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Ethnopharmacological Relevance: Ethnopharmacological studies for drug discovery from natural compounds play an important role for developing current therapeutical platforms. Plants are a group of natural sources which have been served as the basis in the treatment of many diseases for centuries. In this regard, Ceratonia siliqua (carob) is one of the herbal medicine which is traditionally used for male infertility treatments. But so far the main mechanisms for effects of carob are unknown. Here, we intend to investigate the ability of carob extract to induce spermatogenesis in an azoospermia mouse model and determine the mechanisms that underlie its function., Aim of the Study: This is a pre-clinical animal model study to evaluate the effect of carob extract in spermatogenesis recovery., Methods: We established an infertile mouse model with the intent to examine the ability of carob extract as a potential herbal medicine for restoration of male fertility. Sperm parameters, as well as gene expression dynamics and levels of spermatogenesis hormones, were evaluated 35 days after carob administration., Results: Significant enhanced sperm parameters (P < 0.05) showed that the carob extract could induce spermatogenesis in the infertile mouse model. Our data suggested an anti-apototic and inducer role in the expressions of cell cycle regulating genes. Carob extract improved the spermatogenesis niche by considerable affecting Sertoli and Leydig cells (P < 0.05). The carob-treated mice were fertile and contributed to healthy offspring that matured. Our data confirmed that this extract triggered the hormonal system, the spermatogenesis-related gene expression network, and signaling pathways to induce and promote sperm production with notable level (P < 0.05). We found that the aqueous extract consisted of a polar and mainly well water-soluble substance. Carob extract might upregulate spermatogenesis hormones via its amino acid components, which were detected in the extract by liquid chromatography-mass spectrometry (LC-MS)., Conclusion: Our results strongly suggest that carob extract might be a promising future treatment option for male infertility. This finding could pave the way for clinical trials in infertile men. This is the first study that has provided reliable, strong pre-clinical evidence for carob extract as an effective candidate for fertility recovery in cancer-related azoospermia., Competing Interests: Declaration of competing interest The authors declare that they do not have any conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Demystifying the mechanisms that underlie germline development and gamete production is critical for expanding advanced therapies for infertile couples who cannot benefit from current infertility treatments. However, the low number of germ cells, particularly in the early stages of development, represents a serious challenge in obtaining sufficient materials required for research purposes. In this regard, pluripotent stem cells (PSCs) have provided an opportunity for producing an unlimited source of germ cells in vitro. Achieving this ambition is highly dependent on accurate stem cell niche reconstitution which is achievable through applying advanced cell engineering approaches. Recently, hydrogel microparticles (HMPs), as either microcarriers or microcapsules, have shown promising potential in providing an excellent 3-dimensional (3D) biomimetic microenvironment alongside the systematic bioactive agent delivery. In this review, recent studies of utilizing various HMP-based cell engineering strategies for appropriate niche reconstitution and efficient in vitro differentiation are highlighted with a special focus on the capabilities of droplet-based microfluidic (DBM) technology. We believe that a deep understanding of the current limitations and potentials of the DBM systems in integration with stem cell biology provides a bright future for germ cell research., Supplementary Information: The online version contains supplementary material available at 10.1007/s12551-021-00907-5., Competing Interests: Conflict of interestThe authors declare no competing interests., (© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2021.)

Recent developments in organoid technology are revolutionizing our knowledge about the biology, physiology, and function of various organs. Female reproductive biology and medicine also benefit from this technology. Organoids recapitulate features of different reproductive organs including the uterus, fallopian tubes, and ovaries, as well as trophoblasts. The genetic stability of organoids and long-lasting commitment to their tissue of origin during long-term culture makes them attractive substitutes for animal and in vitro models. Despite current limitations, organoids offer a promising platform to address fundamental questions regarding the reproductive system's physiology and pathology. They provide a human source to harness stem cells for regenerative medicine, heal damaged epithelia in specific diseases, and study biological processes in healthy and pathological conditions. The combination of male and female reproductive organoids with other technologies, such as microfluidics technology, would enable scientists to create a multi-organoid-on-a-chip platform for the next step to human-on-a-chip platforms for clinical applications, drug discovery, and toxicology studies. The present review discusses recent advances in producing organoid models of reproductive organs and highlights their applications, as well as technical challenges and future directions.

