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Background: Translational studies have explored the therapeutic potential and feasibility of mesenchymal stem cells (MSCs) in several degenerative diseases; however, mechanistic studies of the function of these cells have been insufficient. As ovarian failure causes anovulation as well as ovarian steroid hormonal imbalances, the specific aims of this study were to analyze the therapeutic role of placenta-derived MSCs (PD-MSCs) in an ovarian failure ovariectomy (OVX) rat model and evaluate whether PD-MSC transplantation (Tx) improved folliculogenesis and oocyte maturation in the injured ovary through PI3K/Akt and FOXO signaling.
Methods: Blood and ovary tissue were collected and analyzed after various PD-MSC Tx treatments in an ovariectomized rat model. Changes in the expression of folliculogenesis- and ovary regeneration-related genes induced by PD-MSC treatments were analyzed by qRT-PCR, Western blotting, and histological analysis.
Results: The levels of hormones related to ovary function were significantly increased in the PD-MSC Tx groups compared with those in the nontransplantation group (NTx). The follicle numbers in the ovarian tissues were increased along with increased expression of genes related to folliculogenesis in the PD-MSC Tx groups compared with NTx groups. Furthermore, Tx PD-MSCs induced follicle maturation by increasing the phosphorylation of GSK3 beta and FOXO3 (p<0.05) and shifting the balance of growth and apoptosis in oocytes.
Conclusions: Taken together, these results show that PD-MSC Tx can restore ovarian function and induce ovarian folliculogenesis via the PI3K/Akt and FOXO signaling pathway.
Keywords
Placenta-derived stem cells, ovary function, oocyte survival, PI3K/Akt, FOXO3a
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CURRENT STATUS: Published
View the published article at Stem Cell Research & Therapy.
No community comments so far
Editorial decision: Accept
On 13 Sep, 2020
Review #3 received
Received 12 Sep, 2020
Reviewer #3 agreed
On 06 Sep, 2020
Review #1 received
Received 06 Sep, 2020
Reviewer #2 agreed
On 05 Sep, 2020
Review #2 received
Received 05 Sep, 2020
Reviewers invited
Invitations sent on 04 Sep, 2020
Reviewer #1 agreed
On 04 Sep, 2020
Editor assigned
On 03 Sep, 2020
Submission checks complete
On 02 Sep, 2020
Editor invited
On 02 Sep, 2020
Version 2
Posted 06 Aug, 2020
No comments provided
Editorial decision: Minor Revision
On 07 Aug, 2020
Review #3 received
Received 03 Aug, 2020
Reviewers invited
Invitations sent on 03 Aug, 2020
Reviewer #1 agreed
On 03 Aug, 2020
Reviewer #2 agreed
On 03 Aug, 2020
Reviewer #3 agreed
On 03 Aug, 2020
Review #2 received
Received 03 Aug, 2020
Review #1 received
Received 03 Aug, 2020
Editor assigned
On 31 Jul, 2020
Submission checks complete
On 30 Jul, 2020
Editor invited
On 30 Jul, 2020
No comments provided
Editorial decision: Major Revision
On 08 Jun, 2020
Review #3 received
Received 05 Jun, 2020
Reviewer #3 agreed
On 04 Jun, 2020
Review #2 received
Received 30 May, 2020
Reviewer #2 agreed
On 22 May, 2020
Reviewer #1 agreed
On 20 May, 2020
Review #1 received
Received 20 May, 2020
Reviewers invited
Invitations sent on 19 May, 2020
Editor assigned
On 07 May, 2020
Editor invited
On 06 May, 2020
Submission checks complete
On 03 May, 2020
First submitted
On 30 Apr, 2020
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Subject Areas
Stem Cell & Developmental Cell Biology
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A new preprint design is coming!
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See the published version of this preprint at Stem Cell Research & Therapy.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
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Prescreen
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Complete author information
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Potential risks to human health
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Peer Review Timeline
CURRENT STATUS: Published
View the published article at Stem Cell Research & Therapy.
No community comments so far
Editorial decision: Accept
On 13 Sep, 2020
Review #3 received
Received 12 Sep, 2020
Reviewer #3 agreed
On 06 Sep, 2020
Review #1 received
Received 06 Sep, 2020
Reviewer #2 agreed
On 05 Sep, 2020
Review #2 received
Received 05 Sep, 2020
Reviewers invited
Invitations sent on 04 Sep, 2020
Reviewer #1 agreed
On 04 Sep, 2020
Editor assigned
On 03 Sep, 2020
Submission checks complete
On 02 Sep, 2020
Editor invited
On 02 Sep, 2020
Version 2
Posted 06 Aug, 2020
No comments provided
Editorial decision: Minor Revision
On 07 Aug, 2020
Review #3 received
Received 03 Aug, 2020
Reviewers invited
Invitations sent on 03 Aug, 2020
Reviewer #1 agreed
On 03 Aug, 2020
Reviewer #2 agreed
On 03 Aug, 2020
Reviewer #3 agreed
On 03 Aug, 2020
Review #2 received
Received 03 Aug, 2020
Review #1 received
Received 03 Aug, 2020
Editor assigned
On 31 Jul, 2020
Submission checks complete
On 30 Jul, 2020
Editor invited
On 30 Jul, 2020
No comments provided
Editorial decision: Major Revision
On 08 Jun, 2020
Review #3 received
Received 05 Jun, 2020
Reviewer #3 agreed
On 04 Jun, 2020
Review #2 received
Received 30 May, 2020
Reviewer #2 agreed
On 22 May, 2020
Reviewer #1 agreed
On 20 May, 2020
Review #1 received
Received 20 May, 2020
Reviewers invited
Invitations sent on 19 May, 2020
Editor assigned
On 07 May, 2020
Editor invited
On 06 May, 2020
Submission checks complete
On 03 May, 2020
First submitted
On 30 Apr, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Stem Cell & Developmental Cell Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Stem Cell Research & Therapy.
Background: Translational studies have explored the therapeutic potential and feasibility of mesenchymal stem cells (MSCs) in several degenerative diseases; however, mechanistic studies of the function of these cells have been insufficient. As ovarian failure causes anovulation as well as ovarian steroid hormonal imbalances, the specific aims of this study were to analyze the therapeutic role of placenta-derived MSCs (PD-MSCs) in an ovarian failure ovariectomy (OVX) rat model and evaluate whether PD-MSC transplantation (Tx) improved folliculogenesis and oocyte maturation in the injured ovary through PI3K/Akt and FOXO signaling.
Methods: Blood and ovary tissue were collected and analyzed after various PD-MSC Tx treatments in an ovariectomized rat model. Changes in the expression of folliculogenesis- and ovary regeneration-related genes induced by PD-MSC treatments were analyzed by qRT-PCR, Western blotting, and histological analysis.
Results: The levels of hormones related to ovary function were significantly increased in the PD-MSC Tx groups compared with those in the nontransplantation group (NTx). The follicle numbers in the ovarian tissues were increased along with increased expression of genes related to folliculogenesis in the PD-MSC Tx groups compared with NTx groups. Furthermore, Tx PD-MSCs induced follicle maturation by increasing the phosphorylation of GSK3 beta and FOXO3 (p<0.05) and shifting the balance of growth and apoptosis in oocytes.
Conclusions: Taken together, these results show that PD-MSC Tx can restore ovarian function and induce ovarian folliculogenesis via the PI3K/Akt and FOXO signaling pathway.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
This is a list of supplementary files associated with this preprint. Click to download.
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