Circular DDX10 is associated with ovarian function and assisted reproductive technology outcomes through modulating the proliferation and steroidogenesis of granulosa cells

Cai, Hong-Cai; Chang, Tianli; Li, Yamin; Jia, Yinzhao; Li, Huiying; Zhang, Mengdi; Su, Ping; Zhang, Ling; Xiang, Wenpei

doi:10.18632/aging.202699

Cited by 12 publications

(8 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…α-Synuclein may synergistically interact with β-amyloid and tau protein to promote their accumulation [ 71 ] and may be involved in the pathogenesis of AD in addition to synucleinopathie (e.g., Parkinson’s disease) [ 72 , 73 ]. DDX10 may also affect ovarian senescence [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

Inter- and intra-chromosomal modulators of the APOE ɛ2 and ɛ4 effects on the Alzheimer’s disease risk

et al. 2022

View full text Add to dashboard Cite

The mechanisms of incomplete penetrance of risk-modifying impacts of apolipoprotein E (APOE) ε2 and ε4 alleles on Alzheimer’s disease (AD) have not been fully understood. We performed genome-wide analysis of differences in linkage disequilibrium (LD) patterns between 6,136 AD-affected and 10,555 AD-unaffected subjects from five independent studies to explore whether the association of the APOE ε2 allele (encoded by rs7412 polymorphism) and ε4 allele (encoded by rs429358 polymorphism) with AD was modulated by autosomal polymorphisms. The LD analysis identified 24 (mostly inter-chromosomal) and 57 (primarily intra-chromosomal) autosomal polymorphisms with significant differences in LD with either rs7412 or rs429358, respectively, between AD-affected and AD-unaffected subjects, indicating their potential modulatory roles. Our Cox regression analysis showed that minor alleles of four inter-chromosomal and ten intra-chromosomal polymorphisms exerted significant modulating effects on the ε2- and ε4-associated AD risks, respectively, and identified ε2-independent (rs2884183 polymorphism, 11q22.3) and ε4-independent (rs483082 polymorphism, 19q13.32) associations with AD. Our functional analysis highlighted ε2- and/or ε4-linked processes affecting the lipid and lipoprotein metabolism and cell junction organization which may contribute to AD pathogenesis. These findings provide insights into the ε2- and ε4-associated mechanisms of AD pathogenesis, underlying their incomplete penetrance.

show abstract

Section: Discussionmentioning

confidence: 99%

Inter- and intra-chromosomal modulators of the APOE ɛ2 and ɛ4 effects on the Alzheimer’s disease risk

et al. 2022

View full text Add to dashboard Cite

show abstract

“…194 upregulated and 207 downregulated circRNAs were enriched in oxidation–reduction, steroid hormone production, and insulin secretion pathways throughout aging. According to Hongcai Cai [ 26 ], circDDX10 levels in GCs steadily declined with aging and were positively linked with AMH and AFC. CircDDX10 was found to be a unique biomarker for predicting ART outcomes and was connected to the quantity of oocytes obtained and good-quality embryo rates.…”

Section: Discussionmentioning

confidence: 99%

Exosomal circ_0008285 in follicle fluid regulates the lipid metabolism through the miR-4644/ LDLR axis in polycystic ovary syndrome

Yu,

Wang,

Zhang

et al. 2023

J Ovarian Res

View full text Add to dashboard Cite

Purpose Exosomal circRNA, as an essential mediator of the follicular microenvironment, has been implicated in the etiological and pathobiological studies of polycystic ovarian syndrome (PCOS). This study aimed to determine abnormal circular RNA (circRNA) expression profiles in follicle fluid (FF) exosomes in patients with PCOS and identify the role of circ_0008285/microRNA (miR)-4644/low-density lipoprotein receptor (LDLR) axis in PCOS. Methods Sixty-seven women undergoing IVF/ICSI, 31 PCOS patients and 36 non-PCOS patients were included in the cohort study. The circRNA expression profiles of FF exosomes in PCOS (n = 3) and control group (n = 3) were compared by RNA sequencing. In an additional cohort (PCOS:28 vs Control:33), the mRNA expression levels of four circRNAs from FF exosomes were further verified by qRT-PCR. Bioinformatic analysis and dual luciferase reporter gene assay verified the relationship between circ_0008285 and miR-4644 and between miR-4644 and LDLR. KGN cells were infected with sh-circ0008285 and transfected with miR-4644 mimic to verify their roles in lipid metabolism. Results Four circRNAs showed significantly different expressions. Circ_0044234 was overexpressed in PCOS patients, while circ_0006877, circ_0013167 and circ0008285 were decreased in PCOS. Among four differentially expressed circRNAs, circ0008285 was enriched in lipoprotein particle receptor activity and cholesterol metabolism pathway by GO and KEGG pathway analyses. Luciferase assay confirmed the competing endogenous RNA (ceRNA) network circ_0008285/miR-4644 /LDLR. The intercellular experiments on circ_0008285 and its reduction in KGN cells showed that the consumption of circ_0008285 in exosomes could increase the expression of miR-4644 in recipient cells and inhibit the expression of LDLR, as well as increase free fatty acid secretion. Conclusion Circ_0008285 can combine with miR-4644 to promote the expression of LDLR and affect the cholesterol metabolism of ovarian granulosa cells in PCOS. Our findings revealed the ceRNA network of circ_0008285 and provided a new path to investigate lipid metabolism abnormalities in PCOS.

