{"doi":"10.20944/preprints202307.0798.v1","title":"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","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.","journal":"Preprints.org","year":2023,"id":400074,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9444,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1176362,"name":"Ahmed A. Shokeir","orcid":"0000-0001-6386-3215","position":1,"is_corresponding":false},{"id":1176363,"name":"Saleh A. K. Saleh","orcid":"0000-0001-9522-9198","position":2,"is_corresponding":false},{"id":1176364,"name":"Heba M. Adly","orcid":"0000-0002-9222-9149","position":3,"is_corresponding":false},{"id":1176365,"name":"Ikhlas A. Sindi","orcid":"0000-0002-2906-3756","position":4,"is_corresponding":false},{"id":1176366,"name":"Mamdouh Eldesoqui","orcid":"0000-0002-6589-4514","position":5,"is_corresponding":false},{"id":1176367,"name":"Mohamed El‐Sherbiny","orcid":"0000-0002-0814-1743","position":6,"is_corresponding":false},{"id":1176707,"name":"Amira Awadalla","orcid":null,"position":7,"is_corresponding":false},{"id":1176708,"name":"Amoura M Aboualnaga","orcid":null,"position":8,"is_corresponding":false},{"id":1176706,"name":"Amira Sarhan","orcid":null,"position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T01:20:00.023537Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}