MiR-378b Modulates -Induced Upper Genital Tract Pathology.

Genital infection causes severe reproductive pathologies such as salpingitis and pelvic inflammatory disease that can lead to tubal factor infertility. MicroRNAs (miRNAs) are evolutionarily conserved regulators of mammalian gene expression in development, immunity and pathophysiologic processes during inflammation and infection, including infection. Among the miRNAs involved in regulating host responses and pathologic outcome of infection, we have shown that miR-378b was significantly differentially expressed during primary infection and reinfection. In this study, we tested the hypothesis that miR-378b is involved in the pathological outcome of infection. We developed miR-378b knockout mice (miR-378b) using Crispr/Cas and infected them along with their wild-type (WT) control with to compare the infectivity and reproductive pathologies. The results showed that miR-378b mice were unable to clear the infection compared to WT mice; also, miR-378b mice exhibited a relatively higher burden throughout the duration of infection. However, gross pathology results showed that miR-378b mice had significantly reduced uterine dilatations and pathologic lesions after two infections compared to WT mice. In addition, the pregnancy and fertility rates for infected miR-378b mice showed protection from -induced infertility with fertility rate that was comparable to uninfected WT mice. These results are intriguing as they suggest that miR-378b is important in regulating host immune responses that control Chlamydial replication and drive the inflammation that causes complications such as infertility. The finding has important implications for biomarkers of Chlamydial complications and targets for prevention of disease.