Dysregulated miRNAs in recurrent miscarriage: A systematic review.

Recurrent miscarriage (RM) is a complex reproductive medicine disease that affects many families. The cause of RM is unclear at this time; however, lifestyle and genetic variables may influence the process. The slight alteration in miRNA expression has enormous consequences for a variety of difficulties, one of which may be RM. The target of this systematic study was to provide a framework of the dysregulated miRNAs in RM. The Prisma guidelines were applied to perform current systematic review pertaining to articles in the seven databases. Thirty-nine papers out of 245 received fulfilled all inclusion requirements. From all the mentioned miRNAs, 40 were up-regulated (65.57 %), whereas 21 were down-regulated (34.43 %). These dysregulated miRNAs contributed to the pathophysiology of RM by influencing key pathways and processes such as apoptosis, angiogenesis, epithelial-mesenchymal transition, and the immune system. Understanding the dysregulation of miRNAs, as well as the pathways and processes that engage these miRNAs and impact disease pathogenesis, may aid in clarifying the unknown underlying mechanisms of RM and the development of novel molecular therapeutic targets and medical domains.

Estradiol modulated differentiation and dynamic growth of CD90+ spermatogonial stem cells toward Sertoli-like cells.

Mouse CD90+ SSCs were enriched using the MACS technique and incubated with different doses of estradiol, ranging from 0.01 ng/mL to 500 µg/mL, for 7 days. The viability of SSCs was determined using an MTT assay. The combined effects of estradiol plus Sertoli cell differentiation medium on the orientation of SSCs toward Sertoli-like cells were also assessed. Using immunofluorescence imaging, we monitored protein levels of Oct3/4 after being exposed to estradiol. In addition, protein levels of testosterone, TF, and ABP were measured using ELISA. The expression of Sertoli cell-specific genes such as SOX9, GATA4, FSHR, TF, and ESR-1 and -2 was monitored using real-time PCR assay, and the effects of 14-day injection of estradiol on sperm parameters and Oct3/4 positive progenitor cells in a model of mouse were determined. Data showed that estradiol increased the viability of mouse SSCs in a dose-dependent manner compared to the control (p < 0.05). Along with these changes, cells displayed morphological changes and reduced Oct3/4 transcription factor levels compared to the control SSCs. 7-day incubation of SSCs with estradiol led to the up-regulation of SOX9, GATA4, FSHR, TF, and ESR-1 and -2, and levels of testosterone, TF, and ABP were increased compared to the control group (p < 0.05). The in-vivo examination noted that estradiol reduced sperm parameters coincided with morphological abnormalities (p < 0.05). Histological examination revealed pathological changes in seminiferous tubules and reduction of testicular Oct3/4+ progenitor cells. In conclusion, estradiol treatment probably can induce Sertoli cell differentiation of SSCs while exogenous administration leads to testicular progenitor cell depletion and infertility in long term.

Menstrual blood CD146+ mesenchymal stem cells reduced fibrosis rate in the rat model of premature ovarian failure.

Here, the regenerative potential of menstrual blood-derived mesenchymal stem cells (MenSCs) was examined on restoration of premature ovarian failure (POF) ovaries in rats' POF model. Freshly isolated CD146+ MenSCs using magnetic-activated cell storing method were immediately injected into ovaries of POF rats. Four and eight weeks after cell administration, both ovarian tissues were sampled for histological examination and the expression of fibrosis-related genes. Serum samples were also prepared for hormonal analysis. At the endpoint, mating trials were performed to assess the fertility of POF rats following MenSC transplantation. Histopathological examination revealed the induction of POF after Ceftriaxone injection by increasing atretic follicles and abnormal morphologies. MenSCs transplantation increased the number of normal follicles and coincided with the reduction of follicular atresia. Biochemical analyses exhibited the reduction and increase of systemic follicle-stimulating hormone (FSH) and E2 respectively after MenSCs transplantation compared to the POF rats (P < .05). No significant differences in anti-mullerian hormone (AMH) blood levels were detected in this study between POF controls and MenSCs-treated rats. We noted moreover the transcriptional up-regulation of Smad 2, 4, and TGF-ß1 in POF rats, and these values were decreased after MenSCs transplantation (P < .01). By contrast, the RNA expression of Smad 6 remained increased in both pre- and post-treatment with MenSCs groups (P < .05). Finally, we found an increase in neonate births in POF rats treated with MenSCs, and that this feature was associated with ovarian rejuvenation through amelioration of fibrosis. These data showed that MenSCs are promising cell lineage for the alleviation of POF in the rat model by controlling the fibrosis rate.

Intra-ovarian injection of platelet-rich plasma into ovarian tissue promoted rejuvenation in the rat model of premature ovarian insufficiency and restored ovulation rate via angiogenesis modulation.

