ABSTRACT: In mice, seminal fluid elicits an inflammation-like response in the female genital tract that activates immune adaptations to advance the likelihood of conception and pregnancy. Here we examined whether similar changes in leukocyte and cytokine parameters occur in the human cervix in response to the male partner’s seminal fluid. After a period of abstinence in proven-fertile women, duplicate sets of biopsies were taken from the ectocervix in the peri-ovulatory period and again 48 h later, 12 h after unprotected vaginal coitus, vaginal coitus with use of a condom, or no coitus. One pair of first biopsy and second biopsy RNA samples from each treatment group were reverse transcribed into cDNA and hybridized to Affymetrix Human Gene 1.0 ST arrays. A total of 713 probe sets were identified as differentially expressed (fold change >2) between first and second biopsies after unprotected coitus, with 436 genes upregulated and 277 genes downregulated. Ingenuity Pathway Analysis revealed that gene pathways including inflammatory response, immune response, immune cell trafficking, cellular movement and antigen presentation were significantly affected by seminal fluid exposure. Amongst these were genes encoding several chemokines which target granulocytes, monocyte/macrophages, dendritic cells and lymphocytes, proinflammatory cytokines and regulators of cytokine synthesis, prostaglandin pathway gene including PTGS2; COX-2) and several matrix metalloproteinases (MMPs). Of these genes, no change or a substantially smaller change was seen between first and second biopsies obtained after coitus with condom use, or abstinence. An increase in CSF2, IL6, IL8 and IL1A expression was confirmed by qRT-PCR in larger sets of duplicate biopsies (n=6-7 per group). We conclude that seminal fluid introduced at intercourse elicits expression of pro-inflammatory cytokines and chemokines which underpins the accompanying recruitment of macrophages, dendritic cells and memory T cells. The leukocyte and cytokine environment induced in the cervix by seminal fluid appears competent to initiate adaptations in the female immune response that promote fertility. This response is also relevant to transmission of sexually transmitted pathogens, and potentially susceptibility to cervical metaplasia. Women aged 18-40 years, with regular menstrual cycles and a current sexual relationship with a proven fertile regular partner, volunteered for the study. All women had previously undergone tubal ligation and none of the women used steroidal contraceptives or an intrauterine device for a minimum of three months preceding the study. Subjects were screened to exclude bacterial or viral infection. A negative test result was a prerequisite for inclusion in the study. The study was approved by the local ethics committee of Karolinska University Hospital, Stockholm, Sweden.