Comprehensively understanding the female reproductive system is crucial for safeguarding fertility and preventing diseases concerning women's health. With the capacity to simulate the intricate physio- and patho-conditions, and provide diagnostic platforms, microfluidic chips have fundamentally transformed the knowledge and management of female reproductive health, which will ultimately promote the development of more effective assisted reproductive technologies, treatments, and drug screening approaches. This review elucidates diverse microfluidic systems in mimicking the ovary, fallopian tube, uterus, placenta and cervix, and we delve into the culture of follicles and oocytes, gametes' manipulation, cryopreservation, and permeability especially. We investigate the role of microfluidics in endometriosis and hysteromyoma, and explore their applications in ovarian cancer, endometrial cancer and cervical cancer. At last, the current status of assisted reproductive technology and integrated microfluidic devices are introduced briefly. Through delineating the multifarious advantages and challenges of the microfluidic technology, we chart a definitive course for future research in the woman health field. As the microfluidic technology continues to evolve and advance, it holds great promise for revolutionizing the diagnosis and treatment of female reproductive health issues, thus propelling us into a future where we can ultimately optimize the overall wellbeing and health of women everywhere. [ABSTRACT FROM AUTHOR]

Scientists have been interested in human reproduction for a long time, since on the one hand, it is related to human life, and on the other hand, it ensures the transmission of genetic traits from parents to children, as low fertility is considered one of the social problems leading to psychological disorders in couples who are unable to have children or what is called infertile. Therefore, this study aimed to find out the protective effects of the alcoholic extract of ginseng roots and carob fruits on the level of oxidative balance in semen and improving reproductive efficiency by examining the histological parameters of testes in albino male rabbits, and comparing these effects with the effects of vitamin E known for its antioxidant properties. This study included using forty adult albino male rabbits in eight groups, with five rabbits in each group and convergent weights. All groups were fed a standard diet throughout the five-month experimental period. The treatments were as follows: The first group (T1) were gavaged by distilled water, the second (T2) by 200 mg kg-1 alcoholic extract of ginseng roots, the third (T3) by 400 mg kg-1 alcoholic extract of ginseng roots, the fourth (T4) by 200 mg kg-1 alcoholic extract of carob fruits, the fifth (T5) by 400 mg kg-1 alcoholic extract of carob fruits, the sixth (T6) by 100 mg kg-1 alcoholic extract of ginseng roots + 100 mg kg-1 carob fruits, the seventh (T7) by 200 mg kg-1 alcoholic extract of ginseng roots + 200 mg kg-1 carob fruits, and finally, the eighth (T8) by 400 mg kg-1 vitamin E. Our results showed a significant drop (p < 0.05) in the level of MDA concentration and a significant upraise in the level of CAT, GSH and TAC concentration in the semen. The results also revealed the normal shape of the seminiferous tubules and an improvement in reproductive efficiency through the elevation in spermatogenesis percentage (SP), primary spermatocytes percentage (PSP), secondary spermatocytes percentage (SSP), spermatozoa percentage (SpP) and mature sperm percentage (MSP) for groups dosed by ginseng root extract + carob fruits and by vitamin E compared to the normal control group. Ginseng roots extract at a dose of 200 mg kg-1 + carob fruits at a dose of 200 mg kg-1 (T7) were superior to all treatments, followed by vitamin E (T8). Thus, we concluded from the current study that the effect of T7 reduces the level of free radicals and raises the level of antioxidants in the semen, and increases reproductive efficiency through the high percentage of sperm in the semen. [ABSTRACT FROM AUTHOR]

The carob tree (Ceratonia siliqua L.) is currently considered one of the most valuable fruit and forest trees in various fields and sectors of activity. It is a versatile plant, belonging to the Fabaceae family. It is widely used in traditional medicine to treat many diseases such as diabetes, hypertension, and gastrointestinal disorders, given that all its parts (leaves, flowers, pods, seeds, wood, bark, and roots) are useful and hold value in many areas. Its importance has increased significantly in recent years. Originating from the Middle East, it is recognized for its ecological and industrial significance. Previous studies conducted on Ceratonia siliqua L. have revealed the presence of several compounds, including polyphenols, flavonoids, carbohydrates, minerals, and proteins. The carob tree demonstrates antihypertensive, antidepressant, anti-obesity, and antihyperglycemic activities. This plant is known for its medicinal and therapeutic virtues. Moreover, it is particularly interesting to consider the pharmacological activities of the major phytochemical compounds present in the different extracts of this plant, such as phenolic acids, for example, coumaric and gallic acids, as well as flavonoids such as kaempferol and quercetin. Therefore, this review aims to analyze some aspects of this plant, especially the taxonomy, cytogeography, traditional uses, phytochemical constituents, and pharmacological activities of Ceratonia siliqua L., in addition to its biological properties. [ABSTRACT FROM AUTHOR]