Premature Ovarian Insufficiency (POI) is viewed as a type of infertility in which the menopausal status occurs before the physiological age. Several therapeutic strategies have been introduced in clinic for POI treatment, although the outputs are not fully convincing. Platelet-rich plasma (PRP) is a unique blood product widely applied in regenerative medicine, which is based on the releasing of the growth factors present in platelets α-granules. In the current investigation, we examined the effectiveness of PRP as a therapeutic alternative for POI animals. POI in Wistar albino rats was induced by daily intraperitoneal (IP) administration of gonadotoxic chemical agent, 4-vinylcyclohexene dioxide (VCD) (160 mg/ kg) for 15 consecutive days. After POI induction, the PRP solution was directly injected intra-ovarian in two concentrations via a surgical intervention. Every two weeks post-injection, pathological changes were monitored in the ovaries using Hematoxylin-Eosin staining method, until eight weeks. Follicle Stimulating Hormone (FSH) content in serum was measured, together with the expression of the angiogenic-related transcripts ANGPT2 and KDR by real-time qPCR. Furthermore the fertility status of the treated rats was evaluated by mating trials. Histopathological examination revealed successful POI induction via the depletion of morphologically normal follicles in rats following VCD treatment compared to the control rats. The injection of PRP at two concentrations reduced the number and extent of the follicular atresia and inflammatory responses (p < 0.05). The expression of both ANGPT2 and KDR transcripts were significantly increased in POI rats due to enhanced inflammation, while these values were modulated after PRP administration (p < 0.05) compared to POI rats. FSH showed a decreased trend in concentration eight weeks after PRP treatment, but not statistically significant (p > 0.05). Nevertheless, a clear improvement in litter counts was found in POI rats receiving PRP compared to the non-treated POI group, being able to consider PRP as a facile, quick, accessible, safe and relatively cheap alternative therapeutic strategy to revert POI-related pathologies.

Effectiveness of Stem Cell Therapy in the Treatment of Ovarian Disorders and Female Infertility: A Systematic Review.

BACKGROUND: Infertility is a major problem worldwide. Various strategies are being used to develop better treatments for infertility and The most trending strategy is the stem cell therapy. In this study, the literature on stem cell therapy for ovarian disorders is summarized with analysis of current developments. OBJECTIVE: Different published studies on stem cell-based therapy for the treatment of various types of ovarian insufficiency and disorders such as Premature Ovarian Insufficiency (POI) in the affected female population in animal or human clinical studies are systematically reviewed. METHODS: We monitored five databases, including PubMed, Cochrane, Embase, Scopus, and ProQuest. A comprehensive online search was done using the criteria targeting the application of stem cells in animal models for menopause. Two independent reviewers carefully evaluated titles and abstracts of studies. The stem cell type, source, dosage, route of administration were highlighted in various POI animals models. Non-relevant and review articles were excluded. OUTCOMES: 648 published studies were identified during the initial comprehensive search process from which 41 were selected according to designed criteria. Based on our analysis, stem cells could accelerate ovarian tissues rejuvenation, regulate systemic sex-related hormones levels and eventually increase fertility rate. CONCLUSION: The evidence suggests that stem cell-based therapies could be considered as an alternative modality to deal with women undergoing POI.

Ovarian function and reproductive outcome after ovarian tissue transplantation: a systematic review.

The aim of this systematic review study is to summarize the current knowledge of ovarian tissue transplantation and provide insight on ovarian function, fertility and reproductive outcome following ovarian tissue transplantation. Relevant studies were identified by searching through PubMed, Cochrane Library, Embase, ProQuest, and Scopus databases until August 2018. Ovarian function by examination of the hormonal level was evaluated, together with follicular growth, the return of menstrual cycle and assessment of reproductive consequences: pregnancy, miscarriage rates and live birth after transplantation. Studies including female patients aged between 22 and 49 years that were subjected to ovarian tissue transplantation were considered. A total of 1185 studies were identified in the primary search. Titles and abstracts were screened for assessment of the inclusion criteria. Finally, twenty-five articles met the criteria and were included in this study. In general, 70% of patients that underwent ovarian tissue transplantation had ovarian and endocrine function restoration as well as follicular growth. Pregnancy was reported with 52% of the patients. The available evidence suggests that ovarian tissue transplantation is a useful and an applied approach to restore hormonal function, endocrine balance and eventually fertility outcomes in patients that are predisposed to lose their fertility, diagnosed with premature ovarian failure (POF), as well as women undergoing cancer treatments. Identification of the techniques with the lowest invasions for follicular and oocyte development after ovarian tissue transplantation aiming to reduce probable adverse effects after treatment is indispensable.