Oral Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Sub-chronic elevation in ambient temperature drives alterations to the sperm epigenome and accelerates early embryonic development in mice (#11)

Natalie A Trigg 1 2 3 , John E Schjenken 1 2 , Jacinta H Martin 1 2 , David A Skerrett-Byrne 1 2 , Shannon P Smyth 1 2 4 , Ilana R Bernstein 1 2 , Amanda L Anderson 1 2 , Simone J Stanger 1 2 , Ewan N.A Simpson 1 2 , Archana Tomar 5 6 , Raffaelle Teperino 5 6 , Coline C Conine 3 7 , Geoffry N De Iuliis 1 2 , Shaun D Roman 8 , Elizabeth G Bromfield 1 2 4 , Matthew D Dun 9 10 , Andrew L Eamens 11 , Brett Nixon 1 2
  1. Infertility and Reproduction Program, Hunter Medical Research Institute, New Lambton Heights, NSW
  2. School of Environmental and Life Science, The University of Newcastle, Callaghan, NSW
  3. Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, USA
  4. School of BioScience, Bio21 Institute, Faculty of Science, University of Melbourne, Parkville, VIC
  5. Institute of Experimental Genetics,, German Research Center for Environmental Health, Neuherberg, Germany
  6. German Center for Diabetes Research, Neuherberg, Germany
  7. Departments of Genetics and Pediatrics, Penn Epigenetics Institute, Institute of Regenerative Medicine and Center for Reproduction and Women's Health, University of Pennsylvania, Philadelphia, USA
  8. NSW Health Pathology, Newcastle, NSW
  9. Cancer Signaling Research Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW
  10. Precision Medicine Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW
  11. School of Health, University of the Sunshine Coast, Maroochydore, QLD

Climate change models have predicted increases in global temperatures of up to 6.4°C by the end of this century1. Owing to the sensitivity of sperm production2, these trends of increasing temperature pose a high risk to the reproductive capacity of humans and animals of ecological and agricultural significance. Despite this, we lack a comprehensive understanding of the immediate impact of heat stress on male reproduction. To address this knowledge gap, we exposed unrestrained male mice to heat stress conditions that emulate a typical heatwave scenario over seven days (daily cycle of 8 h at 35°C and 16 h at 25°C) prior to assessing the immediate impact on male reproductive function and embryo development.

Through a comprehensive analysis, we determined that the imposed heat regimen did not affect sperm functionality, sperm DNA integrity or the ability of sperm to support embryonic development. However, the embryos fertilised by the spermatozoa of heat exposed males experienced pronounced changes in gene expression (430 dysregulated genes at the morula stage, P < 0.05) linked to acceleration of early embryo development (P < 0.05 at 72 h development), aberrant blastocyst hatching (4-fold increase, P < 0.01) and increased fetal weight (P < 0.05). These changes were causally associated with altered profiles of sperm small non-coding RNAs (sncRNAs), such that embryo developmental phenotypes were recapitulated by microinjection of wild-type embryos sired by control spermatozoa with RNA from heat exposed spermatozoa.

These data highlight that the sperm sncRNA profile is a particular point of vulnerability to this imposed environmental stress. Moreover, the timing of this heat exposure regimen firmly implicates stress signals encountered during epididymal transit in altering the sperm epigenome.