Impaired telomere length and telomerase activity in peripheral blood leukocytes and granulosa cells in patients with biochemical primary ovarian insufficiency

Xu, Xiaofei; Chen, Xinxia; Zhang, Xiruo; Liu, Yi‐Xun; Zhao, Wei; Wang, Peng; Du, Yanzhi; Qin, Yingying; Chen, Zi‐Jiang

doi:10.1093/humrep/dew283

Cited by 59 publications

(62 citation statements)

References 30 publications

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“…In this case, patients with biochemical POI were classified with FSH levels ranging from 10 to 40 IU/L and regular menstruation, also representing an intermediate stage of POI in which the primordial follicle pool has not been fully depleted. Despite the nature of the POI groups and the cells used to assess telomere content in these previous studies, both are compatible with our results and lead to the hypothesis that telomere length plays an important role in the pathophysiology of the disease (40).…”

Section: Discussionsupporting

confidence: 92%

Skewed X-chromosome inactivation and shorter telomeres associate with idiopathic premature ovarian insufficiency

Furtado

Luchiari

Pedroso

et al. 2018

Fertility and Sterility

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Section: Discussionsupporting

confidence: 92%

Skewed X-chromosome inactivation and shorter telomeres associate with idiopathic premature ovarian insufficiency

Furtado

Luchiari

Pedroso

et al. 2018

Fertility and Sterility

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“…The clinical characteristics of bPOI and control women are shown in Tables 1 and 2. Granulosa cells and plasma were isolated from each participant and stored at −80°C until use as described previously (Dang, Zhao et al, 2015; Dang, Wang et al, 2018; Xu et al, 2017).…”

Section: Methodsmentioning

confidence: 99%

MicroRNA‐127‐5p impairs function of granulosa cells via HMGB2 gene in premature ovarian insufficiency

Zhang

Dang

Liu

et al. 2020

Journal Cellular Physiology

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Distinct microRNA (miRNA) profiles have been reported in premature ovarian insufficiency (POI), but their functional relevance in POI is not yet clearly stated. In this study, aberrant expressions of miR‐127‐5p and high mobility group box 2 (HMGB2) were observed by microarrays in granulosa cells (GCs) from biochemical POI (bPOI) women and further confirmed by a quantitative reverse‐transcription polymerase chain reaction. Immortalized human granulosa cell line and mouse primary ovarian GCs were used for functional validation. Orthotopic mouse model was established to examine the role of miR‐127‐5p in vivo. Finally, the expression of miR‐127‐5p was measured in the plasma of bPOI women. The receiver operating characteristic curve analysis was performed to determine the indicative role of miR‐127‐5p for ovarian reserve. Results showed the upregulation of miR‐127‐5p was identified in GCs from bPOI patients. It inhibited GCs proliferation and impaired DNA damage repair capacity through targeting HMGB2, which was significantly downregulated in GCs from the same cohort of cases. miR‐127‐5p was confirmed to attenuate DNA repair capability via HMGB2 in mouse ovary in vivo. Intriguingly, the upexpression of miR‐127‐5p was also detected in plasma of bPOI individuals, suggesting that miR‐127‐5p could be a promising indicator for bPOI. Taken together, our results discovered the deleterious effects of miR‐127‐5p on GCs function and its predictive value in POI process. The target gene HMGB2 could be considered as a new candidate for POI. This study highlights the importance of DNA repair capacity for ovarian function and sheds light on the epigenetic mechanism in the pathogenicity of POI.

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“…The clinical characteristics of bPOI and control women were shown in Table 1 . Granulosa cells were isolated from each participant and stored at −80 ℃ until processed for RNA extraction as described previously 58 .…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-379-5p is associated with biochemical premature ovarian insufficiency through PARP1 and XRCC6

et al. 2018

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Premature ovarian insufficiency (POI) imposes great challenges on women’s fertility and lifelong health. POI is highly heterogeneous and encompasses occult, biochemical, and overt stages. MicroRNAs (miRNAs) are negative regulators of gene expression, whose roles in physiology and diseases like cancers and neurological disorders have been recognized, but little is known about the miRNAs profile and functional relevance in biochemical POI (bPOI). In this study, the expression of miRNAs and mRNAs in granulosa cells (GCs) of bPOI women was determined by two microarrays, respectively. MiR-379-5p, PARP1, and XRCC6 were differentially expressed in GCs of bPOI as revealed by microarrays. Subsequently, functional studies demonstrated that miR-379-5p overexpression inhibited granulosa cell proliferation and attenuated DNA repair efficiency. Furthermore, both PARP1 and XRCC6 showed lower levels in GCs from patients with bPOI and were identified as executives of miR-379-5p. Therefore, our data first uncovered potentially pathogenic miR-379-5p and two novel targets PARP1 and XRCC6 in bPOI, which corroborated the significance of DNA repair for POI, and brought up an epigenetic explanation for the disease.

show abstract

Impaired telomere length and telomerase activity in peripheral blood leukocytes and granulosa cells in patients with biochemical primary ovarian insufficiency

Cited by 59 publications

References 30 publications

Skewed X-chromosome inactivation and shorter telomeres associate with idiopathic premature ovarian insufficiency

Skewed X-chromosome inactivation and shorter telomeres associate with idiopathic premature ovarian insufficiency

MicroRNA‐127‐5p impairs function of granulosa cells via HMGB2 gene in premature ovarian insufficiency

MicroRNA-379-5p is associated with biochemical premature ovarian insufficiency through PARP1 and XRCC6

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