show abstract

“…Many positive regulatory indicators predict the ART outcomes in human granulosa cells, such as circRNA [23], AQP7 [24] and telomerase activity [25]. As negative regulatory indicators, hsa-miR-320a-3p and hsa-miR-483-5p, can be combined with positive regulatory indicators to make the prediction results more reliable.…”

Section: Discussionmentioning

confidence: 99%

hsa-miR-320a-3p and hsa-miR-483-5p levels in human granulosa cells: promising bio-markers of live birth after IVF/ICSI

Liu

Mei

Yang

et al. 2022

Reprod Biol Endocrinol

Self Cite

View full text Add to dashboard Cite

Background MicroRNAs (miRNAs) are considered potential biomarkers for various diseases. This study investigated whether hsa-miR-320a-3p and hsa-miR-483-5p levels in human ovarian granulosa cells derived from follicular fluids are associated with embryo developmental competence. Methods We collected 195 granulosa cells samples and analyzed the treatment outcomes in patients undergoing in vitro fertilization (n = 147) or intracytoplasmic sperm injection (n = 48) cycles. The hsa-miR-320a-3p and hsa-miR-483-5p levels in granulosa cells were measured using quantitative reverse transcription-polymerase chain reaction. Results Patients were subdivided into four groups according to the granulosa cells hsa-miR-320a-3p and hsa-miR-483-5p levels quartiles (Q1–Q4). Embryo developmental competence was compared using the chi-square test. Patients in Q3 were less likely to achieve a normal fertilization rate for in vitro fertilization and blastocyst formation than those in Q1 as they expressed high levels of hsa-miR-320a-3p and hsa-miR-483-5p (P < 0.05). Patients in Q3 and Q4 were less likely to achieve a good-quality embryo as they expressed high levels of hsa-miR-483-5p and hsa-miR-320a-3p (P < 0.05). The hsa-miR-320a-3p and hsa-miR-483-5p levels were not associated with clinical pregnancy. However, multiple regression analysis indicated that in Q3 and Q4 intervals had experienced a decreased chance of live birth due to high expression levels of hsa-miR-320a-3p and hsa-miR-483-5p levels. The relative hsa-miR-320a-3p expression levels in granulosa cells were weakly and positively correlated with the patient age (P = 0.0033). Moreover, both the basal follicle stimulating hormone (P = 0.0003) and ovarian stimulation protocols (P = 0.006 and P = 0.004) significantly and positively affected hsa-miR-320a-3p levels. The days of stimulation was negatively correlated with the relative hsa-miR-320a-3p expression level (P = 0.047). Conclusions The hsa-miR-320a-3p and hsa-miR-483-5p levels in human granulosa cells negatively correlated with the good-quality embryo rate and live birth, indicating that hsa-miR-320a-3p and hsa-miR-483-5p can be used as potential negative indicators to predict good-quality embryos and live births.

show abstract

Circular DDX10 is associated with ovarian function and assisted reproductive technology outcomes through modulating the proliferation and steroidogenesis of granulosa cells

Cited by 12 publications

References 57 publications

Inter- and intra-chromosomal modulators of the APOE ɛ2 and ɛ4 effects on the Alzheimer’s disease risk

Inter- and intra-chromosomal modulators of the APOE ɛ2 and ɛ4 effects on the Alzheimer’s disease risk

Exosomal circ_0008285 in follicle fluid regulates the lipid metabolism through the miR-4644/ LDLR axis in polycystic ovary syndrome

hsa-miR-320a-3p and hsa-miR-483-5p levels in human granulosa cells: promising bio-markers of live birth after IVF/ICSI

Contact Info

Product

Resources

About