The female reproductive tract (FRT) is home to diverse microbial communities that play a pivotal role in reproductive health and disorders such as infertility, endometriosis, and cervical cancer. To understand the complex host–microbiota interactions within the FRT, models that authentically replicate the FRT's environment, including the interplay between the microbiota, mucus layer, immune system, and hormonal cycle, are key. Recent strides in organoid and microfluidic technologies are propelling research in this domain, offering insights into FRT–microbiota interactions and potential therapeutic avenues. This review delves into the current state of FRT organoid models and microbe integration techniques, evaluating their merits and challenges for specific research objectives. Emphasis is placed on innovative approaches and applications, including integrating organoids with microfluidics, and using patient-derived biobanks, as this offers potential for deeper mechanistic insights and personalized therapeutic strategies. Modeling various FRT properties in organoids is explored, from encompassing age-related epithelial features, oxygen levels, and hormonal effects to mucus layers, immune responses, and microbial interactions, highlighting their potential to transform reproductive health research and predict possible outcomes. [ABSTRACT FROM AUTHOR]

The endometrium undergoes cyclical changes in response to hormones and there is a certain degree of heterogeneity among individuals. In vivo identification of the physiologic changes of the endometrium and the pathologic process of related diseases is challenging. There have been recent advances in the use of organoids that mimic the characteristics of the corresponding organs and the morphologic, functional, and personalized characteristics involved in different stages of diseases. In this paper, we discuss the process of creating endometrial organoids, cell sources, types of extracellular matrices, and their application in the study of physiologic endometrial states and various diseases., (© 2024 International Federation of Gynecology and Obstetrics.)

The formulation of plant extracts in phospholipid vesicles is a promising strategy to exploit their biological properties while solving problems related to poor solubility in water, high instability, and low skin permeation and retention time. In this study, Ceratonia siliqua ripe pods were used for the preparation of a hydro-ethanolic extract, which showed antioxidant properties owing to the presence of biologically active compounds identified by liquid chromatography–mass spectrometry (e.g., hydroxybenzoic acid and flavonoid derivatives). To improve the applicability of the extract in therapy, a topical formulation based on liposomes was explored. The vesicles were characterized by small size (around 100 nm), negative charge (−13 mV), and high entrapment efficiency (>90%). Furthermore, they displayed both spherical and elongated shapes, with oligolamellar structure. Their biocompatibility was demonstrated in cells, including erythrocytes and representative skin cell lines. The antioxidant activity of the extract was proved by the scavenging of free radicals, the reduction of ferric ions, and the protection of skin cells from oxidative damage. [ABSTRACT FROM AUTHOR]

Organoids are microtissues that recapitulate the complex structural organization and functions of tissues and organs. Nanoparticles have several specific properties that must be considered when replacing animal models with in vitro studies, such as the formation of a protein corona, accumulation, ability to overcome tissue barriers, and different severities of toxic effects in different cell types. An increase in the number of articles on toxicology research using organoid models is related to an increase in publications on organoids in general but is not related to toxicology-based publications. We demonstrate how the quantitative assessment of toxic changes in the structure of organoids and the state of their cell collections provide more valuable results for toxicological research and provide examples of research methods. The impact of the tested materials on organoids and their differences are also discussed. In conclusion, we highlight the main challenges, the solution of which will allow researchers to approach the replacement of in vivo research with in vitro research: biobanking and standardization of the structural characterization of organoids, and the development of effective screening imaging techniques for 3D organoid cell organization. [ABSTRACT FROM AUTHOR]

