MiRNA and menstrual cycle

Study question: Do ovarian hormone levels influence cell-free or “circulating” microRNA (cf-miRNA) levels across the menstrual cycle? Summary answer: This exploratory study suggests that hormonal levels fluctuations throughout the menstrual cycle may alter cf-miRNAs levels. Study design, size, duration: A prospective, monocentric study conducted between March and November 2021. Since this a pilot study, sample size was based on feasibility as well as previous, similar human studies conducted in different tissues. A total of 20 subjects were involved in the study. Participants/materials, setting, methods: We conducted an exploratory study where blood samples were collected from sixteen eumenorrheic females in the early follicular phase, the ovulation phase and the mid-luteal phase of the menstrual cycle. Ovarian hormones oestrogen, progesterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in serum by electrochemiluminescence. The levels of 179 plasma-enriched miRNAs were profiled using a PCR-based panel, including stringent internal and external controls to account for the potential differences in RNA extraction and reverse-transcription stemming from low-RNA input samples. Main results and the role of chance: This exploratory study suggests that cf-miRNAs may play an active role in the regulation of the female cycle by mediating the expression of genes fluctuating with hormonal changes. Linear mixed-models adjusted for the relevant variables showed numerous associations between phases of the menstrual cycle, ovarian hormones and plasma cf-miRNA levels. Validated gene targets of the cf-miRNAs varying with the menstrual cycle were enriched within the female reproductive tissues and primarily involved in cell proliferation and apoptosis.