Therefore, this study was aimed to investigate the effects of BMI with EV-linked miRNA expression isolated from follicular fluid in women undergoing IVF treatment.įollicular fluid (otherwise discarded material) was collected during oocyte retrieval from a single follicle ≥18 mm, per patient and centrifuged at 1500×g for 15 min. Investigating EV-linked miRNAs in follicular fluid might help elucidate the mechanisms and pathways by which these modified risk factors that can impact fertility. To the best of our knowledge, no study has examined associations between BMI and EV-linked miRNAs found in follicular fluid. Several studies to date have reported possible associations between BMI and EV-linked miRNA profiles either in adipocytes or serum linking some of these EV-linked miRNAs with pathways of inflammation and insulin resistance ( 31- 34). These EV-linked miRNAs can influence gene expression and may be important for follicular signaling ( 15, 29, 30).
These extracellular vesicle linked microRNAs (EV-linked miRNAs) can be encapsulated within the EV itself, but also associated with the EV extracellularly ( 28). Extracellular vesicles (exosomes, micro-vesicles, and other membrane-bound vesicles) have been detected in almost every biofluid, including follicular fluid ( 22), and can act as a vehicle carrying proteins, messenger RNAs (mRNAs), and microRNAs (miRNAs) ( 27). MicroRNAs are short, non-coding RNA molecules that can post-transcriptionally regulate gene expression ( 24- 26) and can be free-floating or packaged in extracellular vesicles (EV-linked miRNAs). They are nanosized (30-700 nm in diameter) and can contain numerous molecules involved in cell signaling and cell to cell communication, including microRNAs, which are short non-coding RNA molecules (approximately 22 nucleotides long) ( 23). EVs, membrane enclosed structures ( 22), have been identified as a means for intercellular communication between the granulosa cells and oocyte in the follicular fluid ( 15). Follicular fluid is a crucial microenvironment for the developing oocytes, containing hormones, metabolites, ions, proteins, and various biological structures including non-coding RNAs and extracellular vesicles (EVs) ( 14- 21). Theca and granulosa cells create the membrane of the follicle itself, while cumulus cells encapsulate the oocyte ( 13, 14). The ovarian follicle houses the oocyte itself and as it matures, cellular differentiation occurs, creating cellular layers of thecal, mural granulosa, and cumulus cells. Despite the ample epidemiologic evidence, the molecular mechanisms underlying how increased BMI contributes to infertility are still unknown. Women with a BMI ≥ 25 kg/m 2 undergoing IVF have a significantly reduced chance of a clinical pregnancy compared to women with BMI < 25 kg/m 2 ( 10- 12). Studies have shown that an increased BMI and obesity alter follicular development, oocyte maturation, and reduced numbers of oocytes retrieved ( 5- 9). Whereas much has been published about non-modifiable factors associated with outcomes of IVF such as female age, fertility diagnosis, and ovarian reserve, less attention has been devoted to modifiable behavioral risk factors, such as body mass index (BMI) that may influence IVF outcomes ( 2- 4). Despite enormous advances in the technical aspects of IVF, the success rates of the procedure remain relatively low. Human infertility is influenced by a broad range of physical, hormonal, genetic and environmental stressors ( 1).
0 kommentar(er)
