scholarly journals COMPARISON OF THERAPEUTIC EFFECTS OF DIFFERENT METHODS OF ADMINISTRATION OF MEZENCHIMAL STEM CELLS TO MICE WITH PREMATURE OVARIAN INSUFFICIENCY

2021 ◽  
Vol 76 (2) ◽  
pp. 35-40
Author(s):  
M. I. Kozub ◽  
K. P. Skybina ◽  
I. B. Musatova ◽  
O. V. Prokopiuk ◽  
S. M. Gramatiuk ◽  
...  

Premature ovarian insufficiency (POI) is condition of female hypogonadism. One of the reasons for the development of POI is anticancer chemotherapy. Currently, hormone replacement therapy is considered the most effective method of treatment POI, which, however, had a number of side effects, requires constant administration of pharmaceuticals, did not restore fertility and correct pathological changes in target organs. Therefore, the search for alternative methods of treatment based on the use of stem cells is promising. The aim of work was to compare the therapeutic effects of different methods of administration of mesenchymal stem cells isolated from adipose tissue (AT MSCs) in restoring sexual function, as well as the behavior of mice with chemotherapy-induced premature ovarian failure. Materials and methods. The investigation was carried out on BALB/c mice with a POI model induced by Cyclophosphamide and Busulfan. A histological examination of preparations of the ovaries and uterus was carried out. We studied the changes in the weight of mice, ovarian function, sexual activity, as well as the behavior of animals in anxiolytic and zoosocial tests after treatment with AT MSCs with intraperitoneal and intraovarian routes of administration. Results and discussion. It was shown that the effectiveness of the use of AT MSCs depends on the method of their administration at the treatment of POI induced by chemotherapy. More rapid and complete restoration of the morphological structure, sexual function, and behavioral responses were observed in mice with POI treated by intraovarial administration of AT MSCs.  

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yan Zhao ◽  
Jiao Ma ◽  
Peiye Yi ◽  
Jun Wu ◽  
Feiyan Zhao ◽  
...  

Abstract Background Premature ovarian insufficiency (POI) is an ovarian dysfunction that seriously affects a woman’s physiological health and reproduction. Mesenchymal stem cell (MSC) transplantation offers a promising treatment option for ovarian restoration in rodent POI models. However, the efficacy and mechanism of it remain unclear. Methods POI mice model was generated by cyclophosphamide and busulfan, followed with the treatment of tail-vein injection of the human umbilical cord mesenchymal stem cells (hUCMSCs). Maternal physiological changes and offspring behavior were detected. To reveal the pathogenesis and therapeutic mechanisms of POI, we first compared the metabolite profiles of healthy and POI ovarian tissues using untargeted metabolomics analyses. After stem cell therapy, we then collected the ovaries from control, POI, and hUCMSC-treated POI groups for lipid metabolomics and pseudotargeted metabolomics analysis. Results Our results revealed remarkable changes of multiple metabolites, especially lipids, in ovarian tissues after POI generation. Following the transplantation of clinical-grade hUCMSCs, POI mice exhibited significant improvements in body weight, sex hormone levels, estrous cycles, and reproductive capacity. Lipid metabolomics and pseudotargeted metabolomics analyses for the ovaries showed that the metabolite levels in the POI group, mainly lipids, glycerophospholipids, steroids, and amino acids changed significantly compared with the controls’, and most of them returned to near-healthy levels after receiving hUCMSC treatment. Meanwhile, we also observed an increase of monosaccharide levels in the ovaries from POI mice and a decrease after stem cell treatment. Conclusions hUCMSCs restore ovarian function through activating the PI3K pathway by promoting the level of free amino acids, consequently improving lipid metabolism and reducing the concentration of monosaccharides. These findings provide potential targets for the clinical diagnosis and treatment of POI.


2021 ◽  
Vol 22 (17) ◽  
pp. 9336
Author(s):  
Katarzyna Pankiewicz ◽  
Piotr Laudański ◽  
Tadeusz Issat

Premature ovarian insufficiency (POI) is defined as a loss of ovarian function before the age of 40 years, with a prevalence rate estimated at approximately 1%. It causes infertility and is related to serious long-term health consequences, including reduced life expectancy, increased cardiovascular risk, decreased bone mineral density and neurological disorders. There is currently no effective therapy for POI that is widely available in clinical practice; therefore, the treatment of patients with POI is based on hormone replacement therapy. One of the recent advances in the understanding of the pathophysiology of POI has been the role of microRNAs (miRNAs) and other noncoding RNAs (ncRNAs) in the disease. Moreover, intensive research on human folliculogenesis and reproductive biology has led to the development of novel promising therapeutic strategies with the use of exosomal miRNAs derived from mesenchymal stem cells to restore ovarian function in POI patients. This narrative review focuses on the new studies concerning the role of ncRNAs in the pathogenesis of POI, together with their potential as biomarkers of the disease and targets for therapy.


2020 ◽  
pp. 1-2
Author(s):  
Anupama Bahadur ◽  
Rajlaxmi Mundhra ◽  
Aditi Jindal ◽  
Latika Chawla ◽  
Kavita Khoiwal ◽  
...  

