexpression and genome editing turning possible the dissection of specific gene functions and signaling pathways. However, monolayer and suspension cultures of cells do not reproduce the cell type diversity, cell-cell contacts, cell-matrix interactions and differentiation pathways typical of the three-dimensional environment of tissues and organs from where they were originated. Therefore, different experimental animal models have been developed and applied to address these and other complex issues in vivo. However, these systems are costly and time consuming. Most importantly the use of animals in scientific research poses moral and ethical concerns facing a steadily increasing opposition from different sectors of the society. Therefore, there is an urgent need for the development of alternative in vitro experimental models that accurately reproduce the events observed in vivo to reduce the use of animals. Organotypic cultures combine the flexibility of traditional culture systems with the possibility of culturing different cell types in a 3D environment that reproduces both the structure and the physiology of the parental organ. Here we present a summarized description of the use of epithelial organotypic for the study of skin physiology, human papillomavirus biology and associated tumorigenesis.


Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 460
Author(s):  
Beatriz Medeiros-Fonseca ◽  
Antonio Cubilla ◽  
Haissa Brito ◽  
Tânia Martins ◽  
Rui Medeiros ◽  
...  

Penile cancer is an uncommon malignancy that occurs most frequently in developing countries. Two pathways for penile carcinogenesis are currently recognized: one driven by human papillomavirus (HPV) infection and another HPV-independent route, associated with chronic inflammation. Progress on the clinical management of this disease has been slow, partly due to the lack of preclinical models for translational research. However, exciting recent developments are changing this landscape, with new in vitro and in vivo models becoming available. These include mouse models for HPV+ and HPV− penile cancer and multiple cell lines representing HPV− lesions. The present review addresses these new advances, summarizing available models, comparing their characteristics and potential uses and discussing areas that require further improvement. Recent breakthroughs achieved using these models are also discussed, particularly those developments pertaining to HPV-driven cancer. Two key aspects that still require improvement are the establishment of cell lines that can represent HPV+ penile carcinomas and the development of mouse models to study metastatic disease. Overall, the growing array of in vitro and in vivo models for penile cancer provides new and useful tools for researchers in the field and is expected to accelerate pre-clinical research on this disease.


Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3088
Author(s):  
Mariana Matias ◽  
Jacinta O. Pinho ◽  
Maria João Penetra ◽  
Gonçalo Campos ◽  
Catarina Pinto Reis ◽  
...  

Melanoma is recognized as the most dangerous type of skin cancer, with high mortality and resistance to currently used treatments. To overcome the limitations of the available therapeutic options, the discovery and development of new, more effective, and safer therapies is required. In this review, the different research steps involved in the process of antimelanoma drug evaluation and selection are explored, including information regarding in silico, in vitro, and in vivo experiments, as well as clinical trial phases. Details are given about the most used cell lines and assays to perform both two- and three-dimensional in vitro screening of drug candidates towards melanoma. For in vivo studies, murine models are, undoubtedly, the most widely used for assessing the therapeutic potential of new compounds and to study the underlying mechanisms of action. Here, the main melanoma murine models are described as well as other animal species. A section is dedicated to ongoing clinical studies, demonstrating the wide interest and successful efforts devoted to melanoma therapy, in particular at advanced stages of the disease, and a final section includes some considerations regarding approval for marketing by regulatory agencies. Overall, considerable commitment is being directed to the continuous development of optimized experimental models, important for the understanding of melanoma biology and for the evaluation and validation of novel therapeutic strategies.


2021 ◽  
Vol 8 ◽  
Author(s):  
Eduardo G. Aisen ◽  
Wilfredo Huanca López ◽  
Manuel G. Pérez Durand ◽  
Edita Torres Mamani ◽  
Juan C. Villanueva Mori ◽  
...  

The viscous seminal plasma (SP) is currently a major impediment to the handling of ejaculate and the development of some biotechnologies in South American camelids. The vas deferens-collected spermatozoa of alpacas is a useful technique to avoid this problem. On the other hand, SP contains a large protein component that has been implicated in the function of spermatozoa within the female reproductive tract. In this sense, the low fertility achieved using transcervical insemination with frozen-thawed spermatozoa in alpacas could be improved by adding SP. This study aimed to evaluate the effect of the whole SP on some in vitro parameters of alpaca spermatozoa after the freezing-thawing-process and the fertility after artificial insemination. It would contribute to a better understanding of the interaction between thawed sperm cells and SP. Spermatozoa were obtained by surgically diverted vas deferens. The samples were diluted with a Tris-based extender, packaged in straws, and frozen. At thawing, each straw was divided into two post-thawing conditions: with the addition of 10% of PBS (control) or with 10% SP (treatment). The sperm cells were evaluated using dynamic parameters, sperm cell morphology, and morphometry. Fertility was assessed by an artificial insemination trial. All in vitro parameters were analyzed by ANOVA. A heterogeneity test was scheduled for the fertility trial. After the freezing-thawing process, motility and plasma membrane functionality was improved when SP was added. No differences were found for post-thaw viability between the control and treatment samples. The percentage of normal cells was higher with SP at post-thawing, and a decrease of the presence of bent tailed spermatozoa with a droplet in the SP group was observed. The length of the head spermatozoa was 3.4% higher in the samples with PBS compared to those in which SP was added. Females pregnant at day 25 post-insemination were 0/12 (with SP inside the straw) and 1/10 (without SP inside the straw). In conclusion, the presence of 10% SP at post-thawing improves sperm cells' motility, functionality, and morphology, indicating that it would be beneficial to improve the frozen-thawed alpaca's physiology spermatozoa. More fertility trials must be developed to increase this knowledge.


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