RESUMO
RESEARCH QUESTION: Granulosa cells (GCs) dysfunction plays a crucial role in the pathogenesis of polycystic ovary syndrome (PCOS). It is reported that YTH domain-containing family protein 2 (YTHDF2) is upregulated in mural GCs of PCOS patients. What effect does the differential expression of YTHDF2 have in PCOS patients? DESIGN: Mural GCs and cumulus GCs from 15 patients with PCOS and 15 ovulatory controls and 4 cases of pathological sections in each group were collected. Real-time PCR, Western Blot, immunohistochemistry, and immunofluorescence experiments were conducted to detect gene and protein expression. RNA immunoprecipitation assay was performed to evaluate the binding relationship between YTHDF2 and MSS51. Mitochondrial morphology, cellular ATP and ROS levels and glycolysis-related gene expression were detected after YTHDF2 overexpression or MSS51 inhibition. RESULTS: In the present study, we found that YTHDF2 was upregulated in GCs of PCOS patients while MSS51 was downregulated. YTHDF2 protein can bind to MSS51 mRNA and affect MSS51 expression. The reduction of MSS51 expression or the increase in YTHDF2 expression can lead to mitochondrial damage, reduced ATP levels, increased ROS levels and reduced expression of LDHA, PFKP and PKM. CONCLUSIONS: YTHDF2 may regulate the expression of MSS51, affecting the structure and function of mitochondria in GCs and interfering with cellular glycolysis, which may disturb the normal biological processes of GCs and follicle development in PCOS patients.
Assuntos
Células da Granulosa , Mitocôndrias , Síndrome do Ovário Policístico , Proteínas de Ligação a RNA , Humanos , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Feminino , Células da Granulosa/metabolismo , Células da Granulosa/patologia , Mitocôndrias/metabolismo , Mitocôndrias/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Adulto , Espécies Reativas de Oxigênio/metabolismo , Regulação da Expressão Gênica , Trifosfato de Adenosina/metabolismo , Glicólise/genética , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Our study aimed to examine the shared and distinct structural brain alterations, including cortical thickness(CT) and local gyrification index(LGI), and cognitive impairments between the early course stage of drug-naïve schizophrenia(SZ) and bipolar disorder(BD) patients when compared to healthy controls(HCs), and to further explore the correlation between altered brain structure and cognitive impairments. We included 72 SZ patients, 35 BD patients and 43 HCs. The cognitive function was assessed using the MATRICS Consensus Cognitive Battery. Cerebral cortex analyses were performed with FreeSurfer. Furthermore, any structural aberrations related to cognition impairments were examined. Cognitive impairments existed in SZ and BD patients and were much more severe and widespread in SZ patients, compared to HCs. There were no significant differences in LGI among three groups. Compared to HCs, SZ had thicker cortex in left pars triangularis, and BD showed thinner CT in left postcentral gyrus. In addition, BD showed thinner cortex in left pars triangularis, left pars opercularis, left insula and right fusiform gyrus compared to SZ. Moreover, our results indicated that CT in many brain areas were significantly correlated with cognitive function in HCs, but only CT of left pars triangularis was correlated with impaired social cognition found in SZ. The findings suggest that changes of CT in the left pars triangularis and left postcentral gyrus may be potential pathophysiological mechanisms of the cognition impairments in SZ and BD, respectively, and the divergent CT of partly brain areas in BD vs. SZ may help distinguish them in early phases.