Oral Presentation ESA-SRB Conference 2015

Paternal miR146a influences the female post-coital inflammatory response to seminal fluid (#6)

Hon-yeung Chan 1 , John Schjenken 1 , Sarah Robertson 1
  1. Robinson Research Institute & School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, 5005, Australia

Exposure to seminal fluid at coitus induces the expression of cytokines and chemokines in the female reproductive tract, which activates and recruits immune cells including dendritic cells, macrophages and T-regulatory (Treg) cells. These cells are crucial for implantation and the establishment of feto-maternal immune tolerance. Signalling factors in seminal fluid, including transforming growth factor beta (TGFβ) and prostaglandin-E (PGE) have been identified but studies suggest there are, as yet unidentified signalling molecules. Our recent studies have suggested that microRNAs (miRNAs) may contribute to the seminal fluid signalling cascade. One miRNA of interest, miR146a, is induced post-coitus and is carried by sperm. This miRNA regulates Treg cell functions, targets the Nf-kb inflammatory pathway and may contribute to spermatogonial differentiation and PGE production. We hypothesised that sperm derived miR146a is delivered to the female tract at coitus and influences the post-coital inflammatory response. The expression levels of miR146a and seminal fluid-induced cytokines were examined by qPCR in the endometrium of unmated estrus CBA x C57Bl/6 F1 (CBAF1) female mice, or CBAF1 females 8 hours after mating with either miR146a+/+ or miR146a-/- males (n=9-12 per group). Paternal miR146a deficiency did not alter miR146a expression in the endometrium following coitus, compared with miR146a+/+ mated group. Despite this, the absence of paternal miR146a resulted in a significant decrease in the expression of the key peri-conception cytokines Csf2, Csf3, Il1b, Il6, Tnfa and Lif and a significant increase in Ccl21a and Il10 expression compared to miR146a+/+ mated females. These findings demonstrate that while paternal miR146a is not delivered to the female tract at coitus, the absence of this miRNA in seminal fluid may alter the post-coital inflammatory response. Future studies are required to determine how cytokines are regulated by paternal miR146a and whether paternal miR146a deficiency may lead to altered pregnancy outcomes and offspring development.