Premature ovarian insufficiency (POI) is a condition characterized by amenorrhea, hypergonadotropic hypogonadism, estrogen deficiency, and reduced follicle counts leading to infertility under the age of 40. POI occurs in approximately 1-3% of women in the general population. Evaluation is warranted when the diagnosis of POI is made to rule out underlying etiologies, which could be multifactorial. This review serves to cover the novel treatment approaches reported in the literature.
Background Primary ovarian insufficiency (POI) refers to the loss of ovarian function under the age of 40 and results in amenorrhea and infertility. Our previous studies have shown that transplantation of mesenchymal stem cells (MSCs) and MSC-derived exosomes in chemotherapy-induced POI mouse ovaries can reverse the POI and eventually achieve pregnancy. Based on our recent studies, MSC-derived exosomes have almost equal therapeutic potentials as transplanted MSCs. However, it is still unclear whether exosomes can completely replace MSCs in POI treatment. For the reliable application of cell-free treatment for POI patients using exosomes, there is a need to understand whether there is any outcome and effectiveness difference between MSC and MSC-derived exosome treatment. Methods Comparing the therapeutic effect of intravenous injection using MSCs and equal amounts of exosomes in a POI mouse model will reveal the difference between the two therapeutic resources. In this study, we induced POI in C57/BL6 mice by chemotherapy (CXT) using a standard protocol. We then injected four different doses of MSCs or equal amounts of commercialized MSC-derived exosomes by retro-orbital injection post-CXT. Result After MSC/exosome treatment, tissue and serum samples were harvested to analyze molecular changes after treatment, while other mice in parallel experiments underwent breeding experiments to compare the restoration of fertility. Both the MSC- and exosome-treated groups had a restored estrous cycle and serum hormone levels compared to untreated POI mice. The pregnancy rate in the MSC-treated group was 60–100% after treatment, while the pregnancy rate in the exosome-treated group was 30–50% after treatment. Interestingly, in terms of long-term effects, MSC-treated mice still showed a 60–80% pregnancy rate in the second round of breeding, while the exosome-treated group became infertile again in the second round of breeding. Conclusions Although there were some differences in the efficacy between MSC treatment and exosome treatment, both treatments were able to achieve pregnancy in the POI mouse model. In conclusion, we report that MSC-derived exosomes are a promising therapeutic option to restore ovarian function in POI conditions similar to treatment with MSCs.
Objective: To determine the development and the localization of the ovaries during the fetal period. Material and Methods: One hundred and fifty-four ovaries obtained from 77 human fetuses aged between 9 and 40 weeks of gestation were used in this study. Firstly, the shapes and the positions of the ovaries were established. Second, the localization of the ovaries with respect to linea terminalis, ureters, and the iliac arteries were determined. Finally, the dimensions and the weight of the ovaries were measured. Findings: In the fetal period, the ovaries were most commonly almond shaped and had an oblique orientation. In the 1st trimester the midpoint of the long axis of the fetal ovaries were at the level of linea terminalis. In the 2nd and 3rd trimester and full-term fetuses, it was observed that the ovaries were not in ovarian fossa, suggesting that descensus ovary was in progression during these times. During the intrauterine period, the ovaries were most commonly located anterior to the ureters and over the common iliac artery, only to migrate to its final location between the internal and external iliac arteries towards the end of the 40th week. Conclusion: We found that the ovaries did not assume the position of the adults at the end of the fetal period, rather continued its descent after the birth. We believe our findings about the fetal ovaries will be useful in obstetrics, fetal pathology, and forensic pathology.
The objective of this study was to explore the fetal development of the stomach, its morphology and relationship with neighboring structures. The study is carried out in 2003 using 160 human embryos and fetuses (81 males and 79 females) aged between 9 and 40 weeks of gestation. None of the cases had any external pathology or anomaly. Its topographical localization and relationship with surrounding structures were revealed with anatomical dissections. Width and height of the stomach, lengths of the greater and lesser curvatures, the angle between horizontal and vertical axes of the stomach and types of stomach were established. During the fetal life stomach was most commonly located above the transverse axis passing through the umbilicus, in left and right hypochondrium (81%). There were significant differences among trimester groups with respect to the localization of the stomach in the quadrants (P < 0.001). There were no significant sex differences in parameters. After the second trimester, the height of the stomach increased more than the width of the stomach and anterior abdominal height. The angle of stomach decreased from 100 degrees to 50 degrees throughout the fetal period. During the fetal period, wide angles stomach was more common in the first(f) and second trimesters while acute-angled stomach was more common in the third trimester and term fetuses. Diagnosis and treatment of fetal anomalies and pathologies of the stomach requires knowledge of fetal anatomy of the stomach. Data acquired in this study are believed to contribute to the studies of obstetrics, perinatology, forensic medicine and fetal pathology on fetal development of the stomach, and diagnosis and treatment of its anomalies, pathologies, and variations.
Polycystic ovary syndrome (PCOS) is known as the most common endocrine disorder in women. Previously, we suggested that human mesenchymal stem cells (MSCs) can reverse the PCOS condition by secreting factors. Here, we evaluated the therapeutic capability of MSC-derived extracellular vesicles (EVs), also known as exosomes, in both in vitro and in vivo PCOS models. Exosomes were used to treat androgen-producing H293R cells and injected in a mouse model through intraovarian and intravenous injection into a letrozole (LTZ)-induced PCOS mouse model. We assessed the effects of the exosomes on androgen-producing cells or the PCOS mouse model by analyzing steroidogenic gene expression (quantitative real-time polymerase chain reaction (qRT–PCR)), body weight change, serum hormone levels, and fertility by pup delivery. Our data show the therapeutic effect of MSC-derived EVs for reversing PCOS conditions, including fertility issues. Interestingly, intravenous injection was more effective for serum glucose regulation, and an intraovarian injection was more effective for ovary restoration. Our study suggests that MSC-derived exosomes can be promising biopharmaceutics for treating PCOS conditions as a novel therapeutic option. Despite the fact that we need more validation in human patients, we may evaluate this novel treatment option for PCOS with the following clinical trials.
Software organizations have to develop software in a short time, and quickly respond to changing requirements. Recently, organizations have started to implement agile development models to reduce cost and increase productivity and quality. Scrum, one of the most widely used agile methodologies, is often implemented in various ways that depart in an uncontrolled fashion from the original model, resulting in development methods often called “ScrumBut.” Some argue that such incomplete implementations violate Scrum's core practices and philosophy, while others propose that all methodologies should be adapted to organization's unique culture and integrated with their best practices. In this research, a Blended Scrum model was proposed to overcome uncontrolled ScrumBut issues while transitioning to Scrum. The study was organized as a case study in which software professionals working in Scrum teams were interviewed. In addition, a questionnaire was conducted with other software professionals to determine how agile methods, specifically Scrum, were used. The interviews and questionnaire revealed various Scrum practical implementations. The Blended Scrum model was developed by integrating original Scrum with practices that were determined by interviews and questionnaire conducted with software professionals with real‐world Scrum experience. Finally, the Blended Scrum model was evaluated by Scrum professionals and received positive feedback.
Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in reproductive-aged women, and it typically involves elevated androgen levels. Recently, it has been reported that human bone marrow mesenchymal stem cells (hBM-MSCs) can regulate androgen synthesis pathways. However, the details of the mechanism are still unclear. hBM-MSC-derived secreted factors (the secretome) are promising sources of cell-based therapy as they consist of various types of proteins. It is thus important to know which proteins interact with disease-implicated biomolecules. This work aimed to investigate which secretome components contain the key factor that inhibits testosterone synthesis. In this study, we fractionated hBM-MSC-conditioned media into three fractions based on their molecular weights and found that, of the three fractions, one had the ability to inhibit the androgen-producing genes efficiently. We also analyzed the components of this fraction and established a protein profile of the hBM-MSC secretome, which was shown to inhibit androgen synthesis. Our study describes a set of protein components present in the hBM-MSC secretome that can be used therapeutically to treat PCOS by regulating androgen production for the first time.
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