The impact of semen exposure on cytokine response and bacterial vaginosis in the female genital tract.

Master of Medical Sciences. University of Kwa-Zulu Natal. Durban, 2018.Background: Diverse microbial communities and inflammatory cytokine responses in the lower female genital tract (FGT) are closely associated with increased human immunodeficiency virus (HIV-1) risk, possibly through increasing mucosal HIV target cell frequency and T-cell activation. The presence of semen in the vagina during unprotected sex has been associated with short-term activation of mucosal immunity. Here, we investigated the extent to which partner semen impacts on cytokine and microbial profiles measured in 248 HIV-uninfected women at high risk for HIV infection. Methods: We assessed the semen exposure in SoftCup supernatants by quantifying prostate specific antigen (PSA) levels using enzyme-linked immunosorbent assay (ELISA). Luminex was used to measure 48 cytokines in SoftCup supernatants and the vaginal swabs were used for diagnosis of bacterial vaginosis by Nugent score. Results: PSA, which denotes semen exposure within 48 hours prior to sampling, was detected in 19% (43/248) of SoftCup supernatants. Of the 43 PSA positive women, 70% (30/43) had self-reported condom use at their last sex act and 84% (36/43) had non-Lactobacillus dominant microbiota (Nugent score >7). In addition, PSA was significantly associated with prevalent bacterial vaginosis (Relative Risk (RR), 2.609; 95% Confidence Interval (CI), 1.104 - 6.165; p = 0.029), after adjusting for potential confounders such as age, STIs, current contraceptive use and condom use. Furthermore, women with detectable PSA had high median concentrations of Macrophage inflammatory protein- beta (MIP-1β) (p=0.047) compared to those without PSA. Conclusion: These findings suggest that the presence of semen has a potential to alter the inflammatory response and microbial communities of the FGT, which may facilitate recruitment of HIV susceptible cells, resulting in increased susceptibility to HIV-1 infection

Recent Semen Exposure Impacts the Cytokine Response and Bacterial Vaginosis in Women

BackgroundThe presence of semen in the vagina from unprotected sex may influence the immune and microbial environment of the female genital tract. Inflammatory cytokine concentrations and BV-associated bacteria in female genital secretions may influence HIV risk, although the effect of recent sexual intercourse on incident BV and the cytokine milieu of cervicovaginal secretions has rarely been measured in previous studies. Here, we investigated the extent to which partner semen impacts the cytokine response and incident BV.MethodsAt baseline, we assessed the recency of semen exposure in menstrual cup supernatants by quantifying prostate specific antigen (PSA) levels using ELISA in 248 HIV-uninfected women at high risk for HIV infection. Luminex was used to measure 48 cytokines in menstrual cup supernatants and vaginal swabs to diagnose BV by Nugent score. Point-of-care screening for Chlamydia trachomatis and Neisseria gonorrhoeae was conducted using GeneXpert while OSOM was used for Trichomonas vaginalis detection. Multivariable models, adjusted for age, sexually transmitted infections, BV, current contraception use and condom use, were used to assess the impact of semen exposure on biomarkers of inflammation and BV.ResultsPresence of PSA, indicating recent semen exposure within 48 hours prior to sampling, was observed in menstrual cup supernatants of 17% (43/248) of women. Of these women, 70% (30/43) had self-reported condom use at their last sex act and 84% (36/43) had BV (Nugent score >7). PSA presence was significantly associated with prevalent BV (Relative Risk (RR), 2.609; 95% Confidence Interval (CI), 1.104 - 6.165; p = 0.029). Furthermore, women with detectable PSA had high median concentrations of macrophage inflammatory protein- beta (MIP-1α, p=0.047) and low median concentration of the stem cell growth factor beta (SCGF-β, p=0.038) compared to those without PSA.ConclusionA degree of discordance between self-reports of consistent condom use and PSA positivity was observed. There was also evidence of a relationship between recent semen exposure, BV prevalence and altered cytokine concentrations. These findings suggest that PSA, as a semen biomarker, should be taken into consideration when investigating biological markers in the female genital tract and self-reported condom use in studies on reproductive and sexual health