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Depletion of GPSM1 enhances ovarian granulosa cell apoptosis via cAMP-PKA-CREB pathway in vitro
Xuefeng Wang
The third affiliated hospital of southern medical university
Corresponding Author
ORCiD: https://orcid.org/0000-0003-2455-9442
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This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Journal of Ovarian Research.
Background Genetic causes of premature ovarian insufficiency (POI) account for approximately 20~25% of patients. So far, only a few genes have been identified.
Results Here, we first identified the c.1840C>A on G-protein signaling modulator 1 (GPSM1) as a susceptibility locus for POI in 10 sporadic POI patients by whole-exome sequencing. The frequency of GPSM1 c.1840C>A was then verified as 3/20 in a POI sample of 20 patients (including the above 10 patients) by Sanger sequencing. RT-PCR and western blot analysis showed the expression of GPSM1 in rat ovaries was increased in the large antral follicle stage compared to the primordial follicle stage (P<0.01). The cell proliferation assay (CCK8) and flow cytometry suggested that the small-interfering RNA-induced silencing of Gpsm1 significantly increased apoptosis and decreased proliferation of rat ovarian granulosa cells (GCs) (P<0.01). Furthermore, suppression of Gpsm1 in GCs reduced levels of cAMP, PKAc, p-CREB as well as the ratio of Bcl-2/Bax, and increased the expression of Caspase-3 and Cleaved Caspase-3 (P<0.01).
Conclusions In summary, this study identified a susceptibility variant GPSM1 c.1840C>A of POI for the first time. Gpsm1 was related to rat follicle development, and silencing of Gpsm1 increased apoptosis and decreased proliferation in rat GCs, possibly through inhibition of the cAMP-PKA-CREB pathway.
Keywords
premature ovarian insufficiency, whole-exome sequencing, GPSM1, ovarian granulosa cell, cAMP-PKA-CREB pathway
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CURRENT STATUS: Published
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Posted 23 Sep, 2020
Published
On 21 Nov, 2020
No community comments so far
Editorial decision: Accept
On 03 Nov, 2020
Reviewers invited
Invitations sent on 05 Oct, 2020
Editor assigned
On 21 Sep, 2020
Submission checks complete
On 20 Sep, 2020
Editor invited
On 20 Sep, 2020
No comments provided
Editorial decision: Major revision
On 10 Sep, 2020
Review #1 received
Received 04 May, 2020
Reviewer #1 agreed
On 17 Apr, 2020
Reviewers invited
Invitations sent on 27 Mar, 2020
First submitted
On 24 Mar, 2020
Editor assigned
On 24 Mar, 2020
Submission checks complete
On 23 Mar, 2020
Editor invited
On 23 Mar, 2020
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Subject Areas
Cancer Biology
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This preprint is under consideration at Journal of Ovarian Research. A preprint is 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
Depletion of GPSM1 enhances ovarian granulosa cell apoptosis via cAMP-PKA-CREB pathway in vitro
Xuefeng Wang
The third affiliated hospital of southern medical university
Corresponding Author
ORCiD: https://orcid.org/0000-0003-2455-9442
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 23 Sep, 2020
Published
On 21 Nov, 2020
No community comments so far
Editorial decision: Accept
On 03 Nov, 2020
Reviewers invited
Invitations sent on 05 Oct, 2020
Editor assigned
On 21 Sep, 2020
Submission checks complete
On 20 Sep, 2020
Editor invited
On 20 Sep, 2020
No comments provided
Editorial decision: Major revision
On 10 Sep, 2020
Review #1 received
Received 04 May, 2020
Reviewer #1 agreed
On 17 Apr, 2020
Reviewers invited
Invitations sent on 27 Mar, 2020
First submitted
On 24 Mar, 2020
Editor assigned
On 24 Mar, 2020
Submission checks complete
On 23 Mar, 2020
Editor invited
On 23 Mar, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cancer Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Journal of Ovarian Research.
Background Genetic causes of premature ovarian insufficiency (POI) account for approximately 20~25% of patients. So far, only a few genes have been identified.
Results Here, we first identified the c.1840C>A on G-protein signaling modulator 1 (GPSM1) as a susceptibility locus for POI in 10 sporadic POI patients by whole-exome sequencing. The frequency of GPSM1 c.1840C>A was then verified as 3/20 in a POI sample of 20 patients (including the above 10 patients) by Sanger sequencing. RT-PCR and western blot analysis showed the expression of GPSM1 in rat ovaries was increased in the large antral follicle stage compared to the primordial follicle stage (P<0.01). The cell proliferation assay (CCK8) and flow cytometry suggested that the small-interfering RNA-induced silencing of Gpsm1 significantly increased apoptosis and decreased proliferation of rat ovarian granulosa cells (GCs) (P<0.01). Furthermore, suppression of Gpsm1 in GCs reduced levels of cAMP, PKAc, p-CREB as well as the ratio of Bcl-2/Bax, and increased the expression of Caspase-3 and Cleaved Caspase-3 (P<0.01).
Conclusions In summary, this study identified a susceptibility variant GPSM1 c.1840C>A of POI for the first time. Gpsm1 was related to rat follicle development, and silencing of Gpsm1 increased apoptosis and decreased proliferation in rat GCs, possibly through inhibition of the cAMP-PKA-CREB pathway.
Figure 1
Figure 2
Figure 3
Figure 4