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

Myometrium Transition to Labour-Like Phenotype: An Ex-Vivo Model For Human labour.  (#471)

Anna Paredes Barreda 1 2 , Marina Paul 1 2 , Tamas Zakar 1 2 3 , Amy Gregson 1 2 , Madeline King 1 2 , Richard Kahl 1 2 , Rohan R Walker 1 2 , Roger Smith 1 2 3 , Jonathan W Paul 1 2
  1. The university of Newcastle, Newcastle
  2. Hunter Medical Research Institute, Newcastle
  3. Hunter New England Health, Newcastle

Introduction: The myometrium (uterine smooth muscle) remains relaxed throughout fetal gestation. Approaching term, undergoes a phenotypic transformation leading to labour onset. This coincides with increased expression of contraction-associated-proteins (CAPs) and decreased expression of relaxation-associated-proteins (RAPs), which promote the contractions to deliver the fetus. We don't understand the biochemical signalling pathways that occur during this transition to a labouring phenotype. An ex vivo model for the onset of human labour can expand our knowledge.

Aims: This study aimed to assess whether non-labouring pregnant human myometrium in culture undergoes a phenotypic transformation that is consistent with transitioning toward a labour-like phenotype.

Methods: Biopsies of term, pregnant not-in-labour human myometrium were collected and a small portion snap-frozen and then stored at -80ºC. This sample represented the fresh (0 h) time point. The remaining tissue was dissected into small pieces (explants) and washed in PBS to remove blood. The explants were then incubated for 48 h in free-serum media in a humidified incubator at 37ºC, 5% CO2. After the incubation, the explants were snap-frozen and mRNA extracted. The expression of key CAPs and RAPs was determined by qRT-PCR and then compared between Fresh (0 h) versus 48 h cultured myometrium. Data were analysed by ANOVA using GraphPad Prism. 

Results: The myometrial expression of numerous RAP-encoding genes significantly decreased across 48 h culture, meanwhile, the expression of numerous CAP-encoding genes significantly increased. It has been confirmed at the protein level.

Conclusion: We observed upregulated expression of CAP-encoding genes and downregulated expression of RAP-encoding genes that are consistent with the gene expression changes that occur with term labour onset in-vivo. These gene expression changes suggest that when the term not-in-labour myometrium is cultured ex vivo, the tissue transitions to a labour-like state, making this an ex vivo model for the onset of human labour.