Regulation of seminal fluid-induced leukocyte recruitment by cytokine and chemokine expression in the human cervix after coitus (#292)
In women, transmission of seminal fluid at coitus induces infiltration of macrophages, dendritic cells and memory T cells into the cervical stroma. This is attributable to direct interactions between the seminal fluid and the cervical tissue, since use of a condom prevents the leukocytic response. To understand the molecular regulation of leukocyte recruitment observed, we investigated whether exposure to semen at coitus alters the expression of cytokines and chemokines in the cervix. Affymetrix microarray analysis and qPCR was employed using RNA prepared from ectocervical tissue obtained from women in the peri-ovulatory period and again 48 h later, 12 h after unprotected vaginal coitus, condom-protected vaginal coitus, or no coitus. Microarray analysis revealed 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. qPCR analysis confirmed that expression of several cytokine mRNAs were significantly increased by semen exposure after unprotected coitus, including CSF2 (2.5-fold), IL6 (2.6-fold), IL8 (17.3-fold) and IL1A (3.5-fold) expression. We conclude that seminal fluid introduced at intercourse elicits expression of pro-inflammatory cytokines and chemokines and in turn, these factors are implicated in controlling the ensuing leukocyte recruitment. 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 and may be relevant to transmission of sexually transmitted pathogens, and potentially also susceptibility to cervical metaplasia.