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Follicular Reconstruction and Neo-Oogenesis in Xenotransplantation of Human Ovarian Isolated Cells Derived From Chemotherapy-Induced Pof Patients Publisher



Khaleghi S1 ; Eivazkhani F2 ; Tavana S2 ; Moini A3, 4 ; Novin MG1 ; Stoyan P5, 6 ; Nazarian H1 ; Fathi R2
Authors
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Authors Affiliations
  1. 1. Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  2. 2. Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
  3. 3. Department of Endocrinology and Female Infertility, Royan Institute of Reproductive Biomedicine, ACECR, Tehran, Iran
  4. 4. Breast Disease Research Center (BDRC), Tehran University of Medical Science, Tehran, Iran
  5. 5. Platform Degenerative Diseases, German Primate Center, GmbH, Leibniz Institute for Primate Research, Gottingen, 37077, Germany
  6. 6. German Center for Cardiovascular Research (DZHK), Partner Site Gottingen, Gottingen, 37077, Germany

Source: Journal of Biological Engineering Published:2023


Abstract

Background: Developing new strategies to restore fertility in patients with chemotherapy-induced Premature Ovarian Failure (Chemo-POF) is important. We aimed to construct an Artificial Ovary (AO) by seeding Human Ovarian Cortical Cells (HOCCs) into Human ovarian Decellularized Cortical Tissue (DCT). We assessed the AO’s ability to produce new ovarian follicles following xenotransplantation to NMRI mice. Material and methods: The DCTs were prepared, and cell removal was confirmed through DNA content, MTT assay, DAPI and H&E staining. Next, HOCCs were isolated from both Chemo-POF and Trans (as a control group) ovarian patients. The HOCCs were characterized using immunostaining (FRAGILIS, Vimentin, and Inhibin α) and real time PCR (DDX4, STELLA, FRAGILIS, Vimentin, FSH-R, KI67) assays. The HOCCs were then seeded into the DCTs and cultured for one week to construct an AO, which was subsequently xenotransplanted into the mice. The existence of active follicles within the AO was studied with H&E and immunofluorescence (GDF9) staining, Real-time PCR (GDF9, ZP3) and hormone analysis (Estradiol, FSH and AMH). Results: The results of gene expression and immunostaining showed that 85–86% of the isolated cells from both Trans and Chemo-POF groups were positive for vimentin, while 2–5% were granulosa cells and OSCs were less than 3%. After xenotransplantation, histological study confirmed the presence of morphologically healthy reconstructed human ovarian follicles. Additionally, immunofluorescence staining of GDF9 and hormonal assay confirmed the presence of secretory-active follicles on the AO. Conclusion: Our findings demonstrate that an artificial ovary produced by seeding HOCCs on DCT can support HOCCs proliferation as well as neo-oogenesis, and enable sex hormone secretion following xenotransplantation. © 2023, The Author(s).
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2. Two-Decade Experience of Royan Institute in Obtaining Mature Oocyte From Cryopreserved Ovarian Tissue: In Vitro and in Vivo Approaches, Reproductive Sciences (2022)
3. Optimizing the Cell Seeding Protocol to Human Decellularized Ovarian Scaffold: Application of Dynamic System for Bio-Engineering, Cell Journal (2019)
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