The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Paternal miR-146a regulation of male reproductive parameters and its influence on the female immune response at conception in the mouse (#109)

Hon Y Chan 1 , John E Schjenken 1 , Peck Y Chin 1 , Ricky A Matias 1 , Nicole O McPherson 1 , Sarah A Robertson 1
  1. Robinson Research Institute & Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia

Seminal fluid interacts with female uterine epithelial cells to induce pro-inflammatory cytokine and chemokine expression, which in turn promotes immune tolerance and tissue remodelling for optimal pregnancy progression. Seminal fluid signalling factors, including transforming growth factor-beta (TGFß), have been identified but additional signalling molecules remain to be discovered. Our recent studies have suggested that microRNAs (miRNAs) may contribute to seminal fluid signalling capacity. One miRNA, miR-146a, regulates factors involved in spermatogonial differentiation and TGFß signalling pathway. This study aimed to investigate the physiological role of paternal miR-146a in seminal fluid signalling capacity using miR-146a-deficient mouse strain. Female endometrial responsiveness to seminal fluid was examined by qPCR in unmated estrus BALB/c females, or in BALB/c females 8 hours following mating with miR-146a+/+ or miR-146a-/- males (n=7-11/group). Pregnancy outcomes were measured on day 17.5 post-coitum (pc) (n=28-30 pregnancies/group). Male reproductive parameters were determined after euthanasia at 6-7 months old (n=18-19). Contact with seminal fluid from miR-146a-/- males resulted in a significant decrease in endometrial expression of Cxcl2 and Il6 (49.8% decrease for both genes), compared to miR-146a+/+-mated females. Day 17.5pc analysis showed that surprisingly, miR-146a-/--male-sired litters contained an increased number of viable pups (19.3% increase compared to miR-146a+/+-male-sired litters). Fetal weight was not affected by paternal genotype, but placental weight was reduced (8.0% decrease compared to miR-146a+/+-male-sired litters). Analysis of male reproductive tract parameters revealed that miR-146a-/- males had larger seminal vesicles (11.2% increase), but produced less motile (12.8% reduction) and less sperm with normal morphology (10.2% reduction). These findings suggest that paternal miR-146a influences the nature of seminal fluid signals in such a way as to impact the strength and quality of the female response, and this is linked to higher implantation rates. Further experiments are required to elucidate the specific mechanisms by which paternal miR-146a influences seminal fluid signalling capacity.