Ebrahim, N, Al Saihati, HA, Shaman, A, Dessouky, AA, Farid, AS, Hussien, NI, Mostafa, O, Seleem, Y, Sabry, D, Saad, AS, Emam, HT, Hassouna, A, Badr, OAM, Saffaf, BA, Forsyth, NR and Salim, RF (2021) Bone marrow-derived mesenchymal stem cells combined with gonadotropin therapy restore postnatal oogenesis of chemo-ablated ovaries in rats via enhancing very small embryonic-like stem cells. Stem Cell Research and Therapy, 12 (517). ISSN 1757-6512

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Abstract

BACKGROUND: Very small embryonic-like stem cells (VSELs) are a rare population within the ovarian epithelial surface. They contribute to postnatal oogenesis as they have the ability to generate immature oocytes and resist the chemotherapy. These cells express markers of pluripotent embryonic and primordial germ cells.

OBJECTIVE: We aimed to explore the capability of VSELs in restoring the postnatal oogenesis of chemo-ablated rat ovaries treated with bone marrow-derived mesenchymal stem cells (BM-MSCs) combined with pregnant mare serum gonadotropin (PMSG).

METHODS: Female albino rats were randomly assigned across five groups: I (control), II (chemo-ablation), III (chemo-ablation + PMSG), IV (chemo-ablation + MSCs), and V (chemo-ablation + PMSG + MSCs). Postnatal oogenesis was assessed through measurement of OCT4, OCT4A, Scp3, Mvh, Nobox, Dazl4, Nanog, Sca-1, FSHr, STRA8, Bax, miR143, and miR376a transcript levels using qRT-PCR. Expression of selected key proteins were established as further confirmation of transcript expression changes. Histopathological examination and ovarian hormonal assessment were determined.

RESULTS: Group V displayed significant upregulation of all measured genes when compared with group II, III or IV. Protein expression confirmed the changes in transcript levels as group V displayed the highest average density in all targeted proteins. These results were confirmed histologically by the presence of cuboidal germinal epithelium, numerous primordial, unilaminar, and mature Graafian follicles in group V.

CONCLUSION: VSELs can restore the postnatal oogenesis in chemo-ablated ovaries treated by BM-MSCs combined with PMSG.

Item Type: Article
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Uncontrolled Keywords: Ovarian chemo-ablation; MSCs; Postnatal oogenesis; VSELs; Gonadotropins
Subjects: R Medicine > R Medicine (General)
R Medicine > R Medicine (General) > R735 Medical education. Medical schools. Research
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering
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Depositing User: Symplectic
Date Deposited: 13 Oct 2021 14:00
Last Modified: 06 Dec 2021 13:08
URI: https://eprints.keele.ac.uk/id/eprint/10110

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