الفهرس 
List of Contentsيوجد فقط 14 صفحة متاحة للعرض العام
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المستخلص
Background : Cisplatin (Cis) is a widely used chemotherapy for several types of cancer. However, it causes complications in ovarian Folliculogenesis and ovulation that leads to female infertility. Therefore, the current study was carried out to estimate the therapeutic potentiality of Mesenchymal stem cells(MSCs) preconditioned with an autophagy inducer to accelerate the cells survival and migration on Cis induce ovarian toxicity. Material and methods:The study included two phases; in vitro study for autophagy induction in ADMSCs with rapamycin (Rapa). In vivo study included one hundred and twenty female Sprague-Dawley mature rats divided into 5 groups (24 in each); Control group: animals were injected intraperitoneally (i.p.) with 0.9 % saline. Cis group: animals were injected i.p. with five consecutive2.5 mg/kg Cis daily followed by a seven-day recovery and a second series of five i.p. daily injection. Rapa group: this was a Cis group with i.p. administration of 2 mg/kg rapa dissolved in DMSO after 1 week of last injection of Cis ADMSCs group: this was a Cis group with i.v. administration of 0.1 mL ADMSC cells after 1 week of last injection of Cis. ADMSCs+ Rapa group: this was a Cis group with i.v. administration of0.1mL ADMSC cells pretreated with 50nM of Rapa 2 hrs prior to administration. The sacrifice was carried out in two different intervals, 2 and 6 weeks. Half animals were sacrificed and the ovaries were harvested for biochemical, molecular and immunohistopathological studies, while the other half was kept for mating and fertility index evaluation. Result : ADMSCs treated with Rapa showed extensively augmentation of autophagic activities compared to the untreated cells (p < 0.05). After transplantation of ADMSCs pretreated with Rapa, a significant enhancement in the FSH, LH and E2 hormonal levels was detected compared to Cis group at 2 and 6 weeks (p < 0.05). Moreover, an increase in the antioxidant activity was observed after 2 and 6 weeks of treatment. Furthermore, there was a significant improvement in follicular count and quality. In addition, a significant increase in the gene and protein expression of the anti-apoptotic marker BCL-2was observed compared to Cis group and ADMSCs group (p < 0.05). Interestingly, fertility index analysis manifested a completely restoring in the reproductive capacity in ADMSCs+ Rapa group compared to Cis group and ADMSCs at the two time intervals (p < 0.05). Conclusion: Autophagy induction could enhanced the viability of ADMSCs, which in turn restored the Folliculogenesis process after exposure to Cis. Therefore, it could be used as an adjuvant therapy to save females reproductive life.