Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Male seminal fluid signalling and fertility in women (#180)

David Sharkey 1 , John E Schjenkin 1 , John J Bromfield 1 , Kelton P Tremellen 2 , Mary L Hull 1 3 , Sarah A Robertson 1
  1. Robinson Research Institute & School of Medicine, University of Adelaide, Adelaide, South Australia, Australia
  2. Repromed, Adelaide, SA, Australia
  3. Fertility SA, Adelaide, SA

Conventionally it is believed that seminal fluid had just one biological function, to aid in the delivery of spermatozoa into the female tract, thereby facilitating fertilisation of the oocyte. In the past two decades, it has been demonstrated that seminal fluid has a far more complex function in reproductive events. It contains an abundance of signalling agents, capable of interacting with female tract tissues and influencing female reproductive physiology.. In rodents, these signalling agents have been shown to induce inflammatory changes within the female tract necessary for the priming of the immune response to paternal antigens, critical for establishing maternal immune tolerance for successful embryo implantation and optimal placental development. Emerging evidence suggests comparable effects in women, where exposure of the female tract to the male partner’s seminal fluid induces marked changes in cytokine and chemokine production and subsequent leukocyte recruitment within the cervical tissue. Microarray analysis has revealed this inflammatory response is characterised by increased expression of several pro-inflammatory cytokines including CSF2, IL6, as well as the chemokines CXCL8 and CCL2, followed by recruitment of macrophages, dendritic cells, granulocytes and lymphocytes into the cervical tissue. Remarkably, we have recently demonstrated using endometrial biopsies collected before and after intercourse, that the effects of seminal fluid exposure appears to extend to the higher female tract, with microarray analysis revealing changes in cytokine and chemokine gene expression comparable to those observed in the cervical tissues, occurring within the endometrium. Our laboratory has also focused on determining the identity of signalling agents in human seminal fluid, with members of the TGFB superfamily, including the three mammalian isoforms of TGFB, Activin A and Follistatin identified as key mediators of this response that signal induction of pro-inflammatory cytokine synthesis in cervical cells. Additional active factors in seminal fluid include hydroxylated forms of prostaglandin E, namely 19-OH PGE1 and 19-OH PGE2. Our recent studies demonstrate considerable fluctuations within individual men, as well as between men, in these signalling agents.  Differences in the endogenous cytokine composition of men, potentially resulting from environmental inflammatory exposures such as smoking or infection, may alter the inflammatory response elicited within the female partner tissues following coitus, with implications for tolerance to paternal antigens, fertility and incidence of preeclampsia and related pregnancy disorders.