Follicular Fluid microRNAs in Ovarian Aging and Reproduction

There is a substantial gap in understanding how these miRNAs operate in humans, especially in a non-invasive or minimally invasive context.

Specifically:

• The role of exosomal miRNAs in follicular fluid (FF) in human ovarian aging is not well defined.
• Few studies have directly compared miRNA expression profiles in FF across age groups using high-throughput sequencing.
• There is limited evidence linking specific FF miRNAs to oocyte quality or IVF success rates.
• No validated non-invasive biomarkers based on FF exosomal miRNA currently exist for predicting IVF outcomes, especially in women of advanced reproductive age.

This study seeks to address these knowledge gaps by identifying and validating exosomal miRNA signatures in FF that are associated with maternal age and IVF outcomes. The most relevant preliminary data come from preclinical rodent studies performed by our research team:

• miRNA profiling in aged vs. young mouse ovarian tissues demonstrated clear age-associated changes in miRNA expression.
• Gene target analyses revealed that these miRNAs are likely to regulate critical signaling pathways involved in ovarian aging (e.g., FoxO, mTOR, PI3k/Akt).
• These results support the biological plausibility that similar miRNA changes could occur in human follicular environments and impact oocyte competence.

Although direct human data from FF is not yet available, the team has validated methods for exosome isolation from biofluids, miRNA sequencing, and in vitro assays. These tools are now being applied to the human FF samples collected during IVF cycles, making this study a logical and feasible extension of our previous work.

Inclusion criteria

• Women undergoing IVF treatment due to male factor infertility or nonovarian causes.
• Age groups: younger women <31 years and older women >38 years.
• Regular menstrual cycles.
• Willing and able to provide informed consent.

Exclusion criteria

• Minors (under 18 years) and women aged 32-37 years
• Diagnosis of polycystic ovarian syndrome (PCOS).
• History of recurrent pregnancy loss.
• Presence of endometriosis.
• Diagnosis of ovarian insufficiency.
• Metabolic disorders (e.g., diabetes).
• History of ovarian surgery or chemotherapy.
• Any condition that might impact follicular fluid quality or IVF outcomes.