Assessment of the vaginal residence time of biomarkers of semen exposure

Abstract

Objective The primary objective of this pilot study is to determine and compare the residence time in the vagina of biomarkers of semen exposure for up to 15 days post exposure. The biomarkers are prostate-specific antigen (PSA), Y chromosome DNA, the sex determining region of the Y chromosome (SRY) and testis-specific protein Y-encoded 4 (TSPY4). The secondary objectives are to determine if biomarker concentrations differed between intercourse and inoculation groups, to establish whether the sampling frequency post exposure affected biomarker concentrations and decay profile and to determine if biomarker concentrations in vaginal swabs obtained by the participant at home were similar to swabs obtained by the nurse in the clinic. Study design We randomized healthy women to unprotected intercourse (n=17) versus vaginal inoculation with the male partner’s semen in the clinic (n=16). Women were then further randomized to have vaginal swabs obtained at either 7 or 4 time points after semen exposure, up to 15 days post exposure, either obtained at home by the participant or in the clinic by the research nurse. Results PSA and SRY were markers of recent semen exposure. TSPY4 was detectable in approximately 50% of participants at 15 days post exposure. Unprotected intercourse resulted in significantly higher concentrations of select biomarkers. Sampling frequency and home versus clinic sampling had no significant effect on biomarker concentrations. Conclusions Objective biomarkers of recent or distant semen exposure may have great utility for verifying protocol compliance in a variety of clinical trials.

A longitudinal analysis of the vaginal microbiota and vaginal immune mediators in women from sub-Saharan Africa

“…The incident BV group included HIV-negative adult women (N = 16 Kenya, N = 11 South Africa), adolescents (N = 5 Kenya, N = 2 South Africa), pregnant women (N = 1 Kenya, N = 3 South Africa); and HIV-negative sex workers (N = 2 Rwanda). The detection of prostate-specific antigen (PSA) in the vagina as a marker of vaginal sex in the last 24–48 hours 23 , 24 and self-reported vaginal cleansing in the evening or morning just prior to the study visit were both common (25–57% and 28–53% at different visits, respectively). Clinician-observed abnormal vaginal discharge and cervical mucus were also common, but cervical epithelial findings visible by the naked eye (abrasion, laceration, ecchymosis, petechiae, erythema, or ulcer) were uncommon (occurring in 1–8 women at each visit), throughout the study (Table 1 ).…”

“…All models included one VMB bacteria as the outcome and individual women as random effects. We added the following fixed effects: sampling in the luteal (visits 2 and 4) versus follicular phase (visits 1, 3 and 5) of the menstrual cycle, the absence (amenorrhoea due to progestin-injectable use) or presence of a menstrual cycle (either a natural cycle or regular withdrawal bleeds during combined contraceptive use), presence of PSA as a marker of sex within the last 24–48 hours 23 , 24 , and recent vaginal cleansing (the evening or morning just prior to the study visit).…”

The Impact of Semen Exposure on the Immune and Microbial Environments of the Female Genital Tract

“…Here we investigated the impact of semen exposure on biomarkers of inflammation associated with HIV acquisition in women. YcDNA detection in female genital specimens was used as a biomarker of semen exposure within 15 days of genital sampling (31)(32)(33). YcDNA detection at the FGT predicted significantly higher levels of 11/48 cytokines, and with reduced concentrations of two, IL-18, and MIF.…”

“…Considering the potential unreliability in self-report of condom use, given that 31% of women who reported consistent condom use also had YcDNA evidence of recent condomless sex ( Table 1), we determined whether a biomarker of semen exposure may be a better indicator of immune alterations at the FGT in response to semen. YcDNA detection within female genital specimens was used as a biomarker of semen exposure within 15 days prior to genital sampling (31)(32)(33). Linear mixed models were used to compare cytokine concentrations over time and linear regression models were used to compare MMP/TIMP concentrations at baseline between women with detectable YcDNA (semen exposure) and those without (no detectable semen exposure).…”

“…Routine objective screening for the presence of semen biomarkers as opposed to self-reports of condom use may be useful to reliably assess the frequency of condomless sex e.g., during HIV prevention trials, to assess mucosal immunity to STIs, and to further characterize the impact of semen on the FGT in the context of HIV. Y-chromosome DNA (YcDNA) detection in female genital specimens has previously been used as a reliable biomarker of semen exposure within 15 days of sampling (31)(32)(33)(34)(35)(36)(37). Ychromosome polymerase chain reaction (PCR) is a highly stable, sensitive, and specific method to detect spermatozoa-associated deoxyribonucleic acid (DNA) fragments of the sex-determining region and testis-specific protein Y-encoded (TSPY) genes of the Y-chromosome that are not present on the X-chromosome gene (36,(38)(39)(40)(41).…”