Chemotherapy induces an irreversible premature ovarian dysfunction (POD). Amniotic fluid mesenchymal stem cells (AFMSCs) can rescue fertility; however, the notion that stem cells can rejuvenate follicles is highly controversial due tthe predetermined ovarian reserve. This study aims to isolate AFMSC-derived extracellular vesicles (EVs) and investigate their abundancy for the anti-apoptotic miRNA-21 as a means of ovarian restoration. Female rats were divided into healthy controls and POD-induced groups. The POD induced groups were subdivided into three groups according to the therapies they received: placebo-treated POD, AFMSC and EVs groups. Rats were assessed for serum anti-Müllerian hormone (AMH) levels, ovarian caspase 3 and PTEN protein levels in the ovarian lysate. Total follicular counts (TFC) were estimated from stained ovarian sections. Functional recovery was investigated through daily vaginal smears and mating trials. In-vitro chemical transfection of the AFMSCs with selective miRNA-21 mimics/inhibitors followed by isolation of EVs for therapy was conducted in two additional groups. At the interval points studied, treatment with AFMSCs and EVs equally restored TFC, AMH levels, regular estrous cycles and fruitful conception, while it both diminished caspase 3 and PTEN levels. EVs carrying miRNA-21 mimics recapitulated the short-term effects. Placebo-treated POD or EVs carrying miRNA-21 inhibitors showed augmented ovarian follicular damage demonstrated the low AMH levels, TFC and high levels of PTEN and caspase 3. miRNA-21 allowed regeneration by modulating PTEN and caspase 3 apoptotic pathways. Our findings exemplify that EVs could serve as an innovative cell-free therapeutic tool functioning through their miRNA content and that miRNA-21 has a chief regenerative role through modulating PTEN and caspase 3 apoptotic pathways.
Diabetic nephropathy (DN) is one of the most common causes of chronic kidney diseases (CKDs) that have been associated with high morbidity and mortality.Recently, several studies have highlighted the protective role of vitamin D3 (VD3) and omega-3 fatty acids (O3-FAs) in CKDs. However, their effect on DN is still unclear.Aims: This study aimed to evaluate the effects of both VD3 and / or O3-FAs in slowing the progression of DN through their impact on indices of renal function, glycemic control, oxidative stress and markers of podocyte injury. Materials and methods: type I diabetes was induced in albino rats by single intraperitoneal injection of streptozotocin (65mg/kg). Rats received daily oral administration of VD3 and O3-FAs separately and in combination for 6 weeks. Results: VD3 and O3-FAs therapy improved significantly hyperglycemia, renal function tests, with concomitant decrease in total urinary protein content, urinary nephrin, a marker of podocyte injury and renal oxidative stress. However, the combined therapy was superior in its effect over VD3 and O3-FAs separately. Such results were confirmed by renal cortical tissue assessment using light microscopic examination of H&E and PAS stains in addition to transmission-electron microscopy. Conclusions: VD3 and O3-FAs have a potential beneficial effect on amelioration of structural changes in pedicels and glomerular basement membrane that was reflected as evident renal functional restoration.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.