Optimized platelet rich plasma releasate (O-rPRP) repairs galactosemia-induced ovarian follicular loss in rats by activating mTOR signaling and inhibiting apoptosis

Bakly, Wesam El; Medhat, Marwa; Shafei, Mohamed; Tash, Reham; Elrefai, Mohamed Fathi Mohamed; Shoukry, Yousef; Omar, Nesreen Nabil

doi:10.1016/j.heliyon.2020.e05006

Cited by 6 publications

(4 citation statements)

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“…Cyclophosphamide and cisplatin are commonly used in clinical practice, and becoming the most common method of establishing an animal model of POI. In addition, other recognized causes of POI include metabolism disorders, infections, toxins, and environmental factors ( Naleway et al, 2018 ; Moslehi et al, 2019 ; Rostami Dovom et al, 2019 ; El Bakly et al, 2020 ).…”

Section: The Pathogenesis Of Poi and The Application Of Stem Cell-der...mentioning

confidence: 99%

Stem cell-derived extracellular vesicles: A novel and potential remedy for primary ovarian insufficiency

Geng

Guo²,

Li³

et al. 2023

Front. Cell Dev. Biol.

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Primary ovarian insufficiency (POI) is an essential cause of young female fertility loss. At present, there are many treatments for primary ovarian insufficiency, but due to the complexity of the pathogenesis of primary ovarian insufficiency, the efficacy still could not be satisfactory. Stem cell transplantation is a feasible intervention protocol for primary ovarian insufficiency. However, its wide application in the clinic is limited by some defects such as tumorigenic and controversial ethical issues. Stem cell-derived extracellular vesicles (EVs) represent an important mode of intercellular communication attracting increasing interest. It is well documented that stem cell-derived extracellular vesicles for primary ovarian insufficiency with exciting therapeutic effects. Studies have found that stem cell-derived extracellular vesicles could improve ovarian reserve, increase the growth of follicles, reduce follicle atresia, and restore hormone levels of FSH and E2. Its mechanisms include inhibiting ovarian granulosa cells (GCs) apoptosis, reactive oxygen species, and inflammatory response and promoting granulosa cells proliferation and angiogenesis. Thus, stem cell-derived extracellular vesicles are a promising and potential method for primary ovarian insufficiency patients. However, stem cell-derived extracellular vesicles are still a long way from clinical translation. This review will provide an overview of the role and the mechanisms of stem cell-derived extracellular vesicles in primary ovarian insufficiency, and further elaborate on the current challenges. It may suggest new directions for future research.

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Section: The Pathogenesis Of Poi and The Application Of Stem Cell-der...mentioning

confidence: 99%

Stem cell-derived extracellular vesicles: A novel and potential remedy for primary ovarian insufficiency

Geng

Guo²,

Li³

et al. 2023

Front. Cell Dev. Biol.

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“…Moreover, Balakrishnan et al (2016) showed that GalT KO fibroblasts had downregulated PI3K/AKT signaling and decreases in the IGF-1 receptor. Lastly, it has been proposed that galactose-induced stress activates the expression of the micro-RNA miR-223 ( El Bakly et al , 2020 ), which could then impede cell proliferation, partly by targeting the IGF-1 receptor and inhibiting its downstream PI3K/AKT pathway ( Jia et al , 2011 ; Pan et al , 2014 ).…”

Section: Onset and Mechanism Of Damage Including Potential Signaling ...mentioning

confidence: 99%

The hypergonadotropic hypogonadism conundrum of classic galactosemia

Derks

Rivera-Cruz

Hagen-Lillevik

et al. 2022

Human Reproduction Update

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BACKGROUND Hypergonadotropic hypogonadism is a burdensome complication of classic galactosemia (CG), an inborn error of galactose metabolism that invariably affects female patients. Since its recognition in 1979, data have become available regarding the clinical spectrum, and the impact on fertility. Many women have been counseled for infertility and the majority never try to conceive, yet spontaneous pregnancies can occur. Onset and mechanism of damage have not been elucidated, yet new insights at the molecular level are becoming available that might greatly benefit our understanding. Fertility preservation options have expanded, and treatments to mitigate this complication either by directly rescuing the metabolic defect or by influencing the cascade of events are being explored. OBJECTIVE AND RATIONALE The aims are to review: the clinical picture and the need to revisit the counseling paradigm; insights into the onset and mechanism of damage at the molecular level; and current treatments to mitigate ovarian damage. SEARCH METHODS In addition to the work on this topic by the authors, the PubMed database has been used to search for peer-reviewed articles and reviews using the following terms: ‘classic galactosemia’, ‘gonadal damage’, ‘primary ovarian insufficiency’, ‘fertility’, ‘animal models’ and ‘fertility preservation’ in combination with other keywords related to the subject area. All relevant publications until August 2022 have been critically evaluated and reviewed. OUTCOMES A diagnosis of premature ovarian insufficiency (POI) results in a significant psychological burden with a high incidence of depression and anxiety that urges adequate counseling at an early stage, appropriate treatment and timely discussion of fertility preservation options. The cause of POI in CG is unknown, but evidence exists of dysregulation in pathways crucial for folliculogenesis such as phosphatidylinositol 3-kinase/protein kinase B, inositol pathway, mitogen-activated protein kinase, insulin-like growth factor-1 and transforming growth factor-beta signaling. Recent findings from the GalT gene-trapped (GalTKO) mouse model suggest that early molecular changes in 1-month-old ovaries elicit an accelerated growth activation and burnout of primordial follicles, resembling the progressive ovarian failure seen in patients. Although data on safety and efficacy outcomes are still limited, ovarian tissue cryopreservation can be a fertility preservation option. Treatments to overcome the genetic defect, for example nucleic acid therapy such as mRNA or gene therapy, or that influence the cascade of events are being explored at the (pre-)clinical level. WIDER IMPLICATIONS Elucidation of the molecular pathways underlying POI of any origin can greatly advance our insight into the pathogenesis and open new treatment avenues. Alterations in these molecular pathways might serve as markers of disease progression and efficiency of new treatment options.

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“…Currently, mRNA therapies are being investigated at the preclinical stage for the disease and might be promising treatment options to store defective proteins 87,[89][90][91] . Rescuing GALT activity with pharmacological chaperones has also been proposed as a potential therapeutic option 92 .…”

Section: Part Iii: Exploring New Treatment Options For Cgmentioning

confidence: 99%

“…receptor. Lastly, it has been proposed that galactose-induced stress activates the expression of the micro-RNA miR-223 89 , which could then impede cell proliferation, partly by targeting the IGF-1 receptor and inhibiting its downstream PI3K/AKT pathway 71,73 .…”

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Galactosemias

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Optimized platelet rich plasma releasate (O-rPRP) repairs galactosemia-induced ovarian follicular loss in rats by activating mTOR signaling and inhibiting apoptosis

Cited by 6 publications

References 74 publications

Stem cell-derived extracellular vesicles: A novel and potential remedy for primary ovarian insufficiency

Stem cell-derived extracellular vesicles: A novel and potential remedy for primary ovarian insufficiency

The hypergonadotropic hypogonadism conundrum of classic galactosemia

Galactosemias

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