Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Rapamycin Induced Autophagy in Mesenchymal Stem Cells Modulates Cell Survival After Transplantation in a Rat Model with Cisplatin-Induced Ovarian Toxicity via Deactivation of the mTOR Pathway

Amira Sarhan
,
Ahmed A. Shokeir
* ,
Saleh A Saleh
ORCID logo ,
Heba M. Adly
,
Ikhlas A Sindi
,
Mamdouh Eldesoqui
,
Mohamed El-Sherbiny
ORCID logo ,
Amira Awadalla
,
Amoura M Aboualnaga
Version 1 : Received: 11 July 2023 / Approved: 11 July 2023 / Online: 12 July 2023 (09:36:41 CEST)

How to cite: Sarhan, A.; Shokeir, A.A.; Saleh, S.A.; Adly, H.M.; Sindi, I.A.; Eldesoqui, M.; El-Sherbiny, M.; Awadalla, A.; Aboualnaga, A.M. Rapamycin Induced Autophagy in Mesenchymal Stem Cells Modulates Cell Survival After Transplantation in a Rat Model with Cisplatin-Induced Ovarian Toxicity via Deactivation of the mTOR Pathway. Preprints 2023, 2023070798. https://doi.org/10.20944/preprints202307.0798.v1 Sarhan, A.; Shokeir, A.A.; Saleh, S.A.; Adly, H.M.; Sindi, I.A.; Eldesoqui, M.; El-Sherbiny, M.; Awadalla, A.; Aboualnaga, A.M. Rapamycin Induced Autophagy in Mesenchymal Stem Cells Modulates Cell Survival After Transplantation in a Rat Model with Cisplatin-Induced Ovarian Toxicity via Deactivation of the mTOR Pathway. Preprints 2023, 2023070798. https://doi.org/10.20944/preprints202307.0798.v1

Abstract

Purpose: We aimed to evaluate the impact of preconditioning adipose-derived mesenchymal stem cells (ADMSCs) with the autophagy inducer rapamycin (Rapa) on Cisplatin (Cis) induced ovarian toxicity in a rat model. Methods: ADMSCs were pretreated with 50 nmol/L rapa for two h in vitro. Another in vivo study included 96 female Sprague-Dawley rats divided into four equal groups: control, Cis, Cis +ADMSCs, and Cis +ADMSCs + Rapa. Rats were sacrificed after 2 and 6 weeks. Each group was subdivided into two equal subgroups: 6 rats were sacrificed to study ovarian parameters, and six were left for mating to evaluate the fertility index. Results: Autophagy activation was detected in ADMSCs + Rapa by increasing autophagosomes, high autophagy-specific LC3-II gene and protein expression, and low expression of p62 and mTOR genes. Moreover, transplantation of ADMSCs + Rapa restored balance between E2, FSH, and LH, increased antioxidant activity, and improved follicular count and quality after 2 and 6 weeks of treatment. Fertility index analysis manifested restoring reproductive capacity in the ADMSCs+ Rapa group at both intervals. Conclusions: Autophagy induction could enhance the therapeutic capability of ADMSCs by deactivating the mTOR pathway, which in turn promotes the ovarian folliculogenesis process after exposure to Cis.

Keywords

Autophagy; Cisplatin; MSCs; Ovaries; Rapamycin; Rats

Subject

Biology and Life Sciences, Cell and Developmental Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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