Roles of miR-10a-5p and miR-103a-3p, Regulators of BDNF Expression in Follicular Fluid, in the Outcomes of IVF-ET

Abstract

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays critical roles in the physiological process of oocyte mature and IVF outcomes of patients with infertility. However, the regulation of BDNF expression in the microenvironment surrounding the oocyte is still unknown. We initially predicted some microRNA (miRNA) candidates targeting bdnf with a series of bioinformatics analysis tools to determine the underlying regulatory mechanisms of BDNF, particularly the effect of miRNAs on BDNF expression. Then, we assessed whether the expression of these 14 selected miRNAs was negatively associated with BDNF expression in follicular fluid (FF) samples obtained from mature (>18 mm) or immature (<15 mm) follicles. Finally, we used the candidate miRNAs, miR-103a-3p and miR-10a-5p, to further investigate the relationship between their expression in FF and the outcomes of infertile patients undergoing IVF–ET treatment. The results of the bioinformatics analysis revealed 14 miRNAs that might directly regulate BDNF expression and might have a close relationship with oocyte development. BDNF was expressed at significantly lower levels in FF from immature follicles than in FF from mature follicles, and only the expression of miR-103a-3p and miR-10a-5p was negatively correlated with BDNF expression in FF. Moreover, in another cohort of 106 infertile women undergoing IVF-ET treatment, miR-103a-3p or miR-10a-5p expression predicted the developmental status of the corresponding oocytes in which high expression of miR-103a-3p or miR-10a-5p resulted in a poor quality of embryo on days 3 and 5 during the IVF-ET treatment. In conclusion, our study is the first to show that miR-103a-3p or miR-10a-5p negatively affects the maturation of oocytes by regulating the expression of BDNF in human FF. Additionally, the expression levels of miR-103a-3p or miR-10a-5p in FF may predict the outcomes of IVF, which are helpful for improving embryo selection and consequently the IVF success rate in the clinic.

Decrease in the Ratio proBDNF/BDNF in the Urine of Aging Female Patients with OAB

“…To provide insights in the regulation of proBDNF synthesis, we measured diverse urinary factors and microRNAs known to control the translation of proBDNF mRNA ( Table 5 ). MiR-26b-5p, miR-26a-5p, miR-10a-5p, and miR-103a-3p that bind the 3′UTR sequence of proBDNF mRNA were not expressed differently between control and OAB patients [ 25 , 26 ]. Levels of other miRNAs (miR-15b-5p, miR-142-3p and miR-103a-3p) that control proBDNF expression through downstream or upstream pathways were also not different [ 25 , 27 , 28 ].…”

“…MiR-26b-5p, miR-26a-5p, miR-10a-5p, and miR-103a-3p that bind the 3′UTR sequence of proBDNF mRNA were not expressed differently between control and OAB patients [ 25 , 26 ]. Levels of other miRNAs (miR-15b-5p, miR-142-3p and miR-103a-3p) that control proBDNF expression through downstream or upstream pathways were also not different [ 25 , 27 , 28 ]. On the other hand, concentration of miR-491-5p, which negatively controls MMP-9 expression, was significantly decreased in the OAB group: 0.122 (Q1, Q3: 0.0221, 0.392) vs. 0.533 (Q1,Q3: 0.302, 1.643) in the control group, p < 0.05 ( Figure 1 c) [ 29 ].…”

A single intranasal dose of human mesenchymal stem cell-derived extracellular vesicles after traumatic brain injury eases neurogenesis decline, synapse loss, and BDNF-ERK-CREB signaling

“…However, none of the top 20 highly enriched miRNAs found within hMSCs are known to upregulate BDNF expression ( Kodali et al, 2023 ). Instead, several miRNAs enriched in hMSC-EVs can decrease BDNF concentration, which includes miR-26b ( Caputo et al, 2011 ), miR-10a-5p ( Zhang Q et al, 2021 ), miR-10b-5p ( Müller, 2014 ), and miR-30a-3p ( Mellios et al, 2008 ). Still, the combined effects of the miRNA and protein cargo of hMSC-EVs improving BDNF-ERK-CREB signaling after TBI cannot be ruled out.…”

Analysis of the Resistance of Small Peptides from Periplaneta americana to Hydrogen Peroxide-induced Apoptosis in KGN Cells based on High-throughput miRNA Sequencing

“…Cheng et al found that upregulation of miR-103a-3p promoted chondrocyte proliferation of human osteoarthritis (OA) and inhibited cell apoptosis and in ammatory responses [21]. Zhang et al reported that miR-103a-3p exerted negative in uences on the maturation of oocytes by regulating brain-derived neurotrophic factor (BDNF) expression in human follicular uid [22]. These studies all con rm that miR-103a-3p and miR-214 play an important regulatory role in cell apoptosis and oxidative stress, consistent with the data in the current study.…”