Placental ageing has been associated with the pathogenesis of several complications of pregnancy including preterm birth, post-date pregnancies and stillbirth. However, the molecular mechanisms behind this are not fully understood. Alterations in the placenta associated with telomere attrition, DNA binding, genomic instability, epigenetic alterations, proteostasis, inflammation, mitochondrial dysfunction and cellular senescence have been linked with pregnancy pathologies. The aim of this study was to investigate the multifaceted role of aging in pre-term, term and post-term delivered placentae to identify specific genetic markers of ageing.
Human placenta samples (n=32) were collected from Gold Coast University Hospital, Queensland, Australia. Placental RNA was extracted and reverse transcribed using establish methods. A total of 24 genes were analysed by qPCR covering 8 areas of interest including markers of telomere attrition and DNA binding (POT1, TERF1, TERF2, EP300), genomic instability and epigenetic alterations (BUB1B, POLMRT, TFAM, TFB1M, TFB2M, ARID1A), mitochondrial dysfunction and cellular senescence (SIRT1, SIRT3, CDKN1C, VWA5A, WRN), as well as proteostasis and inflammation (FOXO1, HSF1, AIF, HSP70, TOLLIP).
Gene expression of SIRT1, TERF1, EP300 CDKN1C, FOXO1, TOLLIP and TFAM was significantly reduced in post-term placentae when compared with control tissue (p<0.05). In addition, an increase in VWA5A gene expression was identified within post-term placenta (p<0.05).
The changes in gene expression within the 8 areas of interest identifies that genes associated with mitochondrial dysfunction, cellular senescence and genomic stability were differentially expressed in aged placenta. These outcomes may help to understand the link between placental ageing and the role it plays in pregnancy pathologies.