Oral Virtual Presentation (Virtual only) ESA-SRB-ANZBMS 2021

Transcriptomic analysis of the seminal vesicle response to the reproductive toxicant acrylamide (#203)

David A Skerrett-Byrne 1 2 , Brett Nixon 2 3 , Elizabeth G Bromfield 2 3 4 , Jimmy Breen 5 6 7 , Natalie A Trigg 2 3 , Simone Stanger 2 3 , Ilana R Berntstein 2 3 , Amanda L Anderson 2 3 , Tessa Lord 2 3 , Robert John Aitken 1 2 , Shaun D Roman 2 3 , Sarah A Robertson 5 , John E Schjenken 1 2
  1. Priority Research Centre for Reproductive Science. School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW, Australia
  2. Pregnancy and Reproduction Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
  3. Priority Research Centre for Reproductive Science and School of Environmental and Life Sciences, University of Newcastle, Callaghan, 2308
  4. Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands
  5. Robinson Research Institute and Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia
  6. South Australian Genomics Centre (SAGC), South Australian Health & Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia
  7. Computational & Systems Biology Program, Precision Medicine Theme, South Australian Health & Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia

The seminal vesicles synthesise bioactive factors that support gamete function, modulate the female reproductive tract to promote implantation, and influence developmental programming of offspring phenotype. Despite the significance of the seminal vesicles in reproduction, their biology remains poorly defined. Here, we analysed the mouse seminal vesicle transcriptome under normal physiological conditions and in response to acute exposure to the reproductive toxicant acrylamide. Mice were administered acrylamide (25 mg/kg bw/day) or vehicle control daily for five consecutive days prior to collecting seminal vesicle tissue 72 h following the final injection. A total of 15,304 genes were identified in the seminal vesicles with those encoding secreted proteins amongst the most abundant. In addition to reproductive hormone pathways, functional annotation of the seminal vesicle transcriptome identified cell proliferation, protein synthesis, and cellular death and survival pathways as prominent biological processes. Administration of acrylamide elicited 70 differentially regulated (fold-change ≥ 1.5 or ≤ 0.67, adjusted p value ≤ 0.1) genes, several of which were orthogonally validated using quantitative PCR. Pathways that initiate gene and protein synthesis to promote cellular survival were prominent amongst the dysregulated pathways. Inflammation was a key transcriptomic response to acrylamide, with the cytokine, Colony stimulating factor 2 (Csf2) identified as a top-ranked upstream driver. Early growth response (Egr1), C-C motif chemokine ligand 8 (Ccl8), and Collagen, type V, alpha 1 (Col5a1), were also identified amongst the dysregulated genes. Additionally, acrylamide treatment led to subtle changes in the expression of genes that encode proteins secreted by the seminal vesicle, including the complement regulator, Complement factor b (Cfb). Together these findings support the interpretation that toxicant exposure influences male accessory gland physiology and highlights the need to consider the response of all male reproductive tract tissues when interpreting the impact of environmental stressors on male reproductive function.