Oral Presentation The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2017

At coitus seminal fluid activates genes associated with cholesterol biosynthesis in the endometrium of the mouse (#20)

John E Schjenken 1 , Allisha K Foster 1 , Sebastian J Hammond 1 , Carri J Welsby 1 , David J Sharkey 1 , Jimmy Breen 1 , Sarah A Robertson 1
  1. Robinson Research Institute and Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia

Seminal fluid interacts with epithelial cells lining the female reproductive tract to initiate adaptations that influence pregnancy success and contribute to subsequent fetal development and offspring health. Central to the female response to seminal fluid is the establishment of a tolerogenic immune environment. However, many genes regulated by seminal fluid are not associated with immune signalling pathways. Using Affymetrix microarray and bioinformatics analysis approaches this study aimed to identify additional regulated pathways.

Gene expression profiles were examined by Affymetrix microarray gene ST 1.0 and 2.0 microarrays from mouse endometrium collected from unmated oestrus CBAF1 females or females 8 hours following mating with either seminal vesicle deficient and vasectomised, vasectomised or intact Balb/c males (n=4 per group). Data was assessed using R/Bioconductor packages and Ingenuity Pathway Analysis software.

Seminal fluid exposure induced major changes in the gene expression profile with genes associated with immune signalling pathways presenting as a significant proportion of differentially expressed genes. In addition to immune genes, genes associated with the cholesterol biosynthesis including cytochrome P450 51a1 (Cyp51a1, lanosterol 14α-demethylase, 3.07-fold increase), lanosterol synthase (Lss, 1.72-fold increase) and hydroxysteroid 17-beta type VII (HSD17B7, 17-beta-hydroxysteroid dehydrogenase which also functions as 3-ketosteroid reductase, 2.52-fold increase) were amongst those highly up-regulated (p<0.05) following seminal fluid exposure. These endometrial gene expression changes required exposure to the complete ejaculate in an intact mating, as mating with vasectomised males had no effect.

Activation of cholesterol biosynthesis pathways by seminal fluid may be a mechanism to accumulate cholesterol for de novo synthesis of progesterone in the endometrium and may play a crucial role in implantation and maintenance of pregnancy. Future studies will confirm these findings and explore the impact of cholesterol biosynthesis on the maternal uterine environment in the peri-conception period.