Transcriptomic profiling reveals estradiol and progesterone specific microRNA signatures differentially regulate mRNA targets in vaginal epithelial cells

In the female reproductive tract, epithelial cells act as a protective barrier, defending against sexually transmitted infections. Fluctuating sex hormones 17{beta}-estradiol (E2) and progesterone (P4) impact these cells' functions, with E2 generally protecting against viruses like HIV-1 and HSV-2, while P4 increases susceptibility. However, the mechanisms behind this are not fully understood.

Researchers studied the impact of E2 and P4 on microRNA (miRNA) expression in vaginal epithelial cells (VECs), the body's first line of defense against pathogens. Using next generation sequencing, they found that 13 miRNAs were uniquely regulated by E2, and 102 by P4, with 29 miRNAs overlapping between both treatments.

The top four miRNAs differentially affected by E2 and P4 were validated via RT-qPCR. The miRNAs unique to E2 treatment were linked to adherens junction, tight junction, and chemokine signaling pathways. Meanwhile, miRNAs exclusive to P4 treatment influenced the MAPK signaling pathway. Importantly, several E2- and P4-regulated miRNAs targeted genes involved in the cell cycle pathway.

In summary, the study suggests that hormones E2 and P4 regulate miRNAs that impact genes in pathways related to cell adhesion, growth, development, and innate immune responses. These hormone-regulated miRNAs could potentially serve as therapeutic targets for maintaining the epithelial barrier and regulating pathogen susceptibility in the vaginal tract.