Short tandem repeats (STRs) are units of 1–6 base pairs that occur in tandem repetition to form a repeat tract. STRs exhibit repeat instability, which generates expansions or contractions of the repeat tract. Over 50 diseases, primarily affecting the central nervous system and muscles, are characterized by repeat instability. Longer repeat tracts are typically associated with earlier age of onset and increased disease severity. Environmental exposures are suspected to play a role in the pathogenesis of repeat expansion diseases. Here, we review the current knowledge of mechanisms of environmentally induced repeat instability in repeat expansion diseases. The current evidence demonstrates that environmental factors modulate repeat instability via DNA damage and induction of DNA repair pathways, with distinct mechanisms for repeat expansion and contraction. Of particular note, oxidative stress is a key mediator of environmentally induced repeat instability. The preliminary evidence suggests epigenetic modifications as potential mediators of environmentally induced repeat instability. Future research incorporating an array of environmental exposures, new human cohorts, and improved model systems, with a continued focus on cell-types, tissues, and critical windows, will aid in identifying mechanisms of environmentally induced repeat instability. Identifying environmental modulators of repeat instability and their mechanisms of action will inform preventions, therapies, and public health measures. [ABSTRACT FROM AUTHOR]

Organoids are cell cultures that are three-dimensional (3D) and include some of the most significant traits of the organ being modeled. These in vitro culture techniques can recreate some activities of the represented organ, to enable these cell types specific to organs to self-organize into a spatial arrangement comparable to that found in vivo. Adult stem cells from tissue samples, a single adult stem cell, or pluripotent stem cells that have undergone directed differentiation can all be used to create organoids. Since some organoid model systems have an active stem cell population, the organoids can be greatly expanded. Organoid culturing methods as of now have been generated to mimic the tissue architectures of the three principal cell lines. Although there are several techniques for cultivating cells that are unique to different tissues, Typically, Matrigel® or another acceptable extracellular matrix is used to implant the appropriate tissue-specific progenitor cells or pluripotent stem cells. The stem cell population is maintained by the cells being cultivated in cell culture environments with certain growth factors that closely resemble the in vivo signals needed. Under these circumstances, the interconnected cells multiply and self-organize into 3D organoids that can last forever and be accessed by many systems. In addition, these cultures have proven to be exceptionally stable genetically throughout passage; after 3 months in culture, whole genome sequencing of liver organoids made through clonal expansion from only one hepatic progenitor cell just one equivalent base mutation was found. In vitro cell culture is being revolutionized by organoids, which offer useful and medically accurate models that accurately reproduce the essential features of the modelled tissue. [ABSTRACT FROM AUTHOR]

Having biological children remains an unattainable dream for most couples with reproductive failure or gonadal dysgenesis. The combination of stem cells with gene editing technology and organ-on-a-chip models provides a unique opportunity for infertile patients with impaired gametogenesis caused by congenital disorders in sex development or cancer survivors. But how will these technologies overcome human infertility? This review discusses the regenerative mechanisms, applications, and advantages of different types of stem cells for restoring gametogenesis in infertile patients, as well as major challenges that must be overcome before clinical application. The importance and limitations of in vitro generation of gametes from patient-specific human-induced pluripotent stem cells (hiPSCs) will be discussed in the context of human reproduction. The potential role of organ-on-a-chip models that can direct differentiation of hiPSC-derived primordial germ cell-like cells to gametes and other reproductive organoids is also explored. These rapidly evolving technologies provide prospects for improving fertility to individuals and couples who experience reproductive failure. [ABSTRACT FROM AUTHOR]

