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Bone marrow-derived mesenchymal stem cells combined with gonadotropin therapy restore postnatal oogenesis of chemoablated ovaries in rats via enhancing very small embryonic-like stem cells

• 2021
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Publication Information
Authors Nesrine Ebrahim1,2, Hajir A. Al Saihati3, Amani Shaman4, Arigue A. Dessouky5, Ayman Samir Farid6
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publication.type Local
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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 (chemoablation
+ 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.