Discussion
inflammation
STIS, INFLAMMATION, PROLIFERATION, INFILTRATING
Although, sub-Saharan African women are at high risk for both STIs, including HIV, and unintended pregnancies, the impact of commonly used NBC methods on the mucosal immune environment has not been studied in detail using randomized designs. In this study, we examined the effects of three common and highly effective NBCs on endocervical gene expression of Kenyan and South African women enrolled into the ECHO trial, using high throughput transcriptomics.We found that women assigned to Cu-IUD had dramatic endocervical transcriptional perturbations compared to women assigned to DMPA-IM and LNG implant and that these transcriptomic changes were associated with enrichment of immune activation pathways including inflammation and anti-viral responses. Accordingly, using data from the same ECHO cohort, we have previously reported that Cu-IUD induced significant increases in cytokine concentrations six months post-insertion compared to baseline [One of the more striking findings within the Cu-IUD arm, in addition to upregulation of inflammatory and interferon-related pathways, was the significantly upregulated MT genes,. The MT1 gene family has ten known functional genes [In this study, we found that DMPA-IM initiation was associated with an enrichment of gene pathways associated with T cell responses, consistent with an enrichment of infiltrating T cells into the cervicovaginal environment. Some observational studies have associated DMPA-IM with elevated levels of cervical immune cells, including CD4+ T-cells, and increased expression of the HIV co-receptor CCR5 on these cells [In our analysis of DMPA-treated women, we also considered if the vaginal microbiome was influencing the local transcriptome based on Published data on the influence of LNG implants on the FGT transcriptome is sparse. In this study, we found limited endocervical transcriptomic alterations in women randomized to the LNG implant arm. We did however observe an enrichment of pathways associated with cell proliferation and growth and a decrease in expression of pathways associated with cell cycle control and DNA repair. These transcriptomic changes differed from those observed in the women using DMPA-IM despite both contraceptives being progestin based, highlighting the differential impact of progestins with different pharmacokinetic and pharmacodynamic properties on the FGT milieu as have been shown in vitro [