Carob ( Ceratonia siliqua L.) has been widely cultivated in different parts of the world, particularly in the Mediterranean region, and the tree belongs to the family Leguminosae. Several studies have indicated that carobs and their products can improve human health and help prevent different specific chronic diseases. Carob can considered as functional food due to its high content in dietary fibers, low-fat content, and high content of minerals. Its fruit is a pod containing 10%-20% seeds, and the pods consist of sugars, proteins, crude fibers, minerals, vitamins, polyphenols, vitamins, and lipids. In many countries in the Middle east, carob is mainly used to prepare as a traditional drink and some kinds of confectioneries. The powders can be utilized to prepare carob juice concentrate. The systematic review of documents from clinical trials and scientific societies dedicated to traditional medicine in China has been carried out. The goal of this review article is a survey of chemical compounds, and pharmaceutical benefits of carob, especially by considering traditional medicinal sciences. Moreover, clinical trials research promotes studies to highlight and focus on the scope of application of traditional medicinal science in the growing system of medicine., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ovarian disease constitutes various types of endocrine disorders, such as polycystic ovarian syndrome (PCOS), ovarian cancer, premature ovarian failure, ovarian endometriosis, and ovarian cysts. The prevalence of ovarian-related diseases is highly vulnerable in the world. The utility of various drug delivery systems for ovarian diseases has resulted in varied success. Moreover, most of them lead to severe adverse effects and are incapable of ameliorating the signs and symptoms of the condition. Intrauterine devices (IUDs) have positioned themselves as a mechanism to deliver the drug for various ovarian-related diseases. Thereby avoiding various stability-related issues arising due to various physiological barriers of the female reproductive tract. However, the use of intrauterine devices for drug delivery to the ovaries has not been fully explored. This is attributed to the fact that they cause cysts in the ovaries and skepticism among patients and physicians. Photo-sensitive devices are an appealing approach for managing disorders affecting the ovaries. Photo-sensitive in situ forming intrauterine implants (IUIs) have several advantages, including simplicity in application, reduced invasiveness, as well as improved site-specific drug release control. Polymeric nanoparticles (PNPs) loaded with a drug may be a suitable choice to provide sustained release, alter the pharmacokinetics, and reduce the dose and dosing frequency. The current manuscript hypothesizes the utility of a PNP-loaded biodegradable photo-responsive intrauterine implantable device as an alternate novel strategy for ameliorating ovarian-related diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The COVID-19 pandemic has driven the scientific community to adopt an efficient and reliable model that could keep up with the infectious disease arms race. Coinciding with the pandemic, three dimensional (3D) human organoids technology has also gained traction in the field of infectious disease. An in vitro construct that can closely resemble the in vivo organ, organoid technology could bridge the gap between the traditional two-dimensional (2D) cell culture and animal models. By harnessing the multi-lineage characteristic of the organoid that allows for the recapitulation of the organotypic structure and functions, 3D human organoids have emerged as an essential tool in the field of infectious disease research. In this review, we will be providing a comparison between conventional systems and organoid models. We will also be highlighting how organoids played a role in modelling common infectious diseases and molecular mechanisms behind the pathogenesis of causative agents. Additionally, we present the limitations associated with the current organoid models and innovative strategies that could resolve these shortcomings. [ABSTRACT FROM AUTHOR]

Endometrioma (OMA) is the most common subtype of endometriosis, in which the endometriotic lesions are implanted in the ovary. Women with OMA are usually associated with infertility, presenting with reduced ovarian reserve, low oocyte quantity and quality, and poor fertility outcomes. However, the underlying pathological mechanisms in OMA-related infertility are still unclear. Due to the limitations and ethical issues of human studies in reproduction, animal models that recapitulate OMA characteristics and its related infertility are critical for mechanistic studies and subsequent drug development, preclinical testing, and clinical trials. This review summarized the investigations of OMA-related infertility based on previous and latest endometrioma models, providing the possible pathogenesis and potential therapeutic targets for further studies. [ABSTRACT FROM AUTHOR]

