Depletion of GPSM1 enhances ovarian granulosa cell apoptosis via cAMP-PKA-CREB pathway in vitro
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.
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Posted 23 Sep, 2020
On 21 Nov, 2020
On 03 Nov, 2020
Invitations sent on 05 Oct, 2020
On 21 Sep, 2020
On 20 Sep, 2020
On 20 Sep, 2020
On 10 Sep, 2020
Received 04 May, 2020
On 17 Apr, 2020
Invitations sent on 27 Mar, 2020
On 24 Mar, 2020
On 24 Mar, 2020
On 23 Mar, 2020
On 23 Mar, 2020
Depletion of GPSM1 enhances ovarian granulosa cell apoptosis via cAMP-PKA-CREB pathway in vitro
Posted 23 Sep, 2020
On 21 Nov, 2020
On 03 Nov, 2020
Invitations sent on 05 Oct, 2020
On 21 Sep, 2020
On 20 Sep, 2020
On 20 Sep, 2020
On 10 Sep, 2020
Received 04 May, 2020
On 17 Apr, 2020
Invitations sent on 27 Mar, 2020
On 24 Mar, 2020
On 24 Mar, 2020
On 23 Mar, 2020
On 23 Mar, 2020
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