Background
The loss of ovarian function in women, referred to as premature ovarian insufficiency (POI), is associated with a series of concomitant diseases. POI is genetically heterogeneous, and in most cases, the etiology is unknown.
Methods
Whole-exome sequencing (WES) was performed on DNA samples obtained from patients with POI, and Sanger sequencing was used to validate the detected potentially pathogenic variants. An in silico analysis was carried out to predict the pathogenicity of the variants.
Results
We recruited 24 patients with POI and identified variants in POI-related genes in 14 patients, including bi-allelic mutations in DNAH6, HFM1, EIF2B2, BNC, and LRPPRC and heterozygous variants in BNC1, EIF2B4, FOXL2, MCM9, FANCA, ATM, EIF2B3, and GHR. No variants in the above genes were detected in the WES data obtained from 29 women in a control group without POI. Determining a clear genetic etiology could significantly increase patient compliance with appropriate intervention strategies.
Conclusions
Our study confirmed that POI is a genetically heterogeneous condition and that whole-exome sequencing is a powerful tool for determining its genetic etiology. The results of this study will aid researchers and clinicians in genetic counseling and suggests the potential of WES for the detection of POI and thus early interventions for patients with POI.
Polycystic ovary syndrome (PCOS) is an endocrine disease that affects the health of many women. Circular RNAs (circRNAs) are associated with the occurrence and progression of PCOS. This study aimed to explore the function of circ_RANBP9 in PCOS. First, the circ_RANBP9 level was found to be increased in the plasma of patients with PCOS and ovarian granulosa cells (GCs) using Reverse Transcription-Quantitative Polymerase Chain Reaction (RT-qPCR). In GCs, loss of circ_RANBP9 decelerated proliferation and accelerated apoptosis of KGN and COV434 cells, as determined by MTT assay, colony formation assay, and flow cytometry. Furthermore, bioinformatics analysis showed that circ_RANBP9 and XIAP can be targeted by the microRNA, miR-136-5p. Luciferase reporter assay and RNA pull-down assay further verified the interaction between miR-136-5p and circ_RANBP9 or XIAP. Importantly, knockdown of circ_RANBP9 suppressed proliferation and promoted apoptosis of KGN and COV434 cells, whereas inhibition of miR-136-5p reversed these effects. Additionally, XIAP abolished the repression of proliferation and acceleration of apoptosis induced by miR-136-5p. The promotion of apoptosis was accompanied by upregulation of caspase-3 and Bax, and downregulation of Bcl-2, as estimated by western blotting. In conclusion, silencing of circ_RANBP9 inhibited GC proliferation and facilitated apoptosis by mediating the miR-136-5p/XIAP pathway. These findings provide a new theoretical basis for screening and treatment of PCOS.
Increasing evidence suggests that an exaggerated maternal systemic inflammatofrery response may play a central role in the pathogenesis of preeclampsia (PE). Considering the growing evidence on microRNAs (miRNAs) and tissue-specific regulators of gene expression, we investigated the potential association of miR-210 and forkhead box p3 (Foxp3) in preeclamptic patients. Serum levels of the cytokines interleukin (IL)-6, IL-10, IL-17, and transforming grown factor-β1 were detected with ELISA. Reverse-transcription-quantitative polymerase chain reaction was performed to detect mRNA expression for maternal placenta retinoic acid-related orphan receptor C, Foxp3 and miRNA (miR)-210. Foxp3 protein expression was evaluated by western blot analysis. Serum levels of cytokines IL-10 were significantly lower in preeclamptic patients than in normal pregnant women. mRNA expression of Foxp3 was significantly lower in placenta of PE. mRNA expression of miR-210 was significantly increased in PE. Results of western blot analysis indicated that Foxp3 protein expression was lower in PE than in normal pregnant women. Our data suggest that PE manifests as a decreased number of regulatory T cells (Tregs), which regulate maternal tolerance of the fetus. In placenta from women with PE, compared with normal pregnant women, mRNA expression of Foxp3 was significantly decreased, and expression of miR-210 was significantly increased.
Objective
In this study, we investigated the effect of thyroid‐stimulating hormone (TSH) level on the outcomes of in vitro fertilization (IVF) in patients with polycystic ovary syndrome (PCOS).
Methods
Data pertaining to 60 patients who underwent IVF between May 2017 and May 2018 were included in the study. Thirty‐two patients were diagnosed as PCOS (PCOS group) and 28 patients had tubal infertility (control group). Serum and follicular fluid TSH levels and follicular cyclic AMP (cAMP) level were detected by ELISA. TSH receptor (TSHR) expression level in granulosa cells was quantified by RT‐PCR and Western blot.
Results
In the PCOS group, oocyte maturation rate and fertilization rate were significantly lower than in the control group. Serum and follicular fluid TSH levels and ovarian cAMP level were higher in the PCOS group with an upregulation of ovarian TSHR. On multivariate linear regression analysis, fertilization rate showed a negative correlation with TSH levels in serum (B = −0.106, P = 0.005) and follicular fluid (B = −0.107, P = 0.001).
Conclusion
In PCOS patients, TSH levels, both in serum and follicular fluid, were negatively correlated with IVF oocyte maturation rate and fertilization rate. The effect of TSH on controlled ovarian hyperstimulated oocyte growth was likely mediated by the TSHR/cAMP signaling pathway.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.