In recent years, stem cells have known as a helpful biological tool for the accurate diagnosis, treatment and recognition of diseases. Using stem cells as biomarkers have presented high potential in the early detection of many diseases. Another advancement in stem cell technology includes stem cell derived organoids model that could be a promising platform for diagnosis and modeling different diseases. Furthermore, therapeutic capabilities of stem cell therapy have increased hope in the face of different disability managements. All of these technologies are also widely used in reproductive related diseases especially in today's world that many couples encounter infertility problems. However, with the aid of numerous improvements in the treatment of infertility, over 80% of couples who dreamed of having children could now have children. Due to the fact that infertility has many negative effects on personal and social lives of young couples, many researchers have focused on the treatment of male and female reproductive system abnormalities with different types of stem cells, including embryonic stem cells, bone marrow mesenchymal stem cells (MSCs), and umbilical cord‐derived MSCs. Also, design and formation of reproductive system organoids provide a fascinating window into disease modeling, drug screening, personalized therapy, and regeneration medicine. Utilizing these techniques to study, model and treat the infertility‐related diseases has drawn attention of many scientists. This review explains different applications of stem cells in generating reproductive system organoids and stem cell‐based therapies for male and female infertility related diseases treatment. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs), which contain various functional classes of vesicles, namely exosomes, microvesicles, and apoptotic bodies, represent the major nano-shuttle to transfer bioactive molecules from donor to recipient cells to facilitate cell-to-cell communication in the follicular, oviduct, and uterine microenvironments. In addition to transferring various molecular cargos in the form of miRNAs, mRNAs, proteins, lipids, and DNA molecules, the relative proportion of those molecular cargos in the reproductive fluids can be associated with the physiological and pathological condition of the host animal. Inside the follicle, EV-mediated circulation of miRNAs has been reported to be associated with the growth status of the enclosed oocytes, the metabolic status, and the advanced maternal aging of the animal. Importantly, EVs have the potential to protect their cargo molecules from extracellular degradation or modification while travelling to the recipient cells. This fact together with the enormous availability in almost all biological fluids and spent culture media make them attractive in the search for biomarkers of oocyte/embryo developmental competence, receptive maternal environment and a multitude of reproductive pathophysiological conditions. One of the key factors that have contributed to the lower efficiency of assisted reproductive technologies (ART) is the absence of several maternal in vivo factors in the ART procedures. For this, several studies have been conducted to supplement various components present in the follicular and oviductal fluids into the existing ART procedures and significant positive impacts have been observed in terms of embryo cleavage rate, blastocyst rate, resistance to stress, and survival after cryopreservation. The potential of EVs in shuttling protective messages against environmental and physiological stressors has been evidenced. The effective use of the EV-coupled molecular signals against stress-associated conditions has the potential to pave the path for the application of these protective signals against oxidative stress-associated pathological conditions including PCOS, ageing, and endometritis. In this review, we provide current knowledge and potential future use of EVs as remedies in reproductive pathophysiological conditions, mainly in follicular and oviductal microenvironments. [ABSTRACT FROM AUTHOR]

The current issue (volume 13 issue 6, 2021) is a Special Issue jointly dedicated to scientific content presented at the 20th triennial IUPAB Congress that was held in conjunction with both the 45th Annual Meeting of the Brazilian Biophysical Society (Sociedade Brasileira de Biofísica - SBBf) and the 50th Annual Meeting of the Brazilian Society for Biochemistry and Molecular Biology (Sociedade Brasileira de Bioquímica e Biologia Molecular – SBBq). In addition to describing the scientific and nonscientific content arising from the meeting this sub-editorial also provides a look back at some of the high points for Biophysical Reviews in the year 2021 before going on to describe a number of matters of interest to readers of the journal in relation to the coming year of 2022. [ABSTRACT FROM AUTHOR]

Organoids hold great promises for numerous applications in biomedicine and biotechnology. Despite its potential in science, organoid technology poses complex ethical challenges that may hinder any future benefits for patients and society. This study aims to analyze the multifaceted ethical issues raised by organoids and recommend measures that must be taken at various levels to ensure the ethical use and application of this technology. Organoid technology raises several serious ethics issues related to the source of stem cells for organoid creation, informed consent and privacy of cell donors, the moral and legal status of organoids, the potential acquisition of human "characteristics or qualities", use of gene editing, creation of chimeras, organoid transplantation, commercialization and patentability, issues of equity in the resulting treatments, potential misuse and dual use issues and long-term storage in biobanks. Existing guidelines and regulatory frameworks that are applicable to organoids are also discussed. It is concluded that despite the serious ethical challenges posed by organoid use and biobanking, we have a moral obligation to support organoid research and ensure that we do not lose any of the potential benefits that organoids offer. In this direction, a four-step approach is recommended, which includes existing regulations and guidelines, special regulatory provisions that may be needed, public engagement and continuous monitoring of the rapid advancements in the field. This approach may help maximize the biomedical and social benefits of organoid technology and contribute to future governance models in organoid technology. [ABSTRACT FROM AUTHOR]

Infertility is a common problem in modern societies with significant socio-psychological implications for women. Therapeutic interventions are often needed which, depending on the cause, can either be medical treatment, surgical procedures or assisted reproductive technology (ART). However, the treatment of infertility is not always successful due to our limited understanding of the preparation of the lining of the uterus, the endometrium, for pregnancy. The endometrium is of central importance for successful reproduction as it is the site of placental implantation providing the interface between the mother and her baby. Due to the dynamic, structural and functional changes the endometrium undergoes throughout the menstrual cycle, it is challenging to study. A major advancement is the establishment of 3D organoid models of the human endometrium to study this dynamic tissue in health and disease. In this review, we describe the changes that the human endometrium undergoes through the different phases of the menstrual cycle in preparation for pregnancy. We discuss defects in the processes of endometrial repair, decidualization and acquisition of receptivity that are associated with infertility. Organoids could be utilized to investigate the underlying cellular and molecular mechanisms occurring in non-pregnant endometrium and early pregnancy. These studies may lead to therapeutic applications that could transform the treatment of reproductive failure. [ABSTRACT FROM AUTHOR]

The article discusses a 2022 study on the use of cultured trophoblast organoids from placental villi to screen the placental toxicity of 46 organophosphate flame retardants (OPFR). Results show that three of the chemicals affected cell proliferation without impairing cell survival, with 2-ethylhexyl diphenyl phosphate (EHDPP) being detected in environmental and human samples and being linked to pregnancy complications. Also noted are possible studies on functions specific to placental cells.

Adenomyosis is related to infertility and miscarriages, but so far there are no robust in vitro models that reproduce its pathological features to study the molecular mechanisms involved in this disease. Endometrial organoids are in vitro 3D models that recapitulate the native microenvironment and reproduce tissue characteristics that would allow the study of adenomyosis pathogenesis and related infertility disorders. In our study, human endometrial biopsies from adenomyosis (n = 6) and healthy women (n = 6) were recruited. Organoids were established and hormonally differentiated to recapitulate midsecretory and gestational endometrial phases. Physiological and pathological characteristics were evaluated by immunohistochemistry, immunofluorescence, qRT-PCR, and ELISA. Secretory and gestational organoids recapitulated in vivo glandular epithelial phenotype (pan-cytokeratin, Muc-1, PAS, Laminin, and Ki67) and secretory and gestational features (α-tubulin, SOX9, SPP1, PAEP, LIF, and 17βHSD2 expression and SPP1 secretion). Adenomyosis organoids showed higher expression of TGF-β2 and SMAD3 and increased gene expression of SPP1, PAEP, LIF, and 17βHSD2 compared with control organoids. Our results demonstrate that organoids derived from endometria of adenomyosis patients and differentiated to secretory and gestational phases recapitulate native endometrial-tissue-specific features and disease-specific traits. Adenomyosis-derived organoids are a promising in vitro preclinical model to study impaired implantation and pregnancy disorders in adenomyosis and enable personalized drug screening. [ABSTRACT FROM AUTHOR]

Organoids are three-dimensional (3D) multicellular tissue models that mimic their corresponding in vivo tissue. Successful efforts have derived organoids from primary tissues such as intestine, liver, and pancreas. For human uterine endometrium, the recent generation of 3D structures from primary endometrial cells is inspiring new studies of this important tissue using precise preclinical models. To improve on these 3D models, we decellularized pig endometrium containing tissue-specific extracellular matrix and generated a hydrogel (EndoECM). Next, we derived three lines of human endometrial organoids and cultured them in optimal and suboptimal culture expansion media with or without EndoECM (0.01 mg/mL) as a soluble additive. We characterized the resultant organoids to verify their epithelial origin, long-term chromosomal stability, and stemness properties. Lastly, we determined their proliferation potential under different culture conditions using proliferation rates and immunohistochemical methods. Our results demonstrate the importance of a bioactive environment for the maintenance and proliferation of human endometrial organoids. [ABSTRACT FROM AUTHOR]

Tissue chips (TCs) and microphysiological systems (MPSs) that incorporate human cells are novel platforms to model disease and screen drugs and provide an alternative to traditional animal studies. This review highlights the basic definitions of TCs and MPSs, examines four major organs/tissues, identifies critical parameters for organization and function (tissue organization, blood flow, and physical stresses), reviews current microfluidic approaches to recreate tissues, and discusses current shortcomings and future directions for the development and application of these technologies. The organs emphasized are those involved in the metabolism or excretion of drugs (hepatic and renal systems) and organs sensitive to drug toxicity (cardiovascular system). This article examines the microfluidic/microfabrication approaches for each organ individually and identifies specific examples of TCs. This review will provide an excellent starting point for understanding, designing, and constructing novel TCs for possible integration within MPS. [ABSTRACT FROM AUTHOR]