Introduction: Premature ovarian insufficiency (POI) is a depletion of normal ovarian function before age of 40 years accompanied by cessation of menstruation. A couple must be counseled on the effect of POI on future fertility and once diagnosed a woman needs to be evaluated annually. She requires hormone replacement therapy for bone support, cardiovascular and sexual health. Material and methods: A prospective study was conducted in department of Obstetrics and Gynecology at AIIMS Rishikesh from November 2016 to November 2018. We studied the sociodemographic profile, etiology, clinical presentation of 30 patients presenting with POI. Women less than 40 years of age with amenorrhea lasting for four months with two FSH levels in menopausal range (> 40 mIU/ml) obtained atleast one month apart were included in the study. Results: 18 (60%) women presented with amenorrhea between 1 to 2 years. 17 (56.67%) women belonged to urban region and 13 (43.33%) resided in rural area. 22 (73.3%) women had infertility of which 17 (77.27%) had primary infertility and 5 (22.72%) had secondary infertility. For the rest 8 (26.66%) women hypoestrogenic symptom, including vasomotor was the major concern. Conclusion: When POI is diagnosed in adolescent females, patient and her family are often unprepared for such news and its implications are compromised fertility and impaired self-esteem as well as long term hormonal therapy. As clinician we should be mindful of the sensitive nature of this medical condition.


Author(s):  
Spiridenko G.Yu. ◽  
Petrov Yu.A. ◽  
Palieva N.V.

Infertility is currently a priority problem for women of reproductive age. One of the reasons for this condition may be premature ovarian insufficiency. This is a pathological process causes by primary hypogonadism that occurs in women under 40 years of age. Its prevalence varies from 1:10,000 at the age of 20 to 1:100 at an older age. The absence of specific clinical manifestations of the disease complicates its early diagnosis and timely treatment. This pathological process manifests itself as secondary oligo-or amenorrhea, infertility. Less often, before the onset of reproductive disorders, there are manifestations of estrogenic insufficiency - vasomotor disorders - hot flashes, hyperhidrosis, cephalgia, tachycardia, arterial hypertension, emotional and vegetative disorders-irritability, asthenic manifestations, anxiety, depression, hypo - thymia, decreased libido. The lack of accurate data on etiological factors makes it harder to find methods for preventing this disease. The main direction of treatment is hormone replacement therapy, aimed at eliminating the insufficiency of natural estrogens in the woman's body. The chances of successful realization of the reproductive potential depend on the value of the follicle-stimulating hormone, since its high concentration affects the mitotic activity of granulosa cells of the follicle, which confirms the validity of hormone replacement therapy. The non-occurrence of pregnancy after therapy forces the patient to use assisted reproductive technologies using donor embryos and oocytes, while the effectiveness of in vitro fertilization does not exceed 58%. To prevent this outcome, if a woman has risk factors for developing premature ovarian insufficiency, it is necessary to timely assess the ovarian reserve with the preservation of her own oocytes for subsequent assisted reproductive technologies.


2019 ◽  
Vol 26 (12) ◽  
pp. 1633-1639 ◽  
Author(s):  
Andres Reig ◽  
Ramanaiah Mamillapalli ◽  
Alexis Coolidge ◽  
Joshua Johnson ◽  
Hugh S. Taylor

Primary ovarian insufficiency (POI) is defined as ovarian dysfunction in women younger than 40 years. It affects 1% of the women in this age-group and can occur iatrogenically after chemotherapy. Stem cells have been used in attempt to restore ovarian function in POI. In particular, endometrial mesenchymal stem cells (eMSCs) are easily obtainable in humans and have shown great potential for regenerative medicine. Here, we studied the potential for uterine cell (UC) suspensions containing eMSCs to improve ovarian function in a murine model of chemotherapy-induced POI. Green fluorescent protein (GFP)-labeled UC or phosphate-buffered solution (PBS) was delivered intravenously after chemotherapy. There was a significant increase in oocytes production and serum anti-Müllerian hormone concentrations after 6 weeks, as well as a 19% higher body mass in UC-treated mice. Similarly, we observed an increased number of pups in mice treated with UC than in mice treated with PBS. None of the oocytes or pups incorporated GFP, suggesting that there was no contribution of these stem cells to the oocyte pool. We conclude that treatment with UC indirectly improved ovarian function in mice with chemotherapy-induced POI. Furthermore, our study suggests that endometrial stem cell therapy may be beneficial to young women who undergo ovotoxic chemotherapy.


2016 ◽  
Vol 86 (2) ◽  
pp. 223-228 ◽  
Author(s):  
Anne Bachelot ◽  
Carole Nicolas ◽  
Maud Bidet ◽  
Jérôme Dulon ◽  
Monique Leban ◽  
...  

2021 ◽  
Vol 5 (2) ◽  
pp. 49-56
Author(s):  
K P Vidya ◽  
Divya U ◽  
Sithara Satheesan

Premature ovarian insufficiency (POI) is defined as a cessation of ovarian function before the age of 40 years. It is associated with hypoestrogenism and loss of residual follicles, both of which lead to menstrual abnormalities, pregnancy failures, and decreased health-related quality of life. The prevalence of POI is estimated at 1% in the general population. The risk of premature ovarian insufficiency (POI) before the age of 40 years is 1 %. The aetiopathology of premature ovarian insufficiency in the majority of cases is unknown and is termed as spontaneous or idiopathic POI. This is a case with signs and symptoms of POI which was developed after the administration of GnRH agonist drugs as a part of treatment of endometriosis. In this single case study, a female of 33 years having complaints of absence of periods since 6 months treated with Ayurveda treatment with pre and post evaluation. The symptoms of secondary amenorrhoea, hot flashes, vaginal dryness and mood swings were relieved after Ayurveda medications and